February 26, 2009 — The incidence of 2 severe autoimmune cytopenias — immune thrombocytopenia purpura (ITP) and autoimmune hemolytic anemia (AIHA) — has been shown to be elevated among individuals infected with hepatitis C virus (HCV). Research published in the February 23 issue of the Archives of Internal Medicine reveals that HCV-infected patients in the Veterans Affairs (VA) health system were at increased risk of developing ITP. However, those who underwent treatment were also at increased risk for AIHA.
"Prior studies suggesting that HCV might be an etiologic risk factor for the development of autoimmune cytopenias have been based on small series of patients from single institutions," write Elizabeth W. Chiao, MD, MPH, from the Department of Medicine, Baylor College of Medicine, Houston, and the Houston Center for Quality of Care and Utilization Studies, Health Service Research and Development Service, Michael E. DeBakey Veterans Affairs Medical Center, Texas, and colleagues. "To our knowledge, no large study has been conducted. Given that US military veterans have a high prevalence of HCV infection (5%), this population provides a unique opportunity to observe HCV-related phenomena."
To determine the effect of HCV infection on the incidence rates of ITP and AIHA, researchers analyzed the inpatient and outpatient records as well as pharmacy data from HCV-infected (n = 120,691) and matched uninfected (n = 454,905) veterans. The diagnosis of ITP and AIHA was identified via hospitalization codes. Those with a prior diagnosis of lymphoproliferative disease, HIV, or cirrhosis were excluded from the analysis.
"In this large national cohort study including over half a million US veterans, we observed HCV-infected persons to be at increased risk of ITP and AIHA," explain the authors. A Cox proportional hazards regression model revealed that the hazard ratios (HRs) for ITP and AIHA were 1.8 (95% confidence interval [CI], 1.4 – 2.3) and 2.8 (95% CI, 1.8 – 4.2), respectively.
"Because both ITP and AIHA have been previously associated with interferon alfa use, we were also interested in assessing pharmacy data to account for the effects of HCV treatment," write Dr. Chiao and colleagues. While the incidence of ITP was elevated among both treated and untreated HCV-infected individuals, the incidence of AIHA was only elevated among those who had received treatment (HR, 11.6; 95% CI, 7.0 – 19.3).
These findings were further illustrated by examining the Kaplan-Meier curves of the cumulative incidence of each of the outcomes. The cumulative incidence of ITP was significantly greater among HCV-infected individuals vs matched control individuals (P < .001) and remained significant following censorship at the time of treatment (log rank test; P = .002). However, the cumulative incidence of AIHA was significantly greater among HCV-infected individuals vs matched control individuals (P < .001), but this difference was no longer significant following censorship at the time of treatment (log rank test; P = .84).
The main advantage of this study is that it is the first involving a large cohort to evaluate the effect of HCV infection on autoimmune cytopenias. However, there were several potential limitations. These included that the diagnoses of ITP and AIHA were not confirmed through a review of the medical records; that the calculation of the cumulative incidence of ITP and AIHA did not take into consideration other competing risks, which could have resulted in biased estimates; that the study involved a relatively short follow-up, which resulted in fewer ITP and AIHA events, thereby limiting the power to detect differences; that the incidence rates of ITP and AIHA in this study were higher than the incidence rates previously reported for the general population; that the HCV genotype or the rates of sustained virologic response after treatment were not confirmed via laboratory data; that there was a limited ability to account for bias introduced by other factors, which resulted in patients being excluded from treatment based on their physician's decision; and last, that the study population was made up almost entirely (96.5%) of men.
Several biological mechanisms have been suggested to explain the relationship between HCV infection and the development of ITP. The current findings illustrate that chronic HCV infection may cause ITP via a platelet-specific mechanism in addition to the occurrence of generalized autoimmunity. Thus, the researchers suggest that the term "HCV-associated thrombocytopenias" may be appropriate for future studies. Furthermore, interferon alfa has previously been associated with ITP and AIHA. The results of this study reinforce the theory that immunomodulatory effects of interferon alfa many cause an increased risk for autoimmune cytopenia.
"Future research is needed to clarify the underlying mechanisms and implications of our findings," conclude the authors.
This study was supported by the Intramural Program of the National Cancer Institute, National Institutes of Health, and the Houston VA Health Services Research and Development Center of Excellence. The authors have disclosed no relevant financial relationships.
Arch Intern Med. 2009;169:357–363.
Saturday, March 21, 2009
Alcohol, Hepatitis C: Dangerous Cocktail
Patients infected by the virus can develop liver cancer if they drink too much liquor, Keck School researchers find.
A new study led by researchers at the Keck School of Medicine of USC found that drinking alcohol greatly increases the chances that a patient infected by the hepatitis C virus will develop a common type of liver cancer.
The study appeared in the Proceedings of the NationalAcademy of Sciences.
The research clarifies the complex molecular events that link alcoholism and the virus to increased risk of hepatocellular carcinoma HCC, the fifth most common cancer worldwide, according to Keigo Machida, assistant professor of molecular microbiology and immunology at the Keck School of Medicine.
There is ample evidence that chronic liver damage caused by viral infection, alcohol, metabolic syndrome or these factors in combination can increase the risk for the virus, Machida said. However, the molecular mechanism for the synergy among alcohol, the virus and liver cancer has remained unclear.
“Understanding the molecular link holds great potential for future treatment of this particular form of liver cancer,” Machida said. “The signaling mechanism gives researchers a new drug therapy target for treating HCC.”
Machida and his colleagues focused their research on a viral protein, NS5A, which in earlier experiments stimulated high expression of a receptor for bacterial endotoxins, known as Toll-like receptor 4 (TLR4). Alcohol intake increases the risk of leaking bacterial toxin from the gut, which the researchers believe causes over-activation of endotoxin receptor signaling if patients are also infected by hepatitis C virus.
This excess antibacterial reaction then results in an increased risk of tumor growth should the body’s natural anti-tumor response weaken as a result of the infection, Machida explained.
Researchers conducted a series of experiments with mice and also examined liver biopsy samples from human patients infected with the virus and found high levels of the protein NS5A and TLR4. In the subset of patients who were also alcoholics, the researchers saw signs of increased antibacterial response. The research also identified a specific molecule called Nanog, which acts as a stem cell marker in tumor development when activated by TLR4.
“There were several major findings that resulted from this study,” Machida said. “We established a mouse model which will enable us to better understand alcohol and hepatitis C virus infection, and we found the signaling that causes tumor development in mice through the receptor TLR4.”
“More research is needed, but if we are able to target and suppress these molecules identified in the study, we may be able to stop the cancer’s lifeline.
A new study led by researchers at the Keck School of Medicine of USC found that drinking alcohol greatly increases the chances that a patient infected by the hepatitis C virus will develop a common type of liver cancer.
The study appeared in the Proceedings of the NationalAcademy of Sciences.
The research clarifies the complex molecular events that link alcoholism and the virus to increased risk of hepatocellular carcinoma HCC, the fifth most common cancer worldwide, according to Keigo Machida, assistant professor of molecular microbiology and immunology at the Keck School of Medicine.
There is ample evidence that chronic liver damage caused by viral infection, alcohol, metabolic syndrome or these factors in combination can increase the risk for the virus, Machida said. However, the molecular mechanism for the synergy among alcohol, the virus and liver cancer has remained unclear.
“Understanding the molecular link holds great potential for future treatment of this particular form of liver cancer,” Machida said. “The signaling mechanism gives researchers a new drug therapy target for treating HCC.”
Machida and his colleagues focused their research on a viral protein, NS5A, which in earlier experiments stimulated high expression of a receptor for bacterial endotoxins, known as Toll-like receptor 4 (TLR4). Alcohol intake increases the risk of leaking bacterial toxin from the gut, which the researchers believe causes over-activation of endotoxin receptor signaling if patients are also infected by hepatitis C virus.
This excess antibacterial reaction then results in an increased risk of tumor growth should the body’s natural anti-tumor response weaken as a result of the infection, Machida explained.
Researchers conducted a series of experiments with mice and also examined liver biopsy samples from human patients infected with the virus and found high levels of the protein NS5A and TLR4. In the subset of patients who were also alcoholics, the researchers saw signs of increased antibacterial response. The research also identified a specific molecule called Nanog, which acts as a stem cell marker in tumor development when activated by TLR4.
“There were several major findings that resulted from this study,” Machida said. “We established a mouse model which will enable us to better understand alcohol and hepatitis C virus infection, and we found the signaling that causes tumor development in mice through the receptor TLR4.”
“More research is needed, but if we are able to target and suppress these molecules identified in the study, we may be able to stop the cancer’s lifeline.
Liver transplant recipients with hepatitis B may need lifelong antiviral treatment
Patients who undergo liver transplantation for hepatitis B-related liver damage should receive lifelong antiviral treatment to keep the disease from coming back. A new study shows that they lack cellular immunity against the disease, making recurrence likely if antiviral treatment is withdrawn. These findings are in the March issue of Liver Transplantation.
Chronic hepatitis B (HBV) is a common cause of advanced liver disease and liver cancer. Liver transplantation is the most effective treatment, however, without ongoing antiviral therapy, HBV recurs in 80 percent of recipients. While the patient's immune system plays a critical role in both viral clearance and liver injury, the role of HBV-specific cellular immunity in liver transplant patients has been unclear.
Researchers, led by Chung Mau Lo, of The University of Hong Kong, set out to understand this immunity in patients with HBV who received a liver transplant. They examined HBV-specific CD4 T-cell immune response in 52 HBV patients who'd undergone liver transplantation. Forty of these patients had experienced HBV recurrence and 12 had not. They compared data from 63 people with HBV who had not undergone transplantation. Forty such patients had chronic HBV and 23 had self-limited infection.
Researchers introduced HBV-encoded antigens to blood samples from each patient. They then determined T-cell proliferation and interferon-γ production in vitro. They found that cellular immunity in transplant recipients with recurrence was not significantly different from that of chronically infected individuals with elevated aminotransferases. However, transplant patients without recurrence had lower or undetectable CD4 T-cell response.
"Our results provide strong evidence to support the concept that the CD4 T cell-mediated immune response is an antigen-driven process," the authors report.
An accompanying editorial by Anne Marie Roque-Afonso of Hopital Paul Brousse in France suggests that the study points to the need for indefinite antiviral therapy in liver transplant recipients with HBV, due to their lack of anti-HBV immunity.
"Immunosuppression following liver transplantation for HBV-related disease presents the maximal risk of viral reactivation and mandates life-long prophylaxis," she concludes.
Source: Wiley
Chronic hepatitis B (HBV) is a common cause of advanced liver disease and liver cancer. Liver transplantation is the most effective treatment, however, without ongoing antiviral therapy, HBV recurs in 80 percent of recipients. While the patient's immune system plays a critical role in both viral clearance and liver injury, the role of HBV-specific cellular immunity in liver transplant patients has been unclear.
Researchers, led by Chung Mau Lo, of The University of Hong Kong, set out to understand this immunity in patients with HBV who received a liver transplant. They examined HBV-specific CD4 T-cell immune response in 52 HBV patients who'd undergone liver transplantation. Forty of these patients had experienced HBV recurrence and 12 had not. They compared data from 63 people with HBV who had not undergone transplantation. Forty such patients had chronic HBV and 23 had self-limited infection.
Researchers introduced HBV-encoded antigens to blood samples from each patient. They then determined T-cell proliferation and interferon-γ production in vitro. They found that cellular immunity in transplant recipients with recurrence was not significantly different from that of chronically infected individuals with elevated aminotransferases. However, transplant patients without recurrence had lower or undetectable CD4 T-cell response.
"Our results provide strong evidence to support the concept that the CD4 T cell-mediated immune response is an antigen-driven process," the authors report.
An accompanying editorial by Anne Marie Roque-Afonso of Hopital Paul Brousse in France suggests that the study points to the need for indefinite antiviral therapy in liver transplant recipients with HBV, due to their lack of anti-HBV immunity.
"Immunosuppression following liver transplantation for HBV-related disease presents the maximal risk of viral reactivation and mandates life-long prophylaxis," she concludes.
Source: Wiley
U.S. Panel Widens Recommendations on Hepatitis A Vaccination
CHICAGO (Reuters) Feb 25 - U.S. citizens who expect to have close contact with an adopted child from countries with high rates of hepatitis A should be immunized if they have not been already, U.S. immunization advisers said on Wednesday.
The Advisory Committee on Immunization Practices, which advises the U.S. Centers for Disease Control and Prevention, said unvaccinated people who will have close contact with the child should get the vaccine within 60 days of the adoptee's arrival in the United States.
Prior recommendations covered only parents traveling to countries with high or intermediate rates of hepatitis A infection.
Last year, the CDC received several reports of hepatitis A infections in children and adults linked to adoptees from Ethiopia.
The committee, meeting in Atlanta, said adoptive parents and caregivers should get the first dose of the hepatitis A vaccine as soon as adoption is planned.
Ideally, the first of two doses of the vaccine should be administered at least two weeks before the child's arrival.
The CDC recommends vaccination for all children starting at age 1, for travelers to certain countries and others at risk.
The Advisory Committee on Immunization Practices, which advises the U.S. Centers for Disease Control and Prevention, said unvaccinated people who will have close contact with the child should get the vaccine within 60 days of the adoptee's arrival in the United States.
Prior recommendations covered only parents traveling to countries with high or intermediate rates of hepatitis A infection.
Last year, the CDC received several reports of hepatitis A infections in children and adults linked to adoptees from Ethiopia.
The committee, meeting in Atlanta, said adoptive parents and caregivers should get the first dose of the hepatitis A vaccine as soon as adoption is planned.
Ideally, the first of two doses of the vaccine should be administered at least two weeks before the child's arrival.
The CDC recommends vaccination for all children starting at age 1, for travelers to certain countries and others at risk.
Liver Tumors Associated With Metabolic Syndrome Differ From Other Tumors
ScienceDaily (Feb. 25, 2009) — Liver cancer in patients whose only risk factor is metabolic syndrome has distinct forms and structures compared to other liver tumors.
Cancer of the liver, also known as hepatocellular carcinoma, is the fifth most common type of cancer in the world. It is increasing in incidence, largely due to the spread of hepatitis C. Its growing prevalence may also be related to the rise of obesity and type-2 diabetes, which are associated with non-alcoholic fatty liver disease (NAFLD). However, liver cancers associated with NAFLD have been poorly described.
Researchers, led by Valerie Paradis of Beaujon hospital in Paris, decided to analyze a series of liver cancers which arose in patients whose only risk factor for chronic liver disease was metabolic syndrome. They compared their findings to the characteristics of hepatocellular carcinomas that developed in the setting of other chronic liver diseases.
Their retrospective analysis included 128 patients in their hospital who had undergone surgery to remove a liver tumor between 1995 and 2007. Of these, 81 patients had an overt cause of chronic liver disease (CLD), like hepatitis B or hepatitis C. Thirty-one patients had features of the metabolic syndrome (MS) as their only risk factor. And sixteen patients had no identifiable risk factors.
“Most hepatocellular carcinoma associated with features of metabolic syndrome as the only risk factor for chronic liver disease develop in non-fibrotic liver,” the authors report. They found that just over 35 percent of liver tumors in these patients occurred in bridging fibrosis or cirrhosis, compared to 75 percent in the patients with chronic liver disease.
“Our results suggest that well-recognized multistep progression, i.e. fibrosis-cirrhosis-HCC, may not be the main carcinogenic pathway in the context of metabolic syndrome,” they write. They suggest that the metabolic syndrome itself could have a direct cancer-causing effect, perhaps through the effects of insulin, lipid peroxidation or free radical oxidative stress.
They noted that most tumors arising in the context of the metabolic syndrome were well differentiated – nearly 65 percent compared to 28 percent in the patients with chronic liver disease. These tumors were more similar to those in patients with tumors from unknown causes, which also had better differentiation and a low prevalence of significant fibrosis.
Interestingly, the researchers found that among the patients with metabolic syndrome, five cases of liver cancer were associated with liver cell adenoma (a benign liver tumor).
“Our results suggest that a significant percentage of hepatocellular carcinoma that developed in the context of metabolic syndrome without significant fibrosis arose from malignant transformation of liver cell adenoma,” they report.
Journal reference:
Paradis et al. Hepatocellular carcinomas in patients with metabolic syndrome often develop without significant liver fibrosis: A pathological analysis. Hepatology, 2009; 49 (3): 851 DOI: 10.1002/hep.22734
Adapted from materials provided by Wiley-Blackwell.
Cancer of the liver, also known as hepatocellular carcinoma, is the fifth most common type of cancer in the world. It is increasing in incidence, largely due to the spread of hepatitis C. Its growing prevalence may also be related to the rise of obesity and type-2 diabetes, which are associated with non-alcoholic fatty liver disease (NAFLD). However, liver cancers associated with NAFLD have been poorly described.
Researchers, led by Valerie Paradis of Beaujon hospital in Paris, decided to analyze a series of liver cancers which arose in patients whose only risk factor for chronic liver disease was metabolic syndrome. They compared their findings to the characteristics of hepatocellular carcinomas that developed in the setting of other chronic liver diseases.
Their retrospective analysis included 128 patients in their hospital who had undergone surgery to remove a liver tumor between 1995 and 2007. Of these, 81 patients had an overt cause of chronic liver disease (CLD), like hepatitis B or hepatitis C. Thirty-one patients had features of the metabolic syndrome (MS) as their only risk factor. And sixteen patients had no identifiable risk factors.
“Most hepatocellular carcinoma associated with features of metabolic syndrome as the only risk factor for chronic liver disease develop in non-fibrotic liver,” the authors report. They found that just over 35 percent of liver tumors in these patients occurred in bridging fibrosis or cirrhosis, compared to 75 percent in the patients with chronic liver disease.
“Our results suggest that well-recognized multistep progression, i.e. fibrosis-cirrhosis-HCC, may not be the main carcinogenic pathway in the context of metabolic syndrome,” they write. They suggest that the metabolic syndrome itself could have a direct cancer-causing effect, perhaps through the effects of insulin, lipid peroxidation or free radical oxidative stress.
They noted that most tumors arising in the context of the metabolic syndrome were well differentiated – nearly 65 percent compared to 28 percent in the patients with chronic liver disease. These tumors were more similar to those in patients with tumors from unknown causes, which also had better differentiation and a low prevalence of significant fibrosis.
Interestingly, the researchers found that among the patients with metabolic syndrome, five cases of liver cancer were associated with liver cell adenoma (a benign liver tumor).
“Our results suggest that a significant percentage of hepatocellular carcinoma that developed in the context of metabolic syndrome without significant fibrosis arose from malignant transformation of liver cell adenoma,” they report.
Journal reference:
Paradis et al. Hepatocellular carcinomas in patients with metabolic syndrome often develop without significant liver fibrosis: A pathological analysis. Hepatology, 2009; 49 (3): 851 DOI: 10.1002/hep.22734
Adapted from materials provided by Wiley-Blackwell.
Hepatitis C: be aware
GP Dr Dylan Phillips and Shabana Begum, a hepatitis C patient determined to clear the virus, give their two individual perspectives on fighting this blood-borne infection.
Dr Dylan Phillips, GP
What's the profile of your ‘average' patient?
Hepatitis C doesn't discriminate and anyone can become infected if they're exposed to it. Since hepatitis C infection doesn't usually cause symptoms for many years, the challenge for us as healthcare professionals is to identify those at risk of infection and offer testing, as effective treatment is available.
What initially triggers you to test for hepatitis C?
We try to identify whether a patient may have ever been at risk of hepatitis C infection. We would recommend the patient be tested if they have ever: injected drugs; had a tattoo or piercing using unsterilised equipment; received medical or dental treatment abroad where unsterile equipment may have been used or received a blood transfusion before 1991 or a blood product before 1986.
How do you manage initial reaction and shock?
It's important to consider a support network for the patient at an early stage. It may be useful to direct them to local and national support services. The Hepatitis C Information Line (0800 451 451) gives patients information about hepatitis C transmission, testing, diagnosis and treatment. The Hepatitis C Trust Helpline (0845 233 4424) is staffed by people who have experience of hepatitis C and provides support for those diagnosed.
What lifestyle changes do you recommend?
Reduction or total abstinence from alcohol and advice on safe sex. Also, if the patient is overweight, we would look at ways in which we can support weight reduction.
What are the key challenges in managing the process from diagnosis to treatment?
Its vital to make sure that the patient has all the support they need to attend their appointments, whether they are at the surgery or the hospital. Patients often need help and encouragement to do so.
Has your experience in treating patients with hepatitis C altered your outlook towards testing more at risk patients?
Yes, we definitely test much more widely now as outcome of treatment is now so much better. The effective treatments for hepatitis C that are available mean that on average over half of those accessing treatment will be cured. Different strains of the virus are more responsive than others, but early diagnosis can significantly help a patient's chance of recovery.
Shabana Begum, Hep C Patient, 41
How did you become infected with hepatitis C?
I believe that I was infected with hepatitis C whilst undergoing medical treatment in Pakistan, where I lived as a young woman in the 70s.
When were you diagnosed?
I was one of the few people who actually experienced any symptoms. In 2004, I wasn't feeling very well generally. I didn't have much energy at the time and so I went to my GP who conducted a series of tests, which told me that I had hepatitis C.
What treatment did you undergo?
After a combination of pegylated interferon alpha and ribavirin for 6 months, I managed to clear the virus.
After diagnosis, how did you initially cope with the shock and stigma that surrounds hepatitis C?
I was really upset at first, I instantly thought my life was going to come to an end. Also I did experience a lot of stigma from my community, but I never hid the fact that I had the virus.
It was recommended that I go to a support group called the Peacock Project. It was really helpful for me to meet other people with hepatitis C, and to meet other people who were undergoing treatment.
How vital was the relationship between yourself and your GP in helping you come to terms with the diagnosis and treatment?
My GP was very supportive through diagnosis and he helped me deal with the side effects of the treatment. He always made time to sit down and chat with me, which was a real help through the tough times.
What message would you like to send to GPs about the importance of raising awareness of hepatitis C?
Be open-minded about who you test. Being aware of hepatitis C can save your patient's life. Also, being diagnosed with hepatitis C and undergoing treatment can be really tough so GPs need to realise how important it is to offer support.
Dr Dylan Phillips, GP
What's the profile of your ‘average' patient?
Hepatitis C doesn't discriminate and anyone can become infected if they're exposed to it. Since hepatitis C infection doesn't usually cause symptoms for many years, the challenge for us as healthcare professionals is to identify those at risk of infection and offer testing, as effective treatment is available.
What initially triggers you to test for hepatitis C?
We try to identify whether a patient may have ever been at risk of hepatitis C infection. We would recommend the patient be tested if they have ever: injected drugs; had a tattoo or piercing using unsterilised equipment; received medical or dental treatment abroad where unsterile equipment may have been used or received a blood transfusion before 1991 or a blood product before 1986.
How do you manage initial reaction and shock?
It's important to consider a support network for the patient at an early stage. It may be useful to direct them to local and national support services. The Hepatitis C Information Line (0800 451 451) gives patients information about hepatitis C transmission, testing, diagnosis and treatment. The Hepatitis C Trust Helpline (0845 233 4424) is staffed by people who have experience of hepatitis C and provides support for those diagnosed.
What lifestyle changes do you recommend?
Reduction or total abstinence from alcohol and advice on safe sex. Also, if the patient is overweight, we would look at ways in which we can support weight reduction.
What are the key challenges in managing the process from diagnosis to treatment?
Its vital to make sure that the patient has all the support they need to attend their appointments, whether they are at the surgery or the hospital. Patients often need help and encouragement to do so.
Has your experience in treating patients with hepatitis C altered your outlook towards testing more at risk patients?
Yes, we definitely test much more widely now as outcome of treatment is now so much better. The effective treatments for hepatitis C that are available mean that on average over half of those accessing treatment will be cured. Different strains of the virus are more responsive than others, but early diagnosis can significantly help a patient's chance of recovery.
Shabana Begum, Hep C Patient, 41
How did you become infected with hepatitis C?
I believe that I was infected with hepatitis C whilst undergoing medical treatment in Pakistan, where I lived as a young woman in the 70s.
When were you diagnosed?
I was one of the few people who actually experienced any symptoms. In 2004, I wasn't feeling very well generally. I didn't have much energy at the time and so I went to my GP who conducted a series of tests, which told me that I had hepatitis C.
What treatment did you undergo?
After a combination of pegylated interferon alpha and ribavirin for 6 months, I managed to clear the virus.
After diagnosis, how did you initially cope with the shock and stigma that surrounds hepatitis C?
I was really upset at first, I instantly thought my life was going to come to an end. Also I did experience a lot of stigma from my community, but I never hid the fact that I had the virus.
It was recommended that I go to a support group called the Peacock Project. It was really helpful for me to meet other people with hepatitis C, and to meet other people who were undergoing treatment.
How vital was the relationship between yourself and your GP in helping you come to terms with the diagnosis and treatment?
My GP was very supportive through diagnosis and he helped me deal with the side effects of the treatment. He always made time to sit down and chat with me, which was a real help through the tough times.
What message would you like to send to GPs about the importance of raising awareness of hepatitis C?
Be open-minded about who you test. Being aware of hepatitis C can save your patient's life. Also, being diagnosed with hepatitis C and undergoing treatment can be really tough so GPs need to realise how important it is to offer support.
BRIEF: $250,000 Approved for Officer's Liver Transplant Treatment
Feb. 23--RICHMOND -- A Smithfield policeman who contracted Hepatitis C in a 1988 attempt to save an infant's life was awarded $250,000 by the General Assembly on Monday
Beach, 52, has developed grave liver problems and is on a national waiting list for a transplant, for which his health insurance would pay.
The state money would pay for 10-years worth of organ anti-rejection drugs.
HB2243 passed with unanimous votes in the House and Senate.
Beach, 52, has developed grave liver problems and is on a national waiting list for a transplant, for which his health insurance would pay.
The state money would pay for 10-years worth of organ anti-rejection drugs.
HB2243 passed with unanimous votes in the House and Senate.
Newspaper With a Heart: Liver Disease Raised Need for Assistance
LAKE ALFRED | By the time DeWayne Oaks was diagnosed with hepatitis C, his liver was shot. That's the insidious nature of the infection. Destruction can go unnoticed for decades, until it's too late.
Confronted with the frightful diagnosis in 2006, Oaks, a trucker from Lake Alfred, sought medical treatment through the Veterans Administration. He spent the next few years in declining health and it cost him his job.
Despite monetary assistance from friends and relatives, Oaks and his wife, Barbara, who stocks shelves at Wal-Mart, find themselves unable to meet expenses, prompting a request for help through The Ledger's Newspaper with a Heart program.
Now in its 40th year, the Heart program gives families and individuals in crisis the assistance to weather a short-term financial storm. The stories reflected in the newspaper represent only a fraction of those who receive help made possible by contributions from generous donors.
Oaks, 55, finally got a new liver just a few days after Christmas, but by then he and his wife were deep in debt and facing foreclosure on their home. To buy time, relatives and friends raised nearly $8,000, said Oaks, but it wasn't enough.
With the Heart program's further assistance with household expenses, Oaks said he can make it through the next few months of recuperation from his liver transplant, then go back to work for R&L Carriers.
"I was making good money, $800 to $900 a week," Oaks said of his freight delivery days, driving an 18-wheeler on daily runs to the Cocoa Beach area, leaving at 7 a.m. and returning by 7 p.m. "I was pretty big," he said. "I could handle my own, I got my gym workout at work. But now it's hard for me to lift anything."
TRACED TO VIETNAM
Oaks traces his illness to his days as a tractor driver aboard the aircraft carrier USS Enterprise, helping launch and land aircraft from the waters off Vietnam between 1971 and 1973, when he left the Navy.
Oaks said he's not sure how he contracted hepatitis C, a virus that attacks the liver, but Vietnam veterans do have a higher than normal incidence of the disease, according to the Hepatitis Research Foundation.
Exposure to tainted blood either through direct contact or by way of infected needles is a contributing factor.
Another sobering statistic: As many as 10,000 Americans die each year from the disease, while another 1,000 are saved annually through liver transplants. Roughly two-thirds of those infected never experience early symptoms such as fatigue, muscle aches and nausea.
In Oaks' case, it began with a sharp pain in his side, which turned out to be a symptom of cirrhosis, which led to the discovery of hepatitis C. For two years the VA doctors kept Oaks somewhat stable through medications, he said, but his condition and the pain worsened.
Too weak and disoriented to continue driving for a living, Oaks took advantage of the Family Medical Leave Act and stopped working in September. He said he was counseled to drop medical coverage through the VA so that he might increase his chances for a liver transplant.
"They told me it was because of all the red tape and bureaucracy in Washington" that veterans who use the VA wait longer for a transplant, Oaks said.
So in October, using his employer-based health policy, Oaks was able to obtain the services of LifeLink Foundation and Tampa General Hospital. There was more testing, medications and a diet of mostly leafy greens, chicken and fish.
And then on Dec. 27 at 3:30 a.m. he got the first phone call from LifeLink.
The Oaks jumped in their car and drove to the Tampa hospital, only to learn a few hours later that the donor kidney did not pass the scrutiny of his doctors. The Oaks were sent home.
"It didn't bother me too much," Oaks said. "I wasn't really ready, I was so nervous. You don't realize the emotions you go through. When they said go home I could kind of calm down."
He and his wife said that hospital staff raised hopes for a second chance by mentioning that the traffic death rate rises during the holidays, because more people are drinking and driving. And while they're not certain of the circumstances, the Oaks were back at TGH the next evening. By 8 p.m. Oaks was under the knife.
"That liver transplant just changed my life," he said. "The pain is gone."
Confronted with the frightful diagnosis in 2006, Oaks, a trucker from Lake Alfred, sought medical treatment through the Veterans Administration. He spent the next few years in declining health and it cost him his job.
Despite monetary assistance from friends and relatives, Oaks and his wife, Barbara, who stocks shelves at Wal-Mart, find themselves unable to meet expenses, prompting a request for help through The Ledger's Newspaper with a Heart program.
Now in its 40th year, the Heart program gives families and individuals in crisis the assistance to weather a short-term financial storm. The stories reflected in the newspaper represent only a fraction of those who receive help made possible by contributions from generous donors.
Oaks, 55, finally got a new liver just a few days after Christmas, but by then he and his wife were deep in debt and facing foreclosure on their home. To buy time, relatives and friends raised nearly $8,000, said Oaks, but it wasn't enough.
With the Heart program's further assistance with household expenses, Oaks said he can make it through the next few months of recuperation from his liver transplant, then go back to work for R&L Carriers.
"I was making good money, $800 to $900 a week," Oaks said of his freight delivery days, driving an 18-wheeler on daily runs to the Cocoa Beach area, leaving at 7 a.m. and returning by 7 p.m. "I was pretty big," he said. "I could handle my own, I got my gym workout at work. But now it's hard for me to lift anything."
TRACED TO VIETNAM
Oaks traces his illness to his days as a tractor driver aboard the aircraft carrier USS Enterprise, helping launch and land aircraft from the waters off Vietnam between 1971 and 1973, when he left the Navy.
Oaks said he's not sure how he contracted hepatitis C, a virus that attacks the liver, but Vietnam veterans do have a higher than normal incidence of the disease, according to the Hepatitis Research Foundation.
Exposure to tainted blood either through direct contact or by way of infected needles is a contributing factor.
Another sobering statistic: As many as 10,000 Americans die each year from the disease, while another 1,000 are saved annually through liver transplants. Roughly two-thirds of those infected never experience early symptoms such as fatigue, muscle aches and nausea.
In Oaks' case, it began with a sharp pain in his side, which turned out to be a symptom of cirrhosis, which led to the discovery of hepatitis C. For two years the VA doctors kept Oaks somewhat stable through medications, he said, but his condition and the pain worsened.
Too weak and disoriented to continue driving for a living, Oaks took advantage of the Family Medical Leave Act and stopped working in September. He said he was counseled to drop medical coverage through the VA so that he might increase his chances for a liver transplant.
"They told me it was because of all the red tape and bureaucracy in Washington" that veterans who use the VA wait longer for a transplant, Oaks said.
So in October, using his employer-based health policy, Oaks was able to obtain the services of LifeLink Foundation and Tampa General Hospital. There was more testing, medications and a diet of mostly leafy greens, chicken and fish.
And then on Dec. 27 at 3:30 a.m. he got the first phone call from LifeLink.
The Oaks jumped in their car and drove to the Tampa hospital, only to learn a few hours later that the donor kidney did not pass the scrutiny of his doctors. The Oaks were sent home.
"It didn't bother me too much," Oaks said. "I wasn't really ready, I was so nervous. You don't realize the emotions you go through. When they said go home I could kind of calm down."
He and his wife said that hospital staff raised hopes for a second chance by mentioning that the traffic death rate rises during the holidays, because more people are drinking and driving. And while they're not certain of the circumstances, the Oaks were back at TGH the next evening. By 8 p.m. Oaks was under the knife.
"That liver transplant just changed my life," he said. "The pain is gone."
Health District Wants Power to Protect Patients
When more than 100 cases of hepatitis C were linked to two Las Vegas medical centers last year, it became the largest outbreak of the disease in the United States. Nevada lawmakers want to give health officials more legal muscle when it comes to dealing with these kinds of situations.
The outbreak involved the Endoscopy Center of Southern Nevada on Shadow Lane and the Desert Shadow Endoscopy Center on Burnham Avenue which potentially exposed nearly 60,000 people to the blood-borne illness by reusing syringes and failing to properly clean medical equipment between procedures.
(Dr. Dipak Desai who is accused of using the unsafe practices has been ordered to have an independent medical evaluation)
The Southern Nevada Health District uncovered the unsafe practices but did not have the authority to close the clinics. Lawmakers, who will meet on Saturday for a public hearing, want to change that. They are reviewing three proposed bills. Among other things, the bills would give the health district the authority to close a medical business if there is a potential danger to patients. Ultimately, in the hepatitis C case, it was the city that pulled the business licenses of the medical clinics and that took weeks.
In addition, when it came to fines, the State Bureau of Licensure could only fine the center a maximum of a few thousand dollars for putting all of those patients at risk. The new bills would give local health districts more teeth in levying fines and making doctors pay for the investigation or any patient treatment.
"We need to make changes so that we can prevent this kind of event from happening again as well as improve our ability to take action when we discover that," said Lawrence Sands, SNHD Chief Medical Officer.
The all day public hearing takes place at the Grant Sawyer building.
The outbreak involved the Endoscopy Center of Southern Nevada on Shadow Lane and the Desert Shadow Endoscopy Center on Burnham Avenue which potentially exposed nearly 60,000 people to the blood-borne illness by reusing syringes and failing to properly clean medical equipment between procedures.
(Dr. Dipak Desai who is accused of using the unsafe practices has been ordered to have an independent medical evaluation)
The Southern Nevada Health District uncovered the unsafe practices but did not have the authority to close the clinics. Lawmakers, who will meet on Saturday for a public hearing, want to change that. They are reviewing three proposed bills. Among other things, the bills would give the health district the authority to close a medical business if there is a potential danger to patients. Ultimately, in the hepatitis C case, it was the city that pulled the business licenses of the medical clinics and that took weeks.
In addition, when it came to fines, the State Bureau of Licensure could only fine the center a maximum of a few thousand dollars for putting all of those patients at risk. The new bills would give local health districts more teeth in levying fines and making doctors pay for the investigation or any patient treatment.
"We need to make changes so that we can prevent this kind of event from happening again as well as improve our ability to take action when we discover that," said Lawrence Sands, SNHD Chief Medical Officer.
The all day public hearing takes place at the Grant Sawyer building.
Haemophilia patients infected with Hepatitis C and HIV 'should be compensated'
Haemophilia patients infected with Hepatitis C and HIV through infected blood should receive compensation, an inquiry will say.
Thousands of patients with the bleeding disorder haemophilia have been exposed to successive viruses through treatment with clotting products made from donor blood and 1,757 have since died.
An independent inquiry, chaired by former solicitor general Lord Archer of Sandwell, is due to report on Monday into the contamination of blood and products made using blood.
In the 1970s and 1980s blood derivatives were sourced from within the UK and from the USA where donors were paid and often funded their drug habit through the payments. Blood was later found to be infected with Hepatitis C and later HIV and thousands became infected through using the products.
Successive governments have failed to acknowledge any fault and compensation has so far been limited to 'ex gratia payments', Lord Archer of Sandwell said at the opening of the inquiry in March 2007.
The inquiry is expected to recommend that further compensation payments be made to those who have contracted viruses and the families of those who have since died.
The report will also point to the new danger to haemophiliacs of vCJD as they may have been given products contaminated with the human form of mad cow disease before the 1998 ruling that all clotting factors should be sourced from outside the UK.
Earlier this week the Health Protection Agency confirmed the death of the first haemophiliac to have contracted vCJD from contaminated blood although this did not cause his death. The donor died six months after giving blood in 1996.
All patients with bleeding conditions were told in 2004 that they were at risk of having contracted vCJD from contaminated products that were administered between 1980 and 2001.
The inquiry was set up by Lord Morris of Manchester, who is president of the Haemophilia Society, who has fought for better treatment of patients infected with contaminated blood products for a number of years.
Former health minister Dr Lord Owen has given evidence along with patients, doctors and advocates.
In 1998 the Department of Health announced that plasma for clotting factors would be sourced from outside the UK and synthetic products were introduced for all patients in Scotland and Wales, but these were restricted to children under 16 only in England.
One of the patients who contracted hepatitis C through infected products, campaigner Peter Mossman, said: "I hope the inquiry will draw a line under this. We are all tired and what it over with."
The patients gave evidence that they have faced financial hardship since becoming infected with many becoming too ill to work and they have argued they cannot get health insurance because of their condition.
Thousands of patients with the bleeding disorder haemophilia have been exposed to successive viruses through treatment with clotting products made from donor blood and 1,757 have since died.
An independent inquiry, chaired by former solicitor general Lord Archer of Sandwell, is due to report on Monday into the contamination of blood and products made using blood.
In the 1970s and 1980s blood derivatives were sourced from within the UK and from the USA where donors were paid and often funded their drug habit through the payments. Blood was later found to be infected with Hepatitis C and later HIV and thousands became infected through using the products.
Successive governments have failed to acknowledge any fault and compensation has so far been limited to 'ex gratia payments', Lord Archer of Sandwell said at the opening of the inquiry in March 2007.
The inquiry is expected to recommend that further compensation payments be made to those who have contracted viruses and the families of those who have since died.
The report will also point to the new danger to haemophiliacs of vCJD as they may have been given products contaminated with the human form of mad cow disease before the 1998 ruling that all clotting factors should be sourced from outside the UK.
Earlier this week the Health Protection Agency confirmed the death of the first haemophiliac to have contracted vCJD from contaminated blood although this did not cause his death. The donor died six months after giving blood in 1996.
All patients with bleeding conditions were told in 2004 that they were at risk of having contracted vCJD from contaminated products that were administered between 1980 and 2001.
The inquiry was set up by Lord Morris of Manchester, who is president of the Haemophilia Society, who has fought for better treatment of patients infected with contaminated blood products for a number of years.
Former health minister Dr Lord Owen has given evidence along with patients, doctors and advocates.
In 1998 the Department of Health announced that plasma for clotting factors would be sourced from outside the UK and synthetic products were introduced for all patients in Scotland and Wales, but these were restricted to children under 16 only in England.
One of the patients who contracted hepatitis C through infected products, campaigner Peter Mossman, said: "I hope the inquiry will draw a line under this. We are all tired and what it over with."
The patients gave evidence that they have faced financial hardship since becoming infected with many becoming too ill to work and they have argued they cannot get health insurance because of their condition.
Results may determine fate of Human Genome Sciences
Vandana Sinha Staff Reporter
Washington Business Journal
Fruition or failure: The test results on a hepatis drug could be the fruition of years of hard work or lead to the demise of Tom Watkins’ company.
Sometime this month, Rockville’s Human Genome Sciences Inc. will receive conclusive results from arguably its most crucial clinical trials of a hepatitis C drug, what analysts consider the 16-year-old company’s best shot at breaking into the commercial market.
Positive data would boost HGSI’s plan to apply by fall for federal approval to begin selling the drug, its first ever for pharmacy shelves.
But market insiders agree that a clinical trial failure would be disastrous for the 880-person company, which has piled up a $2 billion debt over its lifetime and, more dauntingly, has more than $400 million in debt coming due by 2012.
“Our view is that the trial should meet its primary endpoint,” said Edward Tenthoff, managing director of Piper Jaffray and Co., a research organization. But if the trial fails, which is a “long shot,” Tenthoff said, “the company would be in very serious trouble. The stock would be under severe pressure. At this point, the debt level is higher than the cash. We would see the stock basically fold.”
This is a test of nerves for HGSI at a time when, ironically, the company is basking in its biggest success so far. HGSI shipped its first product last month, an anthrax treatment called ABThrax to the Department of Health and Human Services, and is expecting $150 million in its first sales revenue from the contract this year.
“This is likely to be the year a lot of the painstaking work over many, many years comes to positive fruition for our company and our shareholders,” said HGSI’s chief executive officer, Tom Watkins, in a recent interview. “You know that the people around you are doing things right. While everything may not work out, you know you’re doing everything you can. And this company is doing everything it can to serve patients and get these opportunities out. Are we anxious? Sure. But we’re more excited.”
In this final stage of studies, HGSI need only prove that its hepatitis C drug, Albuferon, which is given every two weeks, works as effectively as its competitors’ drugs, which are all weekly doses.
While analysts see room for HGSI in an estimated $2.4 billion hepatitis C market, the field is still dominated by Roche and Schering-Plough Corp., pharmaceutical heavyweights that make HGSI look skeletal in comparison. HGSI also will have to study Albuferon’s compatibility with emerging antibiotics expected to revolutionize the hepatitis C drug market.
For now, the company argues it is halfway there, having reached its goal of showing Albuferon’s overall effectiveness in similar clinical trials late last year on two different, albeit easier-to-treat, strains of the debilitating disease.
However, HGSI has not escaped skepticism. After receiving reports last year of pulmonary problems with Albuferon, the company had to significantly lower the doses for clinical-trial patients in a high-profile setback that, in one day, chopped its stock price nearly in half. HGSI has been unable to return to its $10 levels since.
While some observers worried a lower dose would make Albuferon a weaker challenger to its rival drugs, others say they are closely watching the potential for harmful side effects in the upcoming trial data.
Despite HGSI’s enthusiastic lineup of existing late-stage products, most analysts still see Albuferon as the headliner. ABThrax is geared primarily to the government, and two drugs are licensed to other pharmaceutical companies, which are developing them.
HGSI’s other key drug candidate, a lupus treatment called LymphoStat-B, is undergoing advanced clinical trials whose results are due in July and November. But it does not inspire much confidence on Wall Street.
“Most people do not expect the lupus drug to work,” said Liisa Bayko, director and senior analyst with JMP Securities LLC, who believes Albuferon will get a passing grade but describes lupus as an inordinately difficult disease to treat.
“It’s a very high-risk program, frankly,” she said.
That only ups the ante for the Albuferon trials in a recession-weary investor community that dragged HGSI’s stock down below $2 by the first week of March.
“If this doesn’t work, you’ve got a company with two failed Phase 3 programs, and they’ve dumped a lot of money in it,” Bayko said. “It becomes a solvency issue.”
Washington Business Journal
Fruition or failure: The test results on a hepatis drug could be the fruition of years of hard work or lead to the demise of Tom Watkins’ company.
Sometime this month, Rockville’s Human Genome Sciences Inc. will receive conclusive results from arguably its most crucial clinical trials of a hepatitis C drug, what analysts consider the 16-year-old company’s best shot at breaking into the commercial market.
Positive data would boost HGSI’s plan to apply by fall for federal approval to begin selling the drug, its first ever for pharmacy shelves.
But market insiders agree that a clinical trial failure would be disastrous for the 880-person company, which has piled up a $2 billion debt over its lifetime and, more dauntingly, has more than $400 million in debt coming due by 2012.
“Our view is that the trial should meet its primary endpoint,” said Edward Tenthoff, managing director of Piper Jaffray and Co., a research organization. But if the trial fails, which is a “long shot,” Tenthoff said, “the company would be in very serious trouble. The stock would be under severe pressure. At this point, the debt level is higher than the cash. We would see the stock basically fold.”
This is a test of nerves for HGSI at a time when, ironically, the company is basking in its biggest success so far. HGSI shipped its first product last month, an anthrax treatment called ABThrax to the Department of Health and Human Services, and is expecting $150 million in its first sales revenue from the contract this year.
“This is likely to be the year a lot of the painstaking work over many, many years comes to positive fruition for our company and our shareholders,” said HGSI’s chief executive officer, Tom Watkins, in a recent interview. “You know that the people around you are doing things right. While everything may not work out, you know you’re doing everything you can. And this company is doing everything it can to serve patients and get these opportunities out. Are we anxious? Sure. But we’re more excited.”
In this final stage of studies, HGSI need only prove that its hepatitis C drug, Albuferon, which is given every two weeks, works as effectively as its competitors’ drugs, which are all weekly doses.
While analysts see room for HGSI in an estimated $2.4 billion hepatitis C market, the field is still dominated by Roche and Schering-Plough Corp., pharmaceutical heavyweights that make HGSI look skeletal in comparison. HGSI also will have to study Albuferon’s compatibility with emerging antibiotics expected to revolutionize the hepatitis C drug market.
For now, the company argues it is halfway there, having reached its goal of showing Albuferon’s overall effectiveness in similar clinical trials late last year on two different, albeit easier-to-treat, strains of the debilitating disease.
However, HGSI has not escaped skepticism. After receiving reports last year of pulmonary problems with Albuferon, the company had to significantly lower the doses for clinical-trial patients in a high-profile setback that, in one day, chopped its stock price nearly in half. HGSI has been unable to return to its $10 levels since.
While some observers worried a lower dose would make Albuferon a weaker challenger to its rival drugs, others say they are closely watching the potential for harmful side effects in the upcoming trial data.
Despite HGSI’s enthusiastic lineup of existing late-stage products, most analysts still see Albuferon as the headliner. ABThrax is geared primarily to the government, and two drugs are licensed to other pharmaceutical companies, which are developing them.
HGSI’s other key drug candidate, a lupus treatment called LymphoStat-B, is undergoing advanced clinical trials whose results are due in July and November. But it does not inspire much confidence on Wall Street.
“Most people do not expect the lupus drug to work,” said Liisa Bayko, director and senior analyst with JMP Securities LLC, who believes Albuferon will get a passing grade but describes lupus as an inordinately difficult disease to treat.
“It’s a very high-risk program, frankly,” she said.
That only ups the ante for the Albuferon trials in a recession-weary investor community that dragged HGSI’s stock down below $2 by the first week of March.
“If this doesn’t work, you’ve got a company with two failed Phase 3 programs, and they’ve dumped a lot of money in it,” Bayko said. “It becomes a solvency issue.”
NYC dialysis center tied to 9 hepatitis C cases
By KAREN MATTHEWS Associated Press Writer
NEW YORK—A New York City kidney dialysis center remains closed after state health inspectors found that nine patients contracted hepatitis C there over a seven-year period, according to a report released Thursday.
The Life Care Dialysis Center in Manhattan shut its doors in September after the inspectors found unsanitary conditions including blood on chairs and machines, the federal Centers for Disease Control and Prevention said in its summary of the investigation results.
Hepatitis C is a liver disease caused by a virus and spread by contact with the blood of an infected person.
According to the report in the CDC's Morbidity and Mortality Weekly Report, Life Care Dialysis Center staff members failed to change gloves between patients or to clean and disinfect equipment properly.
Once the patients tested positive for hepatitis C, the clinic failed to inform the patients or to notify the city Health Department, the CDC said.
After the first case was discovered, letters went out to more than 600 patients who had received dialysis there urging them to get tested.
The for-profit dialysis center was operated by DaVita Inc., an El Segundo, Calif.-based company that runs more than 1,400 outpatient dialysis centers. A message left at the company Thursday was not immediately returned.
NEW YORK—A New York City kidney dialysis center remains closed after state health inspectors found that nine patients contracted hepatitis C there over a seven-year period, according to a report released Thursday.
The Life Care Dialysis Center in Manhattan shut its doors in September after the inspectors found unsanitary conditions including blood on chairs and machines, the federal Centers for Disease Control and Prevention said in its summary of the investigation results.
Hepatitis C is a liver disease caused by a virus and spread by contact with the blood of an infected person.
According to the report in the CDC's Morbidity and Mortality Weekly Report, Life Care Dialysis Center staff members failed to change gloves between patients or to clean and disinfect equipment properly.
Once the patients tested positive for hepatitis C, the clinic failed to inform the patients or to notify the city Health Department, the CDC said.
After the first case was discovered, letters went out to more than 600 patients who had received dialysis there urging them to get tested.
The for-profit dialysis center was operated by DaVita Inc., an El Segundo, Calif.-based company that runs more than 1,400 outpatient dialysis centers. A message left at the company Thursday was not immediately returned.
Proteomics Prove Accurate In Identifying Liver Cancer
As the incidence of liver cancer continues to grow-- fueled in large part, by rising rates of hepatitis C infections – so too does the need for tests to help diagnose the disease at an earlier stage.
A study appearing in the January 15, 2008, issue of Clinical Cancer Research demonstrates that a novel mass-spectrometry based form of proteomic profiling is more accurate than traditional biomarkers in distinguishing liver cancer patients from patients with hepatitis C liver cirrhosis, particularly with regard to identifying patients with small, curable tumors. Led by researchers at Beth Israel Deaconess Medical Center (BIDMC), the study could help lead to earlier diagnostic methods – and subsequent treatments -- for liver cancer.
“Proteomics represents a potentially powerful tool for the serologic recognition of protein profiles associated with cancer,” explains co-senior author Towia Libermann, PhD, Director of the Genomics Center at BIDMC and Associate Professor of Medicine at Harvard Medical School. “Although this particular proteomics technology, SELDI-TOF MS [surface enhanced laser desorption/ionization time of flight mass spectrometry] had already proven capable of identifying liver cancer in some limited studies, this was the first time that the technology was compared side-by-side with the clinical standard biomarker in a cohort of patients at risk for developing the disease,” adds Liebermann, who is also Director of the Dana-Farber/Harvard Cancer Center Proteomics Core in the Division of Interdisciplinary Medicine and Biotechnology at BIDMC.
Over a single decade, the incidence of liver cancer (hepatocellular carcinoma) increased from 1.8 to 2.5 per 100,000 patients, in large part due to a rise in the spread of hepatitis C virus.
“Hepatitis C has become a tremendous public health problem,” explains co-senior author Nezam Afdhal, MD, Director of the Liver Center at BIDMC and Associate Professor of Medicine at Harvard Medical School. “And a significant number of hepatitis C-infected patients will go on to develop liver cirrhosis.”
Cirrhosis results when healthy tissue is replaced by scar tissue, preventing the liver from properly functioning. Cirrhosis itself is responsible for more than 25,000 deaths each year. But, adds Afdhal, secondarily, cirrhosis greatly increases a person’s chances of developing liver cancer.
“Each year, cirrhosis patients have a two to five percent chance that their condition will escalate to cancer,” he explains. “And the problem is that, right now, there is no reliable means of detecting liver cancer at an early stage, when surgical treatment is an option. Typically by the time the disease is discovered, the cancer has advanced and treatment options become much more limited.”
The best hope for early detection is cancer biomarkers, serum proteins found in altered amounts in blood or other body fluids. The current biomarker for liver cancer in clinical use is alpha fetoprotein (AFP). In many cases, patients with hepatitis C undergo routine monitoring for AFP levels as an indicator of whether tumors may have developed in their livers.
But, as Libermann explains, the AFP biomarker has a number of shortcomings, including false positives and false negatives. “AFP not only fails to detect many early tumors, but it also lacks specificity. Consequently, elevated AFP levels could be indicators of not only cancer, but also of other liver diseases or even benign conditions, while on the other hand, many patients with small tumors will test negative for AFP.”
The authors, therefore, decided to evaluate the sensitivity and specificity of SELDI-TOF MS for the detection of liver cancer and to compare its effectiveness with AFP.
Examining serum samples of 92 patients – including 51 patients with liver cirrhosis and 41 patients with liver cancer, and among the cancer patients, individuals with both large and small (less than 2 cm) tumors -- by SELDI-TOF mass spectrometry, the investigators were able to identify an 11-protein signature that accurately discriminated between the cirrhosis and cancer patients, first in a training set (made up of 26 cirrhosis and 20 liver cancer patients), and then again in an independent validation set (consisting of 25 cirrhosis and 19 liver cancer patients). The resulting diagnostic value – 74 percent sensitivity and 88 percent specificity – compared favorably with the diagnostic accuracy of AFP (73 percent sensitivity and 71 percent specificity) as well as with two other biomarkers currently in clinical development for liver cancer, AFP-L3 and PIVKA-IL.
“Most strikingly,” notes Libermann, “in patients with small tumors (less than 2 cm), where AFP identified only three, and AFP-L3 and PIVKA-II only one each, the 11-protein signature correctly identified seven of eight patients at this early stage of disease.
“Biomarkers play a major role in all aspects of personalized medicine, not only in early disease detection, but also in outcome prediction and evaluation of therapeutic responses,” he adds. “This study provides strong evidence that serum contains early detection biomarkers and supports the notion that a combination of multiple biomarkers may prove more effective than individual biomarkers for diagnosis of liver cancer, as well as other cancers.”
This study was funded by grants from the National Institutes of Health.
A study appearing in the January 15, 2008, issue of Clinical Cancer Research demonstrates that a novel mass-spectrometry based form of proteomic profiling is more accurate than traditional biomarkers in distinguishing liver cancer patients from patients with hepatitis C liver cirrhosis, particularly with regard to identifying patients with small, curable tumors. Led by researchers at Beth Israel Deaconess Medical Center (BIDMC), the study could help lead to earlier diagnostic methods – and subsequent treatments -- for liver cancer.
“Proteomics represents a potentially powerful tool for the serologic recognition of protein profiles associated with cancer,” explains co-senior author Towia Libermann, PhD, Director of the Genomics Center at BIDMC and Associate Professor of Medicine at Harvard Medical School. “Although this particular proteomics technology, SELDI-TOF MS [surface enhanced laser desorption/ionization time of flight mass spectrometry] had already proven capable of identifying liver cancer in some limited studies, this was the first time that the technology was compared side-by-side with the clinical standard biomarker in a cohort of patients at risk for developing the disease,” adds Liebermann, who is also Director of the Dana-Farber/Harvard Cancer Center Proteomics Core in the Division of Interdisciplinary Medicine and Biotechnology at BIDMC.
Over a single decade, the incidence of liver cancer (hepatocellular carcinoma) increased from 1.8 to 2.5 per 100,000 patients, in large part due to a rise in the spread of hepatitis C virus.
“Hepatitis C has become a tremendous public health problem,” explains co-senior author Nezam Afdhal, MD, Director of the Liver Center at BIDMC and Associate Professor of Medicine at Harvard Medical School. “And a significant number of hepatitis C-infected patients will go on to develop liver cirrhosis.”
Cirrhosis results when healthy tissue is replaced by scar tissue, preventing the liver from properly functioning. Cirrhosis itself is responsible for more than 25,000 deaths each year. But, adds Afdhal, secondarily, cirrhosis greatly increases a person’s chances of developing liver cancer.
“Each year, cirrhosis patients have a two to five percent chance that their condition will escalate to cancer,” he explains. “And the problem is that, right now, there is no reliable means of detecting liver cancer at an early stage, when surgical treatment is an option. Typically by the time the disease is discovered, the cancer has advanced and treatment options become much more limited.”
The best hope for early detection is cancer biomarkers, serum proteins found in altered amounts in blood or other body fluids. The current biomarker for liver cancer in clinical use is alpha fetoprotein (AFP). In many cases, patients with hepatitis C undergo routine monitoring for AFP levels as an indicator of whether tumors may have developed in their livers.
But, as Libermann explains, the AFP biomarker has a number of shortcomings, including false positives and false negatives. “AFP not only fails to detect many early tumors, but it also lacks specificity. Consequently, elevated AFP levels could be indicators of not only cancer, but also of other liver diseases or even benign conditions, while on the other hand, many patients with small tumors will test negative for AFP.”
The authors, therefore, decided to evaluate the sensitivity and specificity of SELDI-TOF MS for the detection of liver cancer and to compare its effectiveness with AFP.
Examining serum samples of 92 patients – including 51 patients with liver cirrhosis and 41 patients with liver cancer, and among the cancer patients, individuals with both large and small (less than 2 cm) tumors -- by SELDI-TOF mass spectrometry, the investigators were able to identify an 11-protein signature that accurately discriminated between the cirrhosis and cancer patients, first in a training set (made up of 26 cirrhosis and 20 liver cancer patients), and then again in an independent validation set (consisting of 25 cirrhosis and 19 liver cancer patients). The resulting diagnostic value – 74 percent sensitivity and 88 percent specificity – compared favorably with the diagnostic accuracy of AFP (73 percent sensitivity and 71 percent specificity) as well as with two other biomarkers currently in clinical development for liver cancer, AFP-L3 and PIVKA-IL.
“Most strikingly,” notes Libermann, “in patients with small tumors (less than 2 cm), where AFP identified only three, and AFP-L3 and PIVKA-II only one each, the 11-protein signature correctly identified seven of eight patients at this early stage of disease.
“Biomarkers play a major role in all aspects of personalized medicine, not only in early disease detection, but also in outcome prediction and evaluation of therapeutic responses,” he adds. “This study provides strong evidence that serum contains early detection biomarkers and supports the notion that a combination of multiple biomarkers may prove more effective than individual biomarkers for diagnosis of liver cancer, as well as other cancers.”
This study was funded by grants from the National Institutes of Health.
Continuous antiretroviral therapy improves survival in HIV/hepatitis C co-infected patients with liver cirrhosis
Antiretroviral therapy - but not treatment for chronic hepatitis C virus (HCV) infection - was associated with significantly improved survival in HIV/HCV co-infected individuals with liver cirrhosis, researchers reported on February 10th at the Sixteenth Conference on Retroviruses and Opportunistic Infections (CROI) in Montreal, Canada.
Maria Luisa Montes from Hospital Universitario La Paz in Madrid, Spain, presented findings from a prospective multicentre study looking at the effect of hepatitis C treatment in HIV/HCV co-infected patients with compensated cirrhosis or advanced fibrosis.
Compensated cirrhosis means that even though the liver has been heavily scarred, it is still able to perform most of its normal functions. Chronic hepatitis C is responsible for more than 90% of cirrhosis cases in HIV-positive people, the researchers noted.
A total of 248 co-infected participants were assessed to determine factors associated with survival and time to a first episode of liver decompensation, and in particular whether hepatitis C treatment improved the prognosis of patients with compensated cirrhosis.
The investigators used an expanded definition of survival that included development of liver cancer and liver transplantation in addition to death.
Liver decompensation included bleeding in the oesophagus or stomach, abdominal fluid accumulation (ascites), brain damage (encephalopathy), spontaneous bacterial infection of the abdominal lining (peritonitis) and kidney failure (hepatorenal syndrome).
The factors the investigators included in their analysis were current and nadir (lowest-ever) CD4 cell count, HIV viral load, type of antiretroviral therapy, HCV genotype, whether patients had received hepatitis C treatment and whether they achieved sustained virological response (continued undetectable HCV viral load 24 weeks after completing treatment), concurrent chronic hepatitis B, and Child-Pugh score (a measure of liver disease prognosis).
More than three-quarters (78%) of the study participants were men and the median age was 42 years. Most had a history of injecting drug use. Overall, they had well-controlled HIV disease, with 88% taking combination antiretroviral therapy at baseline, 60% receiving continuous antiretroviral treatment without interruptions for the duration of the study, and 60% with undetectable HIV viral load; the median CD4 cell count was 437 cells/mm3.
With regard to liver disease, participants had been infected with HCV for 23 years on average and had cirrhosis or advanced bridging fibrosis, diagnosed for one year on average. About three-quarters had the harder to treat HCV genotypes 1 and 4. In addition, 27% were heavy alcohol drinkers and 4% also had chronic hepatitis B.
About three-quarters were currently taking or had received treatment for hepatitis C - mostly using the standard of care regimen of pegylated interferon plus ribavirin - and the sustained virological response rate was 24%, leaving 74% as relapsers or non-responders (1% were still undergoing treatment).
During a median 34 months of follow-up, a total of 30 endpoints were recorded: 25 deaths, 2 cases of liver cancer and 5 liver transplants. In addition, 28 patients experienced a first episode of liver decompensation, most often ascites.
The overall survival rate for co-infected patients with compensated cirrhosis was 85% at three years. In a univariate analysis, participants treated for hepatitis C were significantly more likely than untreated patients to survive during the follow-up period (91% vs 71% at three years), but the difference between sustained responders and non-responders was not significant (95% vs 90% at three years).
Hepatitis C treatment did not increase the time to a first episode of decompensation, nor did sustained response compared with non-response.
In a multivariate analysis controlling for potential confounding factors, only a baseline Child-Pugh score of 'B' or 'C' (indicating 81% and 45% probability of one-year survival, respectively) and non-continuous use of antiretroviral therapy were significantly associated with first liver decompensation and decreased survival, whilst decompensation during follow-up also predicted death, liver cancer or transplantation.
Although treatment of chronic hepatitis C was significantly associated with increased survival over three years in the univariate analysis, the investigators noted, this association disappeared after controlling for other factors.
“Continuous antiretroviral therapy and Child-Pugh scores are more important prognostic factors than anti-hepatitis C treatment”, they concluded.
They added the caveat that this study does not rule out a possible survival benefit of sustained response to hepatitis C treatment due to the low number of participants, and said longer follow-up might be needed to see an effect.
Because the success rate of hepatitis C treatment in co-infected individuals with liver cirrhosis is low, the researchers recommended that "every effort should be made to avoid progression to cirrhosis" in HIV/HCV co-infected patients - an argument for timely HCV screening, regular monitoring of liver health and prompt treatment when indicated.
Reference
Montes ML et al. Survival of HIV/HCV-co-infected patients with compensated liver cirrhosis: effect of HCV therapy. Sixteenth Conference on Retroviruses and Opportunistic Infections, Montreal, abstract 106, 2009.
Maria Luisa Montes from Hospital Universitario La Paz in Madrid, Spain, presented findings from a prospective multicentre study looking at the effect of hepatitis C treatment in HIV/HCV co-infected patients with compensated cirrhosis or advanced fibrosis.
Compensated cirrhosis means that even though the liver has been heavily scarred, it is still able to perform most of its normal functions. Chronic hepatitis C is responsible for more than 90% of cirrhosis cases in HIV-positive people, the researchers noted.
A total of 248 co-infected participants were assessed to determine factors associated with survival and time to a first episode of liver decompensation, and in particular whether hepatitis C treatment improved the prognosis of patients with compensated cirrhosis.
The investigators used an expanded definition of survival that included development of liver cancer and liver transplantation in addition to death.
Liver decompensation included bleeding in the oesophagus or stomach, abdominal fluid accumulation (ascites), brain damage (encephalopathy), spontaneous bacterial infection of the abdominal lining (peritonitis) and kidney failure (hepatorenal syndrome).
The factors the investigators included in their analysis were current and nadir (lowest-ever) CD4 cell count, HIV viral load, type of antiretroviral therapy, HCV genotype, whether patients had received hepatitis C treatment and whether they achieved sustained virological response (continued undetectable HCV viral load 24 weeks after completing treatment), concurrent chronic hepatitis B, and Child-Pugh score (a measure of liver disease prognosis).
More than three-quarters (78%) of the study participants were men and the median age was 42 years. Most had a history of injecting drug use. Overall, they had well-controlled HIV disease, with 88% taking combination antiretroviral therapy at baseline, 60% receiving continuous antiretroviral treatment without interruptions for the duration of the study, and 60% with undetectable HIV viral load; the median CD4 cell count was 437 cells/mm3.
With regard to liver disease, participants had been infected with HCV for 23 years on average and had cirrhosis or advanced bridging fibrosis, diagnosed for one year on average. About three-quarters had the harder to treat HCV genotypes 1 and 4. In addition, 27% were heavy alcohol drinkers and 4% also had chronic hepatitis B.
About three-quarters were currently taking or had received treatment for hepatitis C - mostly using the standard of care regimen of pegylated interferon plus ribavirin - and the sustained virological response rate was 24%, leaving 74% as relapsers or non-responders (1% were still undergoing treatment).
During a median 34 months of follow-up, a total of 30 endpoints were recorded: 25 deaths, 2 cases of liver cancer and 5 liver transplants. In addition, 28 patients experienced a first episode of liver decompensation, most often ascites.
The overall survival rate for co-infected patients with compensated cirrhosis was 85% at three years. In a univariate analysis, participants treated for hepatitis C were significantly more likely than untreated patients to survive during the follow-up period (91% vs 71% at three years), but the difference between sustained responders and non-responders was not significant (95% vs 90% at three years).
Hepatitis C treatment did not increase the time to a first episode of decompensation, nor did sustained response compared with non-response.
In a multivariate analysis controlling for potential confounding factors, only a baseline Child-Pugh score of 'B' or 'C' (indicating 81% and 45% probability of one-year survival, respectively) and non-continuous use of antiretroviral therapy were significantly associated with first liver decompensation and decreased survival, whilst decompensation during follow-up also predicted death, liver cancer or transplantation.
Although treatment of chronic hepatitis C was significantly associated with increased survival over three years in the univariate analysis, the investigators noted, this association disappeared after controlling for other factors.
“Continuous antiretroviral therapy and Child-Pugh scores are more important prognostic factors than anti-hepatitis C treatment”, they concluded.
They added the caveat that this study does not rule out a possible survival benefit of sustained response to hepatitis C treatment due to the low number of participants, and said longer follow-up might be needed to see an effect.
Because the success rate of hepatitis C treatment in co-infected individuals with liver cirrhosis is low, the researchers recommended that "every effort should be made to avoid progression to cirrhosis" in HIV/HCV co-infected patients - an argument for timely HCV screening, regular monitoring of liver health and prompt treatment when indicated.
Reference
Montes ML et al. Survival of HIV/HCV-co-infected patients with compensated liver cirrhosis: effect of HCV therapy. Sixteenth Conference on Retroviruses and Opportunistic Infections, Montreal, abstract 106, 2009.
Rates of Liver Cancer are Rising, but Survival is Increasing
March 4, 2009 — The incidence of hepatocellular carcinoma (HCC) in the United States tripled between 1975 and 2005, with much of the increase between 2000 and 2005 occurring among men 50 to 59 years. But even though incidence and mortality have increased substantially, HCC survival rates are improving, according to a report published online February 17 in the Journal of Clinical Oncology.
Researchers found that the 1-year survival rate nearly doubled between 1992 and 2005, increasing from 25% to 47%. Improvement in survival rates coincided with increasing numbers of patients being diagnosed with localized stage HCC (28% in 1992 to 1993 and 44% in 2003 to 2004).
"Early screening for patients with hepatitis C, a leading risk factor for liver cancer, has directly contributed to increasing survival rates for patients living with liver cancer," said Jennifer Obel, MD, an official of the American Society of Clinical Oncology and an attending physician at NorthShore University HealthSystem, in Illinois. Dr. Obel was not involved in the study.
"When detected early, there are significantly more treatment options for liver cancer — in most cases, the earlier it is caught, the better the prognosis," she said in a statement. "This study points to the need to identify even more at-risk individuals through early-screening programs to improve prognosis with potentially curative therapy."
Infection with chronic hepatitis C virus (HCV) or hepatitis B virus (HBV) is associated with the development of HCC. More than 3 million people are chronically infected with HCV in the United States, but chronic infection with HBV, a major global risk factor for HCC, is less common. However, among certain ethnic groups residing in the United States, the researchers note, HBV is a more common risk factor than HCV.
Etiology Complex, More Data Needed
The etiology of HCC is complex, and most likely involves interactions between multiple risk factors. In this study, Sean F. Altekruse, DVM, MPH, PhD, from the National Cancer Institute (NCI), in Bethesda, Maryland, and colleagues examined data on incidence trends, mortality rates, and survival rates from NCI's Surveillance Epidemiology and End Results (SEER) cancer registries. Their goals were to monitor changes in the burden of HCC and to define the populations most at risk, in an effort to help control the disease.
"SEER registries don't tell us the etiology, so we can only speculate on what may be driving the rates," Dr. Altekruse said in an interview. "Liver cancer typically begins with a hepatic insult, such as chronic inflammation, and then may progress to cirrhosis, and ultimately HCC."
Cancer occurs at a very late stage in the process, and Dr. Altekruse emphasized that not all patients infected with hepatitis will go through these stages, although infection with HBV and/or HCV is associated with an increased risk. "It is believed that there was an epidemic of hepatitis C that began in the 1960s and extended into the 1970s," he said. "It was projected that we would be seeing an increase in rates of HCC because of that."
But hepatitis infection is not the only risk factor. "We do need studies to better understand the proportion of HCC that is attributable to hepatitis, and we need to better understand the etiology of hepatitis C," Dr. Altekruse told Medscape Oncology. "We also need to study other possible contributing factors, such as alcohol consumption, obesity, diabetes mellitus, and iron-storage diseases."
Incidence Rising Among All Ethnic/Racial Groups
Their results showed that between 1975 and 2005 the rate of HCC tripled, from 1.6 cases to 4.9 cases per 100,000 people, and incidence was also approximately 3 times higher among men than among women during this time. Between 1992 and 2005, overall incidence rates of HCC increased, with an annual change of 4.3%.
The incidence of HCC increased among all ethnic/racial groups, with the greatest annual percentage change (APC) increase seen in the American Indian/Alaska native group (5.0%). This was followed increases in black (APC, 4.9%), white (APC, 4.6%), and Hispanic (APC, 4.0%) groups. Even though the Asian/Pacific Islander group had the highest incidence of HCC, it experienced a smaller APC (1%) than other groups. During the 5-year period from 2000 to 2005, the researchers observed marked increases in incidence rates among Hispanic, black, and white middle-aged men.
During the 1992 to 2005 time period, patterns of HCC mortality were similar to those of incidence. The overall age-adjusted mortality rates rose, with an APC of 1.6%, and mortality was highest among the Asian/Pacific Islander group, followed by Hispanic, black, American Indian/Alaska native, and white groups. Although the APC significantly increased among the Hispanic (1.7%), white (1.7%), and black (1.3%) groups, it declined for the Asian/Pacific Islander group (–0.9%). Mortality rates remained stable among the American Indian/Alaska native group.
Survival Improving in Patients With Localized Disease
An additional finding was that overall survival rates increased, and 2- to 4-year cause-specific survival rates doubled. The 1-year survival rates jumped from 65% in 1992 to 1993 to 83% in 2003 to 2004 among patients with localized HCC who reported undergoing treatment. Increases in survival were also observed among patients with localized HCC who underwent surgery, from 81% in 1992 to 1993 to 91% in 2003 to 2004.
"The most dramatic improvement in survival has been among people with localized disease," said Dr. Altekruse. "If screening can detect patients with early-stage HCC, it can truly have an important impact on the burden of liver cancer, which is projected to increase over the next 20 years."
The study was supported by the Division of Cancer Control and Population Sciences, Surveillance Research Program, National Cancer Institute, National Institutes of Health. The researchers have disclosed no relevant financial relationships.
J Clin Oncol. Published online before print February 17, 2009.
Researchers found that the 1-year survival rate nearly doubled between 1992 and 2005, increasing from 25% to 47%. Improvement in survival rates coincided with increasing numbers of patients being diagnosed with localized stage HCC (28% in 1992 to 1993 and 44% in 2003 to 2004).
"Early screening for patients with hepatitis C, a leading risk factor for liver cancer, has directly contributed to increasing survival rates for patients living with liver cancer," said Jennifer Obel, MD, an official of the American Society of Clinical Oncology and an attending physician at NorthShore University HealthSystem, in Illinois. Dr. Obel was not involved in the study.
"When detected early, there are significantly more treatment options for liver cancer — in most cases, the earlier it is caught, the better the prognosis," she said in a statement. "This study points to the need to identify even more at-risk individuals through early-screening programs to improve prognosis with potentially curative therapy."
Infection with chronic hepatitis C virus (HCV) or hepatitis B virus (HBV) is associated with the development of HCC. More than 3 million people are chronically infected with HCV in the United States, but chronic infection with HBV, a major global risk factor for HCC, is less common. However, among certain ethnic groups residing in the United States, the researchers note, HBV is a more common risk factor than HCV.
Etiology Complex, More Data Needed
The etiology of HCC is complex, and most likely involves interactions between multiple risk factors. In this study, Sean F. Altekruse, DVM, MPH, PhD, from the National Cancer Institute (NCI), in Bethesda, Maryland, and colleagues examined data on incidence trends, mortality rates, and survival rates from NCI's Surveillance Epidemiology and End Results (SEER) cancer registries. Their goals were to monitor changes in the burden of HCC and to define the populations most at risk, in an effort to help control the disease.
"SEER registries don't tell us the etiology, so we can only speculate on what may be driving the rates," Dr. Altekruse said in an interview. "Liver cancer typically begins with a hepatic insult, such as chronic inflammation, and then may progress to cirrhosis, and ultimately HCC."
Cancer occurs at a very late stage in the process, and Dr. Altekruse emphasized that not all patients infected with hepatitis will go through these stages, although infection with HBV and/or HCV is associated with an increased risk. "It is believed that there was an epidemic of hepatitis C that began in the 1960s and extended into the 1970s," he said. "It was projected that we would be seeing an increase in rates of HCC because of that."
But hepatitis infection is not the only risk factor. "We do need studies to better understand the proportion of HCC that is attributable to hepatitis, and we need to better understand the etiology of hepatitis C," Dr. Altekruse told Medscape Oncology. "We also need to study other possible contributing factors, such as alcohol consumption, obesity, diabetes mellitus, and iron-storage diseases."
Incidence Rising Among All Ethnic/Racial Groups
Their results showed that between 1975 and 2005 the rate of HCC tripled, from 1.6 cases to 4.9 cases per 100,000 people, and incidence was also approximately 3 times higher among men than among women during this time. Between 1992 and 2005, overall incidence rates of HCC increased, with an annual change of 4.3%.
The incidence of HCC increased among all ethnic/racial groups, with the greatest annual percentage change (APC) increase seen in the American Indian/Alaska native group (5.0%). This was followed increases in black (APC, 4.9%), white (APC, 4.6%), and Hispanic (APC, 4.0%) groups. Even though the Asian/Pacific Islander group had the highest incidence of HCC, it experienced a smaller APC (1%) than other groups. During the 5-year period from 2000 to 2005, the researchers observed marked increases in incidence rates among Hispanic, black, and white middle-aged men.
During the 1992 to 2005 time period, patterns of HCC mortality were similar to those of incidence. The overall age-adjusted mortality rates rose, with an APC of 1.6%, and mortality was highest among the Asian/Pacific Islander group, followed by Hispanic, black, American Indian/Alaska native, and white groups. Although the APC significantly increased among the Hispanic (1.7%), white (1.7%), and black (1.3%) groups, it declined for the Asian/Pacific Islander group (–0.9%). Mortality rates remained stable among the American Indian/Alaska native group.
Survival Improving in Patients With Localized Disease
An additional finding was that overall survival rates increased, and 2- to 4-year cause-specific survival rates doubled. The 1-year survival rates jumped from 65% in 1992 to 1993 to 83% in 2003 to 2004 among patients with localized HCC who reported undergoing treatment. Increases in survival were also observed among patients with localized HCC who underwent surgery, from 81% in 1992 to 1993 to 91% in 2003 to 2004.
"The most dramatic improvement in survival has been among people with localized disease," said Dr. Altekruse. "If screening can detect patients with early-stage HCC, it can truly have an important impact on the burden of liver cancer, which is projected to increase over the next 20 years."
The study was supported by the Division of Cancer Control and Population Sciences, Surveillance Research Program, National Cancer Institute, National Institutes of Health. The researchers have disclosed no relevant financial relationships.
J Clin Oncol. Published online before print February 17, 2009.
Hep C highest on North Coast
THE NORTH Coast has the highest rate of infection for hepatitis C in the State, despite the fact that up to 80 per cent of sufferers can be cured.
The Hepatitis C Council of NSW has found that our State houses 100,000 people infected with the disease, with the North Coast area showing the highest rates of infection at 97.4/100,000 population.
Hepatitis C is an infectious disease spread by blood-to-blood contact that can cause inflammation of the liver and lead to liver failure and cancer.
Hepatitis C Council executive officer Stuart Loveday said the need to increase treatment rates is critical.
“More than 200,000 ordinary Australians have hepatitis C, but less than two per cent of them receive treatment,” he said. “This year 10,000 more people will get hepatitis C, and most of these will be young people.”
Mr Loveday said awareness of the fact that the infection can cure 50 to 80 per cent of people undergoing treatment is low among both the community and health professionals.
“Some people are put off by treatment side effects, which can be severe for some people,” he said.
“But liver damage often occurs slowly and silently, making it very important for people to understand their options and not wait too long to consider treatment.”
The Hepatitis C Council has launched a $20,000 grants program to assist community health organisations and health workers to raise awareness about the risk, prevention and treatment of the disease.
For information, go to website www.hepatitisc.org.au.
The Hepatitis C Council of NSW has found that our State houses 100,000 people infected with the disease, with the North Coast area showing the highest rates of infection at 97.4/100,000 population.
Hepatitis C is an infectious disease spread by blood-to-blood contact that can cause inflammation of the liver and lead to liver failure and cancer.
Hepatitis C Council executive officer Stuart Loveday said the need to increase treatment rates is critical.
“More than 200,000 ordinary Australians have hepatitis C, but less than two per cent of them receive treatment,” he said. “This year 10,000 more people will get hepatitis C, and most of these will be young people.”
Mr Loveday said awareness of the fact that the infection can cure 50 to 80 per cent of people undergoing treatment is low among both the community and health professionals.
“Some people are put off by treatment side effects, which can be severe for some people,” he said.
“But liver damage often occurs slowly and silently, making it very important for people to understand their options and not wait too long to consider treatment.”
The Hepatitis C Council has launched a $20,000 grants program to assist community health organisations and health workers to raise awareness about the risk, prevention and treatment of the disease.
For information, go to website www.hepatitisc.org.au.
Combination therapy eases fibromyalgia symptoms
NEW YORK (Reuters Health) - A review of previous clinical trial results shows that a multifaceted approach can be effective for treating fibromyalgia, German researchers report.
Fibromyalgia is characterized by pain, fatigue and difficulty sleeping. It's a somewhat mysterious condition with no clear-cut cause.
Dr. Winfried Haeuser told Reuters Health that German guidelines recommend "multicomponent treatment" of fibromyalgia -- "at least two components: patient education or psychological therapy and exercise as second-line therapy for patients whose symptoms and restrictions in daily life are not sufficiently reduced by a single therapy, such as medication."
To investigate how well this strategy works, Haeuser, of Klinikum Saarbruecken, and her colleagues examined pooled evidence from nine clinical trials of multicomponent therapy involving more than 1100 patients. The researchers report the results in the medical journal Arthritis and Rheumatism.
The findings, Haeuser explained, "demonstrated that multicomponent treatment was superior to monocomponent treatment in relieving pain, depressed mood and fatigue and improving physical fitness."
However, she and her colleagues found, "There is strong evidence that the positive effects of multicomponent therapy on the key symptoms of fibromyalgia syndrome decline with time."
The longest follow-up was for 15 months. The researchers conclude, "Strategies to maintain the benefits of multicomponent treatment in the long term need to be developed."
SOURCE: Arthritis and Rheumatism, February 15, 2009.
Fibromyalgia is characterized by pain, fatigue and difficulty sleeping. It's a somewhat mysterious condition with no clear-cut cause.
Dr. Winfried Haeuser told Reuters Health that German guidelines recommend "multicomponent treatment" of fibromyalgia -- "at least two components: patient education or psychological therapy and exercise as second-line therapy for patients whose symptoms and restrictions in daily life are not sufficiently reduced by a single therapy, such as medication."
To investigate how well this strategy works, Haeuser, of Klinikum Saarbruecken, and her colleagues examined pooled evidence from nine clinical trials of multicomponent therapy involving more than 1100 patients. The researchers report the results in the medical journal Arthritis and Rheumatism.
The findings, Haeuser explained, "demonstrated that multicomponent treatment was superior to monocomponent treatment in relieving pain, depressed mood and fatigue and improving physical fitness."
However, she and her colleagues found, "There is strong evidence that the positive effects of multicomponent therapy on the key symptoms of fibromyalgia syndrome decline with time."
The longest follow-up was for 15 months. The researchers conclude, "Strategies to maintain the benefits of multicomponent treatment in the long term need to be developed."
SOURCE: Arthritis and Rheumatism, February 15, 2009.
Vertex Pharmaceuticals Strengthens HCV Drug Development Portfolio, Adds Novel Polymerase Inhibitors to Shape New Combinations with Telaprevir
Vertex to acquire privately-held ViroChem Pharma in cash and stock transaction -- Two HCV polymerase inhibitors, VCH-222 and VCH-759, have demonstrated significant antiviral activity in early clinical trials -- First STAT-C combination trial with telaprevir planned for 2H 2009 start -
CAMBRIDGE, Mass. & LAVAL, Quebec, Mar 03, 2009 (BUSINESS WIRE) -- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX), which is developing the hepatitis C virus (HCV) protease inhibitor telaprevir, will add two polymerase inhibitors to its HCV drug development portfolio through a definitive agreement to acquire privately-held ViroChem Pharma Inc. in a stock and cash transaction. With the addition of these compounds, Vertex will advance its strategy to pursue novel combinations of Specifically Targeted Antiviral Therapies for hepatitis C (STAT-Cs) for the treatment of HCV infection. Following completion of the transaction, Vertex will own worldwide rights to ViroChem's HCV drug development portfolio, including VCH-222 and VCH-759, which have demonstrated substantial reductions in plasma HCV RNA when dosed as single agents and have been well-tolerated in clinical studies to date. In particular, VCH-222 dosed as 750 mg twice daily resulted in a median 3.7 log10 decrease in HCV RNA at the end of dosing in a three-day viral kinetic study, representing the most substantial reduction in viral load reported to date with an investigational HCV polymerase inhibitor dosed as a single agent. Vertex expects to begin clinical evaluation of novel combination regimens of its HCV protease inhibitor telaprevir, currently in Phase 3 clinical development, in the second half of 2009. The transaction is subject to customary pre-closing conditions.
"This acquisition significantly strengthens our pipeline in hepatitis C by bringing together Vertex's telaprevir, our HCV protease inhibitor in registration studies, with the HCV non-nucleoside polymerase inhibitors being developed by ViroChem," said Joshua Boger, Ph.D., Chief Executive Officer of Vertex. "Through this acquisition, we're well positioned as a leader in the development of HCV therapies. Our goal is to further advance HCV care for patients through the creation of novel and highly potent STAT-C combination regimens."
"This move expands Vertex's global presence in HCV and has the potential to enhance the profile and lifecycle of our telaprevir-based combination regimens. We believe it strengthens our ability to compete and stay at the forefront in developing novel STAT-C combination regimens," added Kurt C. Graves, Executive Vice President, Chief Commercial Officer and Head, Strategic Development at Vertex. "We selected ViroChem's compounds following careful evaluation of the STAT-C landscape for more than a year. Key data has emerged that suggest that these compounds could uniquely complement telaprevir and provide a foundation for shaping a potentially new treatment paradigm."
ViroChem HCV Drug Development Portfolio
Two ViroChem HCV polymerase inhibitors, VCH-222 and VCH-759, are currently in clinical development. ViroChem also has a preclinical program directed at the discovery of novel HCV NS5a inhibitors. The status and profile of each clinical compound is detailed below.
VCH-222: VCH-222 is an oral non-nucleoside inhibitor of the HCV NS5B polymerase that recently completed a viral kinetic study in HCV patients. In this study involving five treatment-naive genotype 1a and 1b HCV infected patients, VCH-222 dosed as 750 mg twice daily resulted in a median 3.7 log10 decrease in HCV RNA - equivalent to a 5,000-fold reduction in virus in the blood - at the end of three days of dosing. The results were consistent from patient to patient, and across HCV genotype 1 subtypes, and represent the most substantial reduction in viral load reported to date with an investigational HCV polymerase inhibitor dosed as a single agent. In clinical evaluations to date, VCH-222 has been well-tolerated, with no serious adverse events observed. VCH-222 has completed 28-day non-clinical toxicology studies in two species.
VCH-759: VCH-759 is an oral non-nucleoside inhibitor of the HCV NS5B polymerase that has completed Phase 1b clinical development. In a Phase 1b trial reported at a medical conference in 2007, VCH-759 dosed as 800 mg three times daily showed a mean maximal 2.5 log10 reduction in HCV RNA and a median 1.7 log10 reduction in HCV RNA at the end of 10 days. VCH-759 was also well-tolerated with no serious adverse events observed in clinical studies to date. VCH-759 has completed 28-day non-clinical toxicology studies.
Future clinical plans: Vertex plans to conduct additional dose-ranging studies of VCH-222 as a single agent and in combination with pegylated interferon and ribavirin. Vertex plans to initiate a first clinical study combining telaprevir with a ViroChem HCV polymerase inhibitor in the second half of 2009. Data from in vitro HCV replicon studies suggest that VCH-222 and VCH-759 may provide synergistic or additive antiviral activity to the HCV protease inhibitor telaprevir, thus creating the potential for a non-cross resistant, complementary profile in exploratory clinical studies.
Terms of the Transaction
Under the terms of the agreement, which have been approved by the Boards of Directors of both companies, ViroChem shareholders will receive $100 million in cash and 9.9 million shares of Vertex common stock. The stock portion of the consideration is subject to a collar, and the actual number of shares of Vertex stock to be issued will be based on an average Vertex share price prior to the acquisition closing, but per the agreement will not exceed 11.0 million shares. Vertex expects the shares issued in this transaction will be immediately tradeable under a resale registration statement which Vertex plans to file at the time of closing. Goldman, Sachs & Co. is acting as exclusive financial advisor to Vertex.
Vertex HCV Portfolio
Vertex is developing telaprevir, one of the most advanced investigational agents in development that specifically targets HCV. Telaprevir is being evaluated in a broad Phase 3 registration program, which has enrolled more than 2,200 genotype 1 HCV patients, including patients who have both failed prior treatment with pegylated interferon and ribavirin, as well as patients who are naive to treatment. Vertex plans to file an NDA for telaprevir in the second half of 2010 assuming successful completion of its ongoing Phase 3 program. In addition, Vertex is developing two other novel HCV protease inhibitors, VX-813 and VX-985, currently in Phase 1 and preclinical development respectively.
Vertex retains commercial rights to telaprevir in North America. Vertex and Tibotec are collaborating to develop and commercialize telaprevir in Europe, South America, Australia, the Middle East, and other countries. Vertex is collaborating with Mitsubishi Tanabe Pharma Corporation to develop and commercialize telaprevir in Japan and certain Far East countries. Vertex retains worldwide rights to VX-813 and VX-985.
HCV Protease and Polymerase as Targets for New Drug Development
Since the identification and sequencing of the hepatitis C virus in 1989, efforts to discover new drugs for HCV infection have focused on specific antiviral targets, including the HCV NS3 protease and the HCV NS5B polymerase. Several specifically targeted antiviral therapies for HCV (known as STAT-Cs) have demonstrated promising clinical results, with the potential for a significant advancement in HCV treatment and disease outcomes when dosed in combination with the currently available treatment of pegylated interferon and ribavirin. As investigational compounds targeting HCV protease and polymerase have advanced in development, clinicians have expressed interest in combining these investigational approaches, with the goal of further optimizing HCV treatment regimens, including treatment of certain hard to treat populations, by potentially increasing SVR rates, decreasing the duration of HCV therapy and increasing the tolerability of HCV treatment regimens.
About Vertex
Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company's strategy is to commercialize its products both independently and in collaboration with major pharmaceutical companies. Vertex's product pipeline is focused on viral diseases, cystic fibrosis, inflammation, autoimmune diseases, cancer, and pain. Vertex co-discovered the HIV protease inhibitor, Lexiva, with GlaxoSmithKline.
Lexiva is a registered trademark of the GlaxoSmithKline group of companies.
Vertex's press releases are available at www.vrtx.com.
Conference Call
Vertex Pharmaceuticals will host a conference call and webcast on Tuesday, March 3, 2009 at 5:15 p.m. EST to review recent developments. This call and webcast will be broadcast via the Internet at www.vrtx.com. It is suggested that webcast participants go to the web site at least 10 minutes in advance of the call to ensure that they can access the slides. The link to the webcast is available on the Events and Presentations button on the home page.
To listen to the call on the telephone, dial (800) 374-0296 (U.S. and Canada) or (702) 696-4937 (International) and the conference ID number is 88366180. Vertex is also providing a podcast MP3 file available for download on the Vertex website at www.vrtx.com.
The call will be available for replay via telephone commencing March 3, 2009 at 8:00 p.m. EST running through 5:00 p.m. EST on March 9, 2009. The replay phone number for the U.S. and Canada is (800) 642-1687. The international replay number is (706) 645-9291 and the conference ID number is 88366180. Following the live webcast, an archived version will be available on Vertex's website until 5:00 p.m. EST on March 16, 2009.
Vertex Pharmaceuticals IncorporatedInvestorsMichael Partridge, 617-444-6108orLora Pike, 617-444-6755orMediaJane Kramer, 617-444-6924orZachry Barber, 617-444-6470
SOURCE: Vertex Pharmaceuticals Incorporated
CAMBRIDGE, Mass. & LAVAL, Quebec, Mar 03, 2009 (BUSINESS WIRE) -- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX), which is developing the hepatitis C virus (HCV) protease inhibitor telaprevir, will add two polymerase inhibitors to its HCV drug development portfolio through a definitive agreement to acquire privately-held ViroChem Pharma Inc. in a stock and cash transaction. With the addition of these compounds, Vertex will advance its strategy to pursue novel combinations of Specifically Targeted Antiviral Therapies for hepatitis C (STAT-Cs) for the treatment of HCV infection. Following completion of the transaction, Vertex will own worldwide rights to ViroChem's HCV drug development portfolio, including VCH-222 and VCH-759, which have demonstrated substantial reductions in plasma HCV RNA when dosed as single agents and have been well-tolerated in clinical studies to date. In particular, VCH-222 dosed as 750 mg twice daily resulted in a median 3.7 log10 decrease in HCV RNA at the end of dosing in a three-day viral kinetic study, representing the most substantial reduction in viral load reported to date with an investigational HCV polymerase inhibitor dosed as a single agent. Vertex expects to begin clinical evaluation of novel combination regimens of its HCV protease inhibitor telaprevir, currently in Phase 3 clinical development, in the second half of 2009. The transaction is subject to customary pre-closing conditions.
"This acquisition significantly strengthens our pipeline in hepatitis C by bringing together Vertex's telaprevir, our HCV protease inhibitor in registration studies, with the HCV non-nucleoside polymerase inhibitors being developed by ViroChem," said Joshua Boger, Ph.D., Chief Executive Officer of Vertex. "Through this acquisition, we're well positioned as a leader in the development of HCV therapies. Our goal is to further advance HCV care for patients through the creation of novel and highly potent STAT-C combination regimens."
"This move expands Vertex's global presence in HCV and has the potential to enhance the profile and lifecycle of our telaprevir-based combination regimens. We believe it strengthens our ability to compete and stay at the forefront in developing novel STAT-C combination regimens," added Kurt C. Graves, Executive Vice President, Chief Commercial Officer and Head, Strategic Development at Vertex. "We selected ViroChem's compounds following careful evaluation of the STAT-C landscape for more than a year. Key data has emerged that suggest that these compounds could uniquely complement telaprevir and provide a foundation for shaping a potentially new treatment paradigm."
ViroChem HCV Drug Development Portfolio
Two ViroChem HCV polymerase inhibitors, VCH-222 and VCH-759, are currently in clinical development. ViroChem also has a preclinical program directed at the discovery of novel HCV NS5a inhibitors. The status and profile of each clinical compound is detailed below.
VCH-222: VCH-222 is an oral non-nucleoside inhibitor of the HCV NS5B polymerase that recently completed a viral kinetic study in HCV patients. In this study involving five treatment-naive genotype 1a and 1b HCV infected patients, VCH-222 dosed as 750 mg twice daily resulted in a median 3.7 log10 decrease in HCV RNA - equivalent to a 5,000-fold reduction in virus in the blood - at the end of three days of dosing. The results were consistent from patient to patient, and across HCV genotype 1 subtypes, and represent the most substantial reduction in viral load reported to date with an investigational HCV polymerase inhibitor dosed as a single agent. In clinical evaluations to date, VCH-222 has been well-tolerated, with no serious adverse events observed. VCH-222 has completed 28-day non-clinical toxicology studies in two species.
VCH-759: VCH-759 is an oral non-nucleoside inhibitor of the HCV NS5B polymerase that has completed Phase 1b clinical development. In a Phase 1b trial reported at a medical conference in 2007, VCH-759 dosed as 800 mg three times daily showed a mean maximal 2.5 log10 reduction in HCV RNA and a median 1.7 log10 reduction in HCV RNA at the end of 10 days. VCH-759 was also well-tolerated with no serious adverse events observed in clinical studies to date. VCH-759 has completed 28-day non-clinical toxicology studies.
Future clinical plans: Vertex plans to conduct additional dose-ranging studies of VCH-222 as a single agent and in combination with pegylated interferon and ribavirin. Vertex plans to initiate a first clinical study combining telaprevir with a ViroChem HCV polymerase inhibitor in the second half of 2009. Data from in vitro HCV replicon studies suggest that VCH-222 and VCH-759 may provide synergistic or additive antiviral activity to the HCV protease inhibitor telaprevir, thus creating the potential for a non-cross resistant, complementary profile in exploratory clinical studies.
Terms of the Transaction
Under the terms of the agreement, which have been approved by the Boards of Directors of both companies, ViroChem shareholders will receive $100 million in cash and 9.9 million shares of Vertex common stock. The stock portion of the consideration is subject to a collar, and the actual number of shares of Vertex stock to be issued will be based on an average Vertex share price prior to the acquisition closing, but per the agreement will not exceed 11.0 million shares. Vertex expects the shares issued in this transaction will be immediately tradeable under a resale registration statement which Vertex plans to file at the time of closing. Goldman, Sachs & Co. is acting as exclusive financial advisor to Vertex.
Vertex HCV Portfolio
Vertex is developing telaprevir, one of the most advanced investigational agents in development that specifically targets HCV. Telaprevir is being evaluated in a broad Phase 3 registration program, which has enrolled more than 2,200 genotype 1 HCV patients, including patients who have both failed prior treatment with pegylated interferon and ribavirin, as well as patients who are naive to treatment. Vertex plans to file an NDA for telaprevir in the second half of 2010 assuming successful completion of its ongoing Phase 3 program. In addition, Vertex is developing two other novel HCV protease inhibitors, VX-813 and VX-985, currently in Phase 1 and preclinical development respectively.
Vertex retains commercial rights to telaprevir in North America. Vertex and Tibotec are collaborating to develop and commercialize telaprevir in Europe, South America, Australia, the Middle East, and other countries. Vertex is collaborating with Mitsubishi Tanabe Pharma Corporation to develop and commercialize telaprevir in Japan and certain Far East countries. Vertex retains worldwide rights to VX-813 and VX-985.
HCV Protease and Polymerase as Targets for New Drug Development
Since the identification and sequencing of the hepatitis C virus in 1989, efforts to discover new drugs for HCV infection have focused on specific antiviral targets, including the HCV NS3 protease and the HCV NS5B polymerase. Several specifically targeted antiviral therapies for HCV (known as STAT-Cs) have demonstrated promising clinical results, with the potential for a significant advancement in HCV treatment and disease outcomes when dosed in combination with the currently available treatment of pegylated interferon and ribavirin. As investigational compounds targeting HCV protease and polymerase have advanced in development, clinicians have expressed interest in combining these investigational approaches, with the goal of further optimizing HCV treatment regimens, including treatment of certain hard to treat populations, by potentially increasing SVR rates, decreasing the duration of HCV therapy and increasing the tolerability of HCV treatment regimens.
About Vertex
Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company's strategy is to commercialize its products both independently and in collaboration with major pharmaceutical companies. Vertex's product pipeline is focused on viral diseases, cystic fibrosis, inflammation, autoimmune diseases, cancer, and pain. Vertex co-discovered the HIV protease inhibitor, Lexiva, with GlaxoSmithKline.
Lexiva is a registered trademark of the GlaxoSmithKline group of companies.
Vertex's press releases are available at www.vrtx.com.
Conference Call
Vertex Pharmaceuticals will host a conference call and webcast on Tuesday, March 3, 2009 at 5:15 p.m. EST to review recent developments. This call and webcast will be broadcast via the Internet at www.vrtx.com. It is suggested that webcast participants go to the web site at least 10 minutes in advance of the call to ensure that they can access the slides. The link to the webcast is available on the Events and Presentations button on the home page.
To listen to the call on the telephone, dial (800) 374-0296 (U.S. and Canada) or (702) 696-4937 (International) and the conference ID number is 88366180. Vertex is also providing a podcast MP3 file available for download on the Vertex website at www.vrtx.com.
The call will be available for replay via telephone commencing March 3, 2009 at 8:00 p.m. EST running through 5:00 p.m. EST on March 9, 2009. The replay phone number for the U.S. and Canada is (800) 642-1687. The international replay number is (706) 645-9291 and the conference ID number is 88366180. Following the live webcast, an archived version will be available on Vertex's website until 5:00 p.m. EST on March 16, 2009.
Vertex Pharmaceuticals IncorporatedInvestorsMichael Partridge, 617-444-6108orLora Pike, 617-444-6755orMediaJane Kramer, 617-444-6924orZachry Barber, 617-444-6470
SOURCE: Vertex Pharmaceuticals Incorporated
Q&A: could I catch hepatitis C?
How easy is it to catch hepatitis C from a partner who is carrying the virus? I have just heard that an ex of mine has it
Dr Mark Porter
How easy is it to catch hepatitis C from a partner who is carrying the virus? I have just heard that a past boyfriend of mine is awaiting a liver transplant because of the infection, which he probably picked up when he dabbled with drugs at university. That was more than 15 years ago, but I am now worried that he may have had the virus when we were together and passed it on to me.
Hepatitis C is an infection that was first identified in 1989. Some people will eliminate the virus without any trouble, but most develop a slow-burning, chronic infection that, in as many as one in five people, can lead to serious liver disease some 20 years later.
Hep C is blood borne and the most common route of transmission in the UK is sharing dirty needles and syringes. There is also a risk to anyone who received a blood transfusion before routine screening was introduced in 1991, or blood products (as used to treat people with haemophilia) before 1986.
In theory the virus can be spread during any activity where blood may come into contact with cuts or a nick in the skin but sexual transmission is quite uncommon. Studies suggest that fewer than one in twenty regular sexual partners of people with Hep C become infected themselves: good odds for you.
Screening involves a simple blood test and if you turn out to have the virus, there are treatments that can clear the infection in around half of cases, but the earlier this is done the better. Visit www.nhs.uk/hepc for more details.
Dr Mark Porter
How easy is it to catch hepatitis C from a partner who is carrying the virus? I have just heard that a past boyfriend of mine is awaiting a liver transplant because of the infection, which he probably picked up when he dabbled with drugs at university. That was more than 15 years ago, but I am now worried that he may have had the virus when we were together and passed it on to me.
Hepatitis C is an infection that was first identified in 1989. Some people will eliminate the virus without any trouble, but most develop a slow-burning, chronic infection that, in as many as one in five people, can lead to serious liver disease some 20 years later.
Hep C is blood borne and the most common route of transmission in the UK is sharing dirty needles and syringes. There is also a risk to anyone who received a blood transfusion before routine screening was introduced in 1991, or blood products (as used to treat people with haemophilia) before 1986.
In theory the virus can be spread during any activity where blood may come into contact with cuts or a nick in the skin but sexual transmission is quite uncommon. Studies suggest that fewer than one in twenty regular sexual partners of people with Hep C become infected themselves: good odds for you.
Screening involves a simple blood test and if you turn out to have the virus, there are treatments that can clear the infection in around half of cases, but the earlier this is done the better. Visit www.nhs.uk/hepc for more details.
Study Showing Improved Virologic Response with Nitazoxanide in Chronic Hepatitis C Published in Gastroenterology
Editorial Accompanies Manuscript in March Issue
TAMPA, Fla., March 2 /PRNewswire/ -- A study evaluating nitazoxanide in combination with peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C virus (HCV) infection with genotype 4 was published in the March issue of Gastroenterology, the official journal of the American Gastroenterological Association Institute (AGA Institute). The study showed that the addition of nitazoxanide to standard-of-care therapy increased the rate of sustained virologic response when compared with patients given peginterferon plus ribavirin alone.(1) An accompanying editorial commenting on the study was also published in the Journal.(2)
"The results published today in Gastroenterology represent an important milestone in the development of nitazoxanide, the first thiazolide, for the treatment of chronic hepatitis C," said Jean-Francois Rossignol, MD, PhD, Romark Institute for Medical Research, the inventor of this new class of antiviral drugs and lead author of the study. "Nitazoxanide is currently being evaluated along with the standard-of-care treatment in patients with chronic hepatitis C genotype 1 in clinical trials in the U.S., and we look forward to reporting interim data from those trials in the coming months."
Study Details
The randomized, controlled study published in Gastroenterology evaluated the safety and efficacy of nitazoxanide plus peginterferon, with or without ribavirin, in 97 patients with previously untreated genotype 4 chronic hepatitis C at 2 centers in Egypt. Participants were sequentially allocated into 3 treatment arms (one patient immediately dropped from the study):
* Peginterferon alfa-2a 180 mcg/week plus ribavirin 1000-1200 mg/day for 48 weeks (standard of care) (n = 40);
* Nitazoxanide 500 mg twice daily monotherapy for 12 weeks followed by nitazoxanide plus peginterferon for an additional 36 weeks (n = 28);
* Nitazoxanide monotherapy for 12 weeks followed by nitazoxanide plus both peginterferon and ribavirin for 36 weeks (n = 28).
The primary endpoint was sustained virological response (SVR), or serum HCV RNA <12 IU/mL 24 weeks after the end of treatment. Secondary endpoints included HCV RNA <12 IU/mL at week 4 (rapid virological response, or RVR), at week 12 (complete early virological response, cEVR), and at the end-of-treatment (ETR).
Results
The percentages of patients with RVR, defined as undetectable serum HCV RNA at week 4 of combination therapy, and SVR were significantly higher in patients given the triple therapy compared with the standard of care (64% versus 38%, p=0.048 and 79% versus 50%, p=0.023, respectively). Patients given nitazoxanide plus peginterferon alfa-2a had intermediate rates of RVR (54%) and SVR (61%). Adverse events were similar across treatment groups except for a higher rate of anemia in the groups receiving ribavirin. In the nitazoxanide group, virologic responses were maintained through the end of treatment with no virologic breakthroughs. Of note, the use of nitazoxanide was associated with reduced relapse rates (3/20 patients in the peginterferon plus nitazoxanide arm, and 1/23 patients in the triple arm with peginterferon, ribavirin and nitazoxanide) versus 10/30 patients in the standard-of-care arm.
About Nitazoxanide and Hepatitis C
Nitazoxanide, the first of a new class of broad spectrum antiviral drugs known as the thiazolides, is undergoing worldwide development as a treatment of chronic hepatitis C. Nitazoxanide is a potent inhibitor of hepatitis C virus (HCV) replication in HCV genotype 1-derived replicon cell lines, and in vitro studies have shown that it does not induce mutations in the virus that confer resistance. Phase II clinical trials are ongoing in the United States in patients with chronic hepatitis C and genotype 1 infection.
A recent Phase II study of low and high doses of a controlled-release nitazoxanide tablet showed favorable pharmacokinetics and significant reduction in viral load, with good tolerability and safety.(3) Romark recently entered into an agreement granting Chugai Pharmaceutical Co., Ltd., a member of the Roche Group, an exclusive license to develop and market nitazoxanide for the treatment of chronic hepatitis C in Japan.
About Romark Laboratories
Romark Laboratories (www.romark.com), a privately held biopharmaceutical company, has discovered and developed a new class of small molecule antivirals known as thiazolides. The Company is developing nitazoxanide, the first of the thiazolide class, for the treatment of chronic hepatitis C, and is developing other new thiazolides for treating viral diseases including chronic hepatitis B. Alinia(R) (nitazoxanide) is approved by the U.S. Food and Drug Administration and marketed by Romark for the treatment of infections caused by Cryptosporidium or Giardia.
(1)"Improved Virologic Response in Chronic Hepatitis C Genotype 4 Patients Given Nitazoxanide, Peginterferon and Ribavirin," J.F. Rossignol, M.D. et. al., Gastroenterology, Vol. 136 issue 3, pp 856-862, March 2009
(2)"Nitazoxanide: Beyond Parasites Toward a Novel Agent for Hepatitis C," Jama M. Darling, Michael W. Fried, Gastroenterology Vol. 136 issue 3, pp 760-763, March 2009
(3)"Controlled Release Tablet Improves Pharmacokinetics, Viral Kinetics and Tolerability of Nitazoxanide for Treatment of Chronic Hepatitis C," Emmet B. Keeffe, M.D., of the Romark Institute for Medical Research, Tampa, FL. 19th Conference of the Asian Pacific Association for the Study of the Liver (APASL), abstract FP052, February 14, 2009
SOURCE Romark Laboratories
TAMPA, Fla., March 2 /PRNewswire/ -- A study evaluating nitazoxanide in combination with peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C virus (HCV) infection with genotype 4 was published in the March issue of Gastroenterology, the official journal of the American Gastroenterological Association Institute (AGA Institute). The study showed that the addition of nitazoxanide to standard-of-care therapy increased the rate of sustained virologic response when compared with patients given peginterferon plus ribavirin alone.(1) An accompanying editorial commenting on the study was also published in the Journal.(2)
"The results published today in Gastroenterology represent an important milestone in the development of nitazoxanide, the first thiazolide, for the treatment of chronic hepatitis C," said Jean-Francois Rossignol, MD, PhD, Romark Institute for Medical Research, the inventor of this new class of antiviral drugs and lead author of the study. "Nitazoxanide is currently being evaluated along with the standard-of-care treatment in patients with chronic hepatitis C genotype 1 in clinical trials in the U.S., and we look forward to reporting interim data from those trials in the coming months."
Study Details
The randomized, controlled study published in Gastroenterology evaluated the safety and efficacy of nitazoxanide plus peginterferon, with or without ribavirin, in 97 patients with previously untreated genotype 4 chronic hepatitis C at 2 centers in Egypt. Participants were sequentially allocated into 3 treatment arms (one patient immediately dropped from the study):
* Peginterferon alfa-2a 180 mcg/week plus ribavirin 1000-1200 mg/day for 48 weeks (standard of care) (n = 40);
* Nitazoxanide 500 mg twice daily monotherapy for 12 weeks followed by nitazoxanide plus peginterferon for an additional 36 weeks (n = 28);
* Nitazoxanide monotherapy for 12 weeks followed by nitazoxanide plus both peginterferon and ribavirin for 36 weeks (n = 28).
The primary endpoint was sustained virological response (SVR), or serum HCV RNA <12 IU/mL 24 weeks after the end of treatment. Secondary endpoints included HCV RNA <12 IU/mL at week 4 (rapid virological response, or RVR), at week 12 (complete early virological response, cEVR), and at the end-of-treatment (ETR).
Results
The percentages of patients with RVR, defined as undetectable serum HCV RNA at week 4 of combination therapy, and SVR were significantly higher in patients given the triple therapy compared with the standard of care (64% versus 38%, p=0.048 and 79% versus 50%, p=0.023, respectively). Patients given nitazoxanide plus peginterferon alfa-2a had intermediate rates of RVR (54%) and SVR (61%). Adverse events were similar across treatment groups except for a higher rate of anemia in the groups receiving ribavirin. In the nitazoxanide group, virologic responses were maintained through the end of treatment with no virologic breakthroughs. Of note, the use of nitazoxanide was associated with reduced relapse rates (3/20 patients in the peginterferon plus nitazoxanide arm, and 1/23 patients in the triple arm with peginterferon, ribavirin and nitazoxanide) versus 10/30 patients in the standard-of-care arm.
About Nitazoxanide and Hepatitis C
Nitazoxanide, the first of a new class of broad spectrum antiviral drugs known as the thiazolides, is undergoing worldwide development as a treatment of chronic hepatitis C. Nitazoxanide is a potent inhibitor of hepatitis C virus (HCV) replication in HCV genotype 1-derived replicon cell lines, and in vitro studies have shown that it does not induce mutations in the virus that confer resistance. Phase II clinical trials are ongoing in the United States in patients with chronic hepatitis C and genotype 1 infection.
A recent Phase II study of low and high doses of a controlled-release nitazoxanide tablet showed favorable pharmacokinetics and significant reduction in viral load, with good tolerability and safety.(3) Romark recently entered into an agreement granting Chugai Pharmaceutical Co., Ltd., a member of the Roche Group, an exclusive license to develop and market nitazoxanide for the treatment of chronic hepatitis C in Japan.
About Romark Laboratories
Romark Laboratories (www.romark.com), a privately held biopharmaceutical company, has discovered and developed a new class of small molecule antivirals known as thiazolides. The Company is developing nitazoxanide, the first of the thiazolide class, for the treatment of chronic hepatitis C, and is developing other new thiazolides for treating viral diseases including chronic hepatitis B. Alinia(R) (nitazoxanide) is approved by the U.S. Food and Drug Administration and marketed by Romark for the treatment of infections caused by Cryptosporidium or Giardia.
(1)"Improved Virologic Response in Chronic Hepatitis C Genotype 4 Patients Given Nitazoxanide, Peginterferon and Ribavirin," J.F. Rossignol, M.D. et. al., Gastroenterology, Vol. 136 issue 3, pp 856-862, March 2009
(2)"Nitazoxanide: Beyond Parasites Toward a Novel Agent for Hepatitis C," Jama M. Darling, Michael W. Fried, Gastroenterology Vol. 136 issue 3, pp 760-763, March 2009
(3)"Controlled Release Tablet Improves Pharmacokinetics, Viral Kinetics and Tolerability of Nitazoxanide for Treatment of Chronic Hepatitis C," Emmet B. Keeffe, M.D., of the Romark Institute for Medical Research, Tampa, FL. 19th Conference of the Asian Pacific Association for the Study of the Liver (APASL), abstract FP052, February 14, 2009
SOURCE Romark Laboratories
High hepatitis C viral load increases risk of death in HIV/HCV coinfected patients
A high level of hepatitis C virus (HCV) in the blood is associated with an increased risk of death in HIV/HCV coinfected individuals, according to data presented on February 10th at the Sixteenth Conference on Retroviruses and Opportunistic Infections in Montreal, Canada.
Jürgen Rockstroh from the University of Bonn in Germany presented results from a study evaluating the influence of HCV viral load and genotype on disease progression and response to antiretroviral therapy amongst all HIV/HCV coinfected participants in EuroSIDA, a prospective observational cohort of more than 16,000 HIV-positive individuals from more than 30 mostly European countries.
Having previously shown that being HCV antibody-positive was not associated with increased mortality amongst people with HIV, the investigators looked at rates of death due to any cause and due to liver-related disease, comparing coinfected people with high (500,000 IU/ml or more), low (less than 500,000 IU/ml) and undetectable (less that 615 IU/ml) HCV viral load, and those with HCV genotypes 1, 2, 3 and 4.
Out of 1952 identified HIV/HCV coinfected cohort members, 821 (42%) fell into the high HCV viral load group, 716 (37%) fell into the low HCV group, and 415 (21%) had undetectable HCV. Amongst the 1537 participants with measurable HCV, just over half had hard to treat genotype 1, nearly one-third had genotype 3, about 14% had genotype 4 and only 3% had genotype 2. Very few (about 2%) had taken interferon-based therapy for hepatitis C, though the numbers increased over time.
A total of 78 people in the undetectable HCV viral load group died due to any cause compared with 96 in the low HCV group and 158 in the high HCV group. All-cause mortality rates for the three groups were 3.12, 1.74, and 4.17 per 100 person-years, respectively.
A similar pattern was seen for deaths due to liver disease, though the numbers were smaller: 17 people in the undetectable HCV group died due to liver-related causes compared with 32 in the low HCV group and 49 in the high HCV group, translating to rates of 0.68, 0.58, and 1.29 deaths per 100 person-years, respectively.
After adjusting for potential confounding factors including sex, age, race/ethnicity, HIV transmission risk group, immune status (CD4 cell count and history of AIDS diagnosis), type of antiretroviral therapy, region of Europe, and triple infection with hepatitis B, people with undetectable and low HCV viral load had similar rates of death due to any cause, but the rate was nearly doubled in the high HCV group (adjusted incidence rate ratio of 1.94).
Restricting the adjusted analysis to liver-related deaths, people with undetectable and low HCV viral load again had statistically similar liver-related mortality rates, whilst those in the high HCV group were 77% more likely than to die of such cause than those in the low viral load group (adjusted incidence rate ratio of 1.77).
After adjustment, people with HCV genotypes 2 and 3 had a lower rate of all-cause death than those with genotype 1, but this was only significant for genotype 3. A similar pattern was seen for liver-related deaths, but differences did not reach statistical significance, possibly due to small numbers. This finding is noteworthy because HCV genotype 3 is associated with liver steatosis (fat accumulation), which might be expected to predict worse outcomes.
In addition, Dr Rockstroh reported that HCV viral load level was not correlated with differences in response to antiretroviral therapy, either HIV suppression or CD4 cell recovery. However, people with HCV genotypes other than 1 had poorer virological and immunological response to anti-HIV therapy, reaching statistical significance for genotype 4 - a finding he said has not been observed in HIV-negative hepatitis C patients.
These findings prompted some debate, as prior research in HIV-negative people with hepatitis C has not revealed a link between HCV viral load or genotype and liver disease progression.
Dr Rockstroh acknowledged that mortality rates were not adjusted for fibrosis stage in this analysis, as this information was not generally available (it is now being collected). Assessment of alcohol use, he added, is "extremely difficult" in this type of observational study.
In closing, Dr Rockstroh suggested that the effect of HCV viral load on mortality may be more apparent in HIV-positive individuals, who tend to have higher HCV RNA levels and more rapid liver disease progression than HIV-negative hepatitis C patients.
Reference
Rockstroh J et al. High HCV is associated with an increased risk for mortality in HIV/HCV-co-infected individuals. Sixteenth Conference on Retroviruses and Opportunistic Infections, Montreal, abstract 101, 2009.
Jürgen Rockstroh from the University of Bonn in Germany presented results from a study evaluating the influence of HCV viral load and genotype on disease progression and response to antiretroviral therapy amongst all HIV/HCV coinfected participants in EuroSIDA, a prospective observational cohort of more than 16,000 HIV-positive individuals from more than 30 mostly European countries.
Having previously shown that being HCV antibody-positive was not associated with increased mortality amongst people with HIV, the investigators looked at rates of death due to any cause and due to liver-related disease, comparing coinfected people with high (500,000 IU/ml or more), low (less than 500,000 IU/ml) and undetectable (less that 615 IU/ml) HCV viral load, and those with HCV genotypes 1, 2, 3 and 4.
Out of 1952 identified HIV/HCV coinfected cohort members, 821 (42%) fell into the high HCV viral load group, 716 (37%) fell into the low HCV group, and 415 (21%) had undetectable HCV. Amongst the 1537 participants with measurable HCV, just over half had hard to treat genotype 1, nearly one-third had genotype 3, about 14% had genotype 4 and only 3% had genotype 2. Very few (about 2%) had taken interferon-based therapy for hepatitis C, though the numbers increased over time.
A total of 78 people in the undetectable HCV viral load group died due to any cause compared with 96 in the low HCV group and 158 in the high HCV group. All-cause mortality rates for the three groups were 3.12, 1.74, and 4.17 per 100 person-years, respectively.
A similar pattern was seen for deaths due to liver disease, though the numbers were smaller: 17 people in the undetectable HCV group died due to liver-related causes compared with 32 in the low HCV group and 49 in the high HCV group, translating to rates of 0.68, 0.58, and 1.29 deaths per 100 person-years, respectively.
After adjusting for potential confounding factors including sex, age, race/ethnicity, HIV transmission risk group, immune status (CD4 cell count and history of AIDS diagnosis), type of antiretroviral therapy, region of Europe, and triple infection with hepatitis B, people with undetectable and low HCV viral load had similar rates of death due to any cause, but the rate was nearly doubled in the high HCV group (adjusted incidence rate ratio of 1.94).
Restricting the adjusted analysis to liver-related deaths, people with undetectable and low HCV viral load again had statistically similar liver-related mortality rates, whilst those in the high HCV group were 77% more likely than to die of such cause than those in the low viral load group (adjusted incidence rate ratio of 1.77).
After adjustment, people with HCV genotypes 2 and 3 had a lower rate of all-cause death than those with genotype 1, but this was only significant for genotype 3. A similar pattern was seen for liver-related deaths, but differences did not reach statistical significance, possibly due to small numbers. This finding is noteworthy because HCV genotype 3 is associated with liver steatosis (fat accumulation), which might be expected to predict worse outcomes.
In addition, Dr Rockstroh reported that HCV viral load level was not correlated with differences in response to antiretroviral therapy, either HIV suppression or CD4 cell recovery. However, people with HCV genotypes other than 1 had poorer virological and immunological response to anti-HIV therapy, reaching statistical significance for genotype 4 - a finding he said has not been observed in HIV-negative hepatitis C patients.
These findings prompted some debate, as prior research in HIV-negative people with hepatitis C has not revealed a link between HCV viral load or genotype and liver disease progression.
Dr Rockstroh acknowledged that mortality rates were not adjusted for fibrosis stage in this analysis, as this information was not generally available (it is now being collected). Assessment of alcohol use, he added, is "extremely difficult" in this type of observational study.
In closing, Dr Rockstroh suggested that the effect of HCV viral load on mortality may be more apparent in HIV-positive individuals, who tend to have higher HCV RNA levels and more rapid liver disease progression than HIV-negative hepatitis C patients.
Reference
Rockstroh J et al. High HCV is associated with an increased risk for mortality in HIV/HCV-co-infected individuals. Sixteenth Conference on Retroviruses and Opportunistic Infections, Montreal, abstract 101, 2009.
How Inflammatory Disease Causes Fatigue
ScienceDaily (Feb. 28, 2009) — New animal research in the February 18 issue of The Journal of Neuroscience may indicate how certain diseases make people feel so tired and listless. Although the brain is usually isolated from the immune system, the study suggests that certain behavioral changes suffered by those with chronic inflammatory diseases are caused by the infiltration of immune cells into the brain. The findings suggest possible new treatment avenues to improve patients' quality of life.
Chronic inflammatory diseases like rheumatoid arthritis, inflammatory bowel disease, psoriasis, and liver disease cause "sickness behaviors," including fatigue, malaise, and loss of social interest. However, it has been unclear how inflammation in other organs in the body can impact the brain and behavior.
The researchers found that in mice with inflamed livers, white blood cells called monocytes infiltrated the brain. These findings support previous research demonstrating the presence of immune cells in the brain following organ inflammation, challenging the long-held belief that the blood-brain barrier prevents immune cells from accessing the brain.
"Using an experimental model of liver inflammation, our group has demonstrated for the first time the existence of a novel communication pathway between the inflamed liver and the brain," said the study's senior author Mark Swain, MD, Professor of Medicine at the University of Calgary.
Swain and his colleagues found that liver inflammation triggered brain cells called microglia to produce CCL2, a chemical that attracts monocytes. When the researchers blocked CCL2 signaling, monocytes did not enter the brain despite ongoing inflammation in the liver.
Liver inflammation also stimulated cells in the blood to make an immune chemical (TNFα). When the researchers blocked the signaling of this immune chemical, microglia produced less CCL2, and monocytes stayed out of the brain.
In the mice with inflamed livers, preventing the entry of monocytes into the brain reduced sickness behaviors; mice showed more mobility and social interaction. These findings suggest that people with chronic inflammatory diseases may benefit from treatments that limit monocyte access to the brain.
"Sickness behavior significantly impacts quality of life. Our findings further our understanding and may generate potential new avenues for treatment of these often crippling symptoms," said Swain.
"The brain is the master coordinator of many of our bodies' defense responses, so it must be able to sense injury and inflammation in distant body organs. This study starts to explain the peripheral communication signals that activate the brain," said Nancy Rothwell, PhD, DSc, at the University of Manchester, an expert on brain inflammation who is unaffiliated with the study.
The research was supported by the Canadian Institutes of Health Research, the Canadian Liver Foundation, and the Alberta Heritage Foundation for Medical Research.
Adapted from materials provided by Society for Neuroscience, via EurekAlert!, a service of AAAS.
Chronic inflammatory diseases like rheumatoid arthritis, inflammatory bowel disease, psoriasis, and liver disease cause "sickness behaviors," including fatigue, malaise, and loss of social interest. However, it has been unclear how inflammation in other organs in the body can impact the brain and behavior.
The researchers found that in mice with inflamed livers, white blood cells called monocytes infiltrated the brain. These findings support previous research demonstrating the presence of immune cells in the brain following organ inflammation, challenging the long-held belief that the blood-brain barrier prevents immune cells from accessing the brain.
"Using an experimental model of liver inflammation, our group has demonstrated for the first time the existence of a novel communication pathway between the inflamed liver and the brain," said the study's senior author Mark Swain, MD, Professor of Medicine at the University of Calgary.
Swain and his colleagues found that liver inflammation triggered brain cells called microglia to produce CCL2, a chemical that attracts monocytes. When the researchers blocked CCL2 signaling, monocytes did not enter the brain despite ongoing inflammation in the liver.
Liver inflammation also stimulated cells in the blood to make an immune chemical (TNFα). When the researchers blocked the signaling of this immune chemical, microglia produced less CCL2, and monocytes stayed out of the brain.
In the mice with inflamed livers, preventing the entry of monocytes into the brain reduced sickness behaviors; mice showed more mobility and social interaction. These findings suggest that people with chronic inflammatory diseases may benefit from treatments that limit monocyte access to the brain.
"Sickness behavior significantly impacts quality of life. Our findings further our understanding and may generate potential new avenues for treatment of these often crippling symptoms," said Swain.
"The brain is the master coordinator of many of our bodies' defense responses, so it must be able to sense injury and inflammation in distant body organs. This study starts to explain the peripheral communication signals that activate the brain," said Nancy Rothwell, PhD, DSc, at the University of Manchester, an expert on brain inflammation who is unaffiliated with the study.
The research was supported by the Canadian Institutes of Health Research, the Canadian Liver Foundation, and the Alberta Heritage Foundation for Medical Research.
Adapted from materials provided by Society for Neuroscience, via EurekAlert!, a service of AAAS.
Doctor fears needle disease outbreak
SOMBA K'E/YELLOWKNIFE - Intravenous crack cocaine, a huge factor in the HIV and hepatitis C outbreaks in Vancouver over the last few decades, is becoming a growing problem in Yellowknife, according to one emergency room doctor.
Dr. David Pontin took a break from his job as an emergency room physician to do an interview about the health problems intravenous crack cocaine poses to our community
Dr. David Pontin, a physician at Stanton Territorial Hospital, said he is beginning to see IV crack-related cases of hepatitis C in the ER.
In a letter addressed to the territorial government, Pontin wrote: "We have a situation here that is akin to kindling waiting for a flame. Our homeless population is highly addicted already and the introduction of IV crack use is the flame that will cause an explosion of HIV and hepatitis C." Crack cocaine in smoking form has given rise to hepatitis C and HIV problems in the past due to unsafe sex practised while on the drug. But melted down and injected, crack cocaine really kicks the spread of these diseases into high gear, he said.
"A hardcore heroin addict might inject twice a day. A hardcore IV crack user might inject twice an hour," said Pontin. "The chances of spreading illnesses like HIV or hepatitis C through dirty syringes explodes."
Dr. Pontin worked for many years at a downtown Vancouver hospital and saw the monumental problem the city faced with drug addiction and communicable disease.
Upon moving here a few years ago, he saw a strikingly similar demographic. The downtown homeless population accounts for the majority of the ER visits to Stanton, he said, and most of those visits stem from drug or alcohol problems.
"It may be an early alarm bell," said Pontin. "But it's an alarm bell nonetheless, and we need to take this very seriously."
He said if nothing is done now, the costs to the public may be high. Not only is the prevalence of communicable disease a huge risk to public health, but if the diseases are improperly treated, problems like multi-drug-resistant HIV arise.
What Vancouver has implemented in order to curb the rocketing rates of syringe-spread disease is a "syringe exchange program," and the highly-controversial and experimental Insite - a supervised facility where drug users can come and ingest their previously acquired substances in the safest manner possible. The cornerstone of an addictions management program, according to Pontin, is having a needle exchange program in place to curb the spread and then talking to the addicts about getting off the drugs with things like detox programs and long-term treatment programs.
"First of all, before all that, it's a cultural kind of change (that needs to take place)," said Pontin.
"We're moving farther and farther away from this idea that addicts are criminals, but if you look at addiction as a health problem - as a chronic health problem - it is the most treatable and curable of all health problems."
The situation is getting dire, and serious action needs to be taken before this problem has a chance to get worse, said Pontin.
Dr. Cindy Orlaw, the NWT's chief medical officer, said she only recently became aware of intravenous needle use in the city but that doesn't mean it's something that should be taken for granted.
"It's a drug you don't experiment with, because if you do crack cocaine once you're addicted forever and you'll never get that high again," said Orlaw, adding that people try crack cocaine intravenously in an attempt to reach a high they used to get by smoking it.
"It does not do that," said Orlaw.
Dr. David Pontin took a break from his job as an emergency room physician to do an interview about the health problems intravenous crack cocaine poses to our community
Dr. David Pontin, a physician at Stanton Territorial Hospital, said he is beginning to see IV crack-related cases of hepatitis C in the ER.
In a letter addressed to the territorial government, Pontin wrote: "We have a situation here that is akin to kindling waiting for a flame. Our homeless population is highly addicted already and the introduction of IV crack use is the flame that will cause an explosion of HIV and hepatitis C." Crack cocaine in smoking form has given rise to hepatitis C and HIV problems in the past due to unsafe sex practised while on the drug. But melted down and injected, crack cocaine really kicks the spread of these diseases into high gear, he said.
"A hardcore heroin addict might inject twice a day. A hardcore IV crack user might inject twice an hour," said Pontin. "The chances of spreading illnesses like HIV or hepatitis C through dirty syringes explodes."
Dr. Pontin worked for many years at a downtown Vancouver hospital and saw the monumental problem the city faced with drug addiction and communicable disease.
Upon moving here a few years ago, he saw a strikingly similar demographic. The downtown homeless population accounts for the majority of the ER visits to Stanton, he said, and most of those visits stem from drug or alcohol problems.
"It may be an early alarm bell," said Pontin. "But it's an alarm bell nonetheless, and we need to take this very seriously."
He said if nothing is done now, the costs to the public may be high. Not only is the prevalence of communicable disease a huge risk to public health, but if the diseases are improperly treated, problems like multi-drug-resistant HIV arise.
What Vancouver has implemented in order to curb the rocketing rates of syringe-spread disease is a "syringe exchange program," and the highly-controversial and experimental Insite - a supervised facility where drug users can come and ingest their previously acquired substances in the safest manner possible. The cornerstone of an addictions management program, according to Pontin, is having a needle exchange program in place to curb the spread and then talking to the addicts about getting off the drugs with things like detox programs and long-term treatment programs.
"First of all, before all that, it's a cultural kind of change (that needs to take place)," said Pontin.
"We're moving farther and farther away from this idea that addicts are criminals, but if you look at addiction as a health problem - as a chronic health problem - it is the most treatable and curable of all health problems."
The situation is getting dire, and serious action needs to be taken before this problem has a chance to get worse, said Pontin.
Dr. Cindy Orlaw, the NWT's chief medical officer, said she only recently became aware of intravenous needle use in the city but that doesn't mean it's something that should be taken for granted.
"It's a drug you don't experiment with, because if you do crack cocaine once you're addicted forever and you'll never get that high again," said Orlaw, adding that people try crack cocaine intravenously in an attempt to reach a high they used to get by smoking it.
"It does not do that," said Orlaw.
Vertex Pharmaceuticals Closes on Acquisition of ViroChem Pharma
Purchase Price $100 Million and 10.7 Million Shares-
-Vertex Acquires Two HCV Polymerase Inhibitors in Deal-
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX), completed its acquisition today of ViroChem Pharma Inc., a privately-held company with two investigational HCV polymerase inhibitors in clinical development. ViroChem shareholders received $100 million in cash and approximately 10.7 million shares of Vertex common stock. The shares issued in this transaction are expected to be available for resale upon filing of the registration statement.
The acquisition advances Vertex’s strategy to pursue novel combinations of Specifically Targeted Antiviral Therapies for hepatitis C (STAT-Cs) in the treatment of HCV infection. Vertex now owns worldwide rights to the ViroChem HCV drug development portfolio, including VCH-222 and VCH-759, which have demonstrated substantial reductions in plasma HCV RNA when dosed as single agents and have been well tolerated in early clinical studies to date. Vertex expects to begin clinical evaluation of novel combination regimens of its HCV protease inhibitor telaprevir, currently in Phase 3 clinical development, in the second half of 2009.
About Vertex
Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company's strategy is to commercialize its products both independently and in collaboration with major pharmaceutical companies. Vertex's product pipeline is focused on viral diseases, cystic fibrosis, inflammation, autoimmune diseases, cancer, and pain. Vertex co-discovered the HIV protease inhibitor, Lexiva, with GlaxoSmithKline.
Lexiva is a registered trademark of the GlaxoSmithKline group of companies.
-Vertex Acquires Two HCV Polymerase Inhibitors in Deal-
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX), completed its acquisition today of ViroChem Pharma Inc., a privately-held company with two investigational HCV polymerase inhibitors in clinical development. ViroChem shareholders received $100 million in cash and approximately 10.7 million shares of Vertex common stock. The shares issued in this transaction are expected to be available for resale upon filing of the registration statement.
The acquisition advances Vertex’s strategy to pursue novel combinations of Specifically Targeted Antiviral Therapies for hepatitis C (STAT-Cs) in the treatment of HCV infection. Vertex now owns worldwide rights to the ViroChem HCV drug development portfolio, including VCH-222 and VCH-759, which have demonstrated substantial reductions in plasma HCV RNA when dosed as single agents and have been well tolerated in early clinical studies to date. Vertex expects to begin clinical evaluation of novel combination regimens of its HCV protease inhibitor telaprevir, currently in Phase 3 clinical development, in the second half of 2009.
About Vertex
Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company's strategy is to commercialize its products both independently and in collaboration with major pharmaceutical companies. Vertex's product pipeline is focused on viral diseases, cystic fibrosis, inflammation, autoimmune diseases, cancer, and pain. Vertex co-discovered the HIV protease inhibitor, Lexiva, with GlaxoSmithKline.
Lexiva is a registered trademark of the GlaxoSmithKline group of companies.
FDA Approves Expanded Indication for Peginterferon-Based Combination Therapy for Chronic HCV
March 12, 2009 — Schering-Plough Corporation announced yesterday that the US Food and Drug Administration (FDA) has approved an expanded indication for peginterferon-based combination therapy for chronic hepatitis C virus (HCV) infection. Peginterferon alfa-2b (PegIntron) and ribavirin, USP (Rebetol) combination therapy is no longer restricted to treatment-naive patients and may be used to treat chronic HCV infection in patients 3 years of age and older with compensated liver disease.
"With the FDA approval of Pegintron and Rebetol combination therapy for this new indication, U.S. physicians now have a treatment option that offers a second chance for success to certain patients who failed prior therapy," Robert J. Spiegel, MD, chief medical officer and senior vice president, Schering-Plough Research Institute, said in a news release.
In the United States, this pegylated interferon combination therapy is now the first and only such therapy available that is not restricted to treatment-naive patients, offering an important therapeutic option for selected patients refractory to previous HCV treatment. The numbers of such patients are increasing and currently exceed 100,000 patients.
Factors associated with lower probability of success from retreatment after failing a course of therapy include previous nonresponse, previous use of pegylated interferon, significant bridging fibrosis or cirrhosis, and infection with HCV genotype 1.
"Based on a patient's treatment history, physicians can identify which patients may be right for retreatment with Pegintron combination therapy and may have the best chance to achieve a sustained response," Eugene R. Schiff, MD, director of the Center for Liver Diseases, University of Miami Miller School of Medicine, Florida, and a lead investigator for the pivotal clinical trial, said in a news release. "Conversely, patients with certain treatment characteristics who are unlikely to respond to this regimen can be advised accordingly."
FDA approval of the expanded indication was based on findings from 1 of the clinical trials in Evaluation of PEG-INTRON in Control of Hepatitis C Cirrhosis study (EPIC3), in which achievement of undetectable HCV RNA at treatment week 12 strongly predicted sustained virologic response (SVR).
"Patients with undetectable virus at week 12 have a better chance for success and can be motivated to continue treatment, and those patients who fail to achieve an early response can have their therapy stopped with confidence, thus avoiding unnecessary treatment and potential adverse events," Dr. Schiff said.
In this noncomparative trial, 2293 adults with moderate to severe fibrosis or cirrhosis who failed previous treatment for at least 12 weeks with combination interferon alfa/ribavirin received peginterferon alfa-2b (1.5 μg/kg once weekly) plus weight-adjusted ribavirin (800 – 1400 mg daily). Prior nonresponders (who had detectable levels of HCV RNA after ≥12 weeks of treatment) and prior relapsers (who did not have detectable levels of HCV RNA at the end of treatment and later relapsed) were included.
Response rate, defined as undetectable HCV RNA at 24 weeks posttreatment, was 22% overall. At treatment week 12, 64% of patients did not achieve undetectable HCV RNA and were offered enrollment into long-term treatment trials. Among patients with undetectable HCV RNA at treatment week 12, those infected with HCV genotype 1 had an SVR rate of 48% vs 70% for those with HCV genotype 2 or 3. For all HCV genotypes, patients with higher fibrosis scores were less likely to achieve SVR.
Regardless of HCV genotype, the recommended treatment duration with peginterferon alfa-2b combination therapy is 48 weeks. Retreated patients with detectable HCV RNA at week 12 or 24 are highly unlikely to achieve SVR, and discontinuing treatment should therefore be considered.
Adverse events associated with peginterferon alfa-2b and ribavirin as retreatment are similar to those reported during clinical trials of treatment-naive patients. Interferon alfa therapy requires close monitoring with periodic clinical and laboratory evaluations, because it may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders.
Ribavirin may cause birth defects and fetal death, so pregnancy must be avoided in female patients and in female partners of male patients. Ribavirin also causes hemolytic anemia and should be considered a potential carcinogen.
"With the FDA approval of Pegintron and Rebetol combination therapy for this new indication, U.S. physicians now have a treatment option that offers a second chance for success to certain patients who failed prior therapy," Robert J. Spiegel, MD, chief medical officer and senior vice president, Schering-Plough Research Institute, said in a news release.
In the United States, this pegylated interferon combination therapy is now the first and only such therapy available that is not restricted to treatment-naive patients, offering an important therapeutic option for selected patients refractory to previous HCV treatment. The numbers of such patients are increasing and currently exceed 100,000 patients.
Factors associated with lower probability of success from retreatment after failing a course of therapy include previous nonresponse, previous use of pegylated interferon, significant bridging fibrosis or cirrhosis, and infection with HCV genotype 1.
"Based on a patient's treatment history, physicians can identify which patients may be right for retreatment with Pegintron combination therapy and may have the best chance to achieve a sustained response," Eugene R. Schiff, MD, director of the Center for Liver Diseases, University of Miami Miller School of Medicine, Florida, and a lead investigator for the pivotal clinical trial, said in a news release. "Conversely, patients with certain treatment characteristics who are unlikely to respond to this regimen can be advised accordingly."
FDA approval of the expanded indication was based on findings from 1 of the clinical trials in Evaluation of PEG-INTRON in Control of Hepatitis C Cirrhosis study (EPIC3), in which achievement of undetectable HCV RNA at treatment week 12 strongly predicted sustained virologic response (SVR).
"Patients with undetectable virus at week 12 have a better chance for success and can be motivated to continue treatment, and those patients who fail to achieve an early response can have their therapy stopped with confidence, thus avoiding unnecessary treatment and potential adverse events," Dr. Schiff said.
In this noncomparative trial, 2293 adults with moderate to severe fibrosis or cirrhosis who failed previous treatment for at least 12 weeks with combination interferon alfa/ribavirin received peginterferon alfa-2b (1.5 μg/kg once weekly) plus weight-adjusted ribavirin (800 – 1400 mg daily). Prior nonresponders (who had detectable levels of HCV RNA after ≥12 weeks of treatment) and prior relapsers (who did not have detectable levels of HCV RNA at the end of treatment and later relapsed) were included.
Response rate, defined as undetectable HCV RNA at 24 weeks posttreatment, was 22% overall. At treatment week 12, 64% of patients did not achieve undetectable HCV RNA and were offered enrollment into long-term treatment trials. Among patients with undetectable HCV RNA at treatment week 12, those infected with HCV genotype 1 had an SVR rate of 48% vs 70% for those with HCV genotype 2 or 3. For all HCV genotypes, patients with higher fibrosis scores were less likely to achieve SVR.
Regardless of HCV genotype, the recommended treatment duration with peginterferon alfa-2b combination therapy is 48 weeks. Retreated patients with detectable HCV RNA at week 12 or 24 are highly unlikely to achieve SVR, and discontinuing treatment should therefore be considered.
Adverse events associated with peginterferon alfa-2b and ribavirin as retreatment are similar to those reported during clinical trials of treatment-naive patients. Interferon alfa therapy requires close monitoring with periodic clinical and laboratory evaluations, because it may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders.
Ribavirin may cause birth defects and fetal death, so pregnancy must be avoided in female patients and in female partners of male patients. Ribavirin also causes hemolytic anemia and should be considered a potential carcinogen.
Hepatitis C increased risk for immune thrombocytopenic purpura
Patients with hepatitis C may be at an increased risk for developing immune thrombocytopenic purpura, according to a study conducted among U.S. veterans. The treatment of hepatitis C with interferon alfa may also increase the risk of ITP as well as autoimmune hemolytic anemia, according to the study’s findings.
Several small single-institution studies have previously linked hepatitis C to the development of autoimmune cytopenias. In this study, researchers examined a large cohort of 120,691 U.S. veterans infected with hepatitis C and compared them with 454,905 matched uninfected veterans. Mean follow-up was 2.5 years.
At the end of follow-up, there were 296 cases of ITP and 90 cases of autoimmune hemolytic anemia. The overall incidence rate of ITP was higher in veterans infected with hepatitis C compared with uninfected veterans (30.2 vs. 18.5 per 100,000 person years). Incidence of autoimmune hemolytic anemia was also higher among infected veterans compared with uninfected veterans (11.4 vs. 5.0 per 100,000 person years).
Infection with hepatitis C was associated with an increased risk for both ITP (HR=1.8; 95% CI, 1.4-2.3) and autoimmune hemolytic anemia (HR=2.8; 95% CI 1.8-2.4).
Researchers found that the development of autoimmune hemolytic anemia was associated with hepatitis C treatment and not the disease itself. Patients treated for hepatitis C had a HR of 11.6 for developing autoimmune hemolytic anemia (95% CI, 7.0-19.3).
However, both hepatitis C (HR=1.7; 95% CI, 1.3-2.2) and treatment for hepatitis C with interferon alfa (HR=2.4; 95% CI 1.5-3.7) were independently associated with an increased risk for ITP. by Leah Lawrence
Arch Intern Med. 2009;169:357-363
Several small single-institution studies have previously linked hepatitis C to the development of autoimmune cytopenias. In this study, researchers examined a large cohort of 120,691 U.S. veterans infected with hepatitis C and compared them with 454,905 matched uninfected veterans. Mean follow-up was 2.5 years.
At the end of follow-up, there were 296 cases of ITP and 90 cases of autoimmune hemolytic anemia. The overall incidence rate of ITP was higher in veterans infected with hepatitis C compared with uninfected veterans (30.2 vs. 18.5 per 100,000 person years). Incidence of autoimmune hemolytic anemia was also higher among infected veterans compared with uninfected veterans (11.4 vs. 5.0 per 100,000 person years).
Infection with hepatitis C was associated with an increased risk for both ITP (HR=1.8; 95% CI, 1.4-2.3) and autoimmune hemolytic anemia (HR=2.8; 95% CI 1.8-2.4).
Researchers found that the development of autoimmune hemolytic anemia was associated with hepatitis C treatment and not the disease itself. Patients treated for hepatitis C had a HR of 11.6 for developing autoimmune hemolytic anemia (95% CI, 7.0-19.3).
However, both hepatitis C (HR=1.7; 95% CI, 1.3-2.2) and treatment for hepatitis C with interferon alfa (HR=2.4; 95% CI 1.5-3.7) were independently associated with an increased risk for ITP. by Leah Lawrence
Arch Intern Med. 2009;169:357-363
Ethnic Differences Found for Fatty Liver Disease and Insulin Resistance
February 28, 2009 — Ethnic differences have been found for nonalcoholic fatty liver disease (NAFLD) and insulin resistance, according to the results of the largest population-based study of this topic to date, reported in the March issue of Hepatology.
"[NAFLD] is a spectrum of disorders defined by abnormal accumulation of triglyceride in liver," write Richard Guerrero, from the University of Texas Southwestern Medical Center at Dallas, and colleagues. "We have previously shown that Hispanics were at greater risk for nonalcoholic fatty liver disease than were African-Americans despite a similar prevalence of risk factors between these groups."
The goal of this study was to assess the contribution of body fat distribution to the differing prevalence of hepatic steatosis in 3 major US ethnic groups: black, Hispanic, and white. Proton magnetic resonance spectroscopy, dual-energy x-ray absorptiometry, and multislice abdominal magnetic resonance imaging were performed in a study cohort of 2170 participants.
Compared with Hispanics and whites, blacks had less intraperitoneal (IP) fat and more lower extremity fat, despite controlling for age and total adiposity. After controlling for total, abdominal subcutaneous, and lower extremity adiposity, these groups still differed in hepatic triglyceride content (HTGC). Controlling for IP fat nearly abolished the differences in HTGC, however, which suggests that IP and liver fat are closely related independent of ethnicity.
Although blacks had lower levels of IP and liver fat, prevalence of insulin resistance in this group was similar to that in Hispanics, in whom levels of IP and liver fat were highest. After controlling for IP fat, blacks had the highest insulin levels and homeostasis model assessment values and the lowest serum triglyceride levels.
"IP fat is linked to HTGC, irrespective of ethnicity," the study authors write. "The differing prevalence of hepatic steatosis between these groups was associated with similar differences in visceral adiposity. The metabolic response to obesity and insulin resistance differs in African-Americans when compared to either Hispanics or Caucasians: African-Americans appear to be more resistant to both the accretion of triglyceride in the abdominal visceral compartment (adipose tissue and liver) and hypertriglyceridemia associated with insulin resistance."
Study limitations include inability to determine whether visceral fat causes the development of hepatic steatosis or is simply a marker of an underlying metabolic derangement contributing to excess liver fat.
"Many of the derangements in lipid metabolism typically associated with insulin resistance were not present in African-Americans," the study authors conclude. "A possible explanation for these findings is that the insulin-resistant phenotype is: (1) a function of the organ contributing primarily to reduced insulin sensitivity and/or (2) a function of the ability to expand subcutaneous adipose tissue in response to overnutrition. Further study is needed to establish the basis for this insulin resistance paradox."
The Donald W. Reynolds Cardiovascular Clinical Research Center at Dallas, supported by the National Institutes of Health grants, supported this study. The study authors have disclosed no relevant financial relationships.
"[NAFLD] is a spectrum of disorders defined by abnormal accumulation of triglyceride in liver," write Richard Guerrero, from the University of Texas Southwestern Medical Center at Dallas, and colleagues. "We have previously shown that Hispanics were at greater risk for nonalcoholic fatty liver disease than were African-Americans despite a similar prevalence of risk factors between these groups."
The goal of this study was to assess the contribution of body fat distribution to the differing prevalence of hepatic steatosis in 3 major US ethnic groups: black, Hispanic, and white. Proton magnetic resonance spectroscopy, dual-energy x-ray absorptiometry, and multislice abdominal magnetic resonance imaging were performed in a study cohort of 2170 participants.
Compared with Hispanics and whites, blacks had less intraperitoneal (IP) fat and more lower extremity fat, despite controlling for age and total adiposity. After controlling for total, abdominal subcutaneous, and lower extremity adiposity, these groups still differed in hepatic triglyceride content (HTGC). Controlling for IP fat nearly abolished the differences in HTGC, however, which suggests that IP and liver fat are closely related independent of ethnicity.
Although blacks had lower levels of IP and liver fat, prevalence of insulin resistance in this group was similar to that in Hispanics, in whom levels of IP and liver fat were highest. After controlling for IP fat, blacks had the highest insulin levels and homeostasis model assessment values and the lowest serum triglyceride levels.
"IP fat is linked to HTGC, irrespective of ethnicity," the study authors write. "The differing prevalence of hepatic steatosis between these groups was associated with similar differences in visceral adiposity. The metabolic response to obesity and insulin resistance differs in African-Americans when compared to either Hispanics or Caucasians: African-Americans appear to be more resistant to both the accretion of triglyceride in the abdominal visceral compartment (adipose tissue and liver) and hypertriglyceridemia associated with insulin resistance."
Study limitations include inability to determine whether visceral fat causes the development of hepatic steatosis or is simply a marker of an underlying metabolic derangement contributing to excess liver fat.
"Many of the derangements in lipid metabolism typically associated with insulin resistance were not present in African-Americans," the study authors conclude. "A possible explanation for these findings is that the insulin-resistant phenotype is: (1) a function of the organ contributing primarily to reduced insulin sensitivity and/or (2) a function of the ability to expand subcutaneous adipose tissue in response to overnutrition. Further study is needed to establish the basis for this insulin resistance paradox."
The Donald W. Reynolds Cardiovascular Clinical Research Center at Dallas, supported by the National Institutes of Health grants, supported this study. The study authors have disclosed no relevant financial relationships.
Scripps Research Team Identifies Key Molecules that Inhibit Viral Production
Discovery May Aid in the Development of Anti-Hepatitis C Virus Drugs
JUPITER, FL, March 9, 2009—A team from The Scripps Research Institute has found a way to inhibit viral production of the Hepatitis C virus (HCV). The advance has the potential to accelerate future research on the virus life cycle and to aid in the development of novel HVC drugs.
The research, led by Professor Donny Strosberg of Scripps Florida, was published on March 4, 2009, in the Journal of General Virology's advance, online edition, Papers in Press.
In the new study, Strosberg and his colleagues describe peptides (molecules of two or more amino acids) derived from the core protein of hepatitis C. The team found that these peptides inhibit not only dimerization of the core protein (the joining of two identical subunits), but also production of the actual virus itself.
"We went for the simplest solution, taking a peptide from core to see if we could block the interaction," Strosberg said, "and it did."
The Problem with Hepatitis C
With over 170 million people infected worldwide by HCV, new therapeutic strategies for HVC—a blood-borne disease that affects the liver—are urgently needed.
But one of the critical problems in developing drugs for HCV is that it mutates at such prodigious rates. An RNA virus like hepatitis C can mutate at a rate estimated as high as one million times that of DNA viruses; in contrast, DNA viruses contain an enzyme (polymerase) that acts as something of a proof reader to ensure that newly transcribed DNA strands are the same as the original, helping to reduce mutations.
"In one sense, the ongoing issue with hepatitis C is that there are still so very few drugs to treat the virus and very few tools to study it," Strosberg said. "We set out to develop new tools and to identify a new target – core, the capsid protein. By targeting the interactions of core with itself or other proteins, we could reduce the problem of rapid mutation not only because the core protein mutates significantly less, but also because mutations that would affect the interface between core and itself or other proteins would often be more likely to deactivate the virus, in contrast to mutations in viral enzymes which often lead to increased resistance to drugs."
Recent efforts to develop therapeutic strategies against HCV have concentrated on designing inhibitors that target several of the 10 HCV proteins that comprise the virus, including mostly the non-structural proteins. However, as the study points out, the one HCV structural protein that has not been targeted yet is the core protein, the one responsible for assembly and packaging of the HCV RNA genome.
The Core of the Matter
Core, the most conserved protein among all HCV genotypes, plays several essential roles in the viral cycle in the host cell; studies have suggested that these core-core or core-other protein interactions can modulate various functions including signaling, apoptosis or programmed cell death, lipid metabolism, and gene transcription.
The core protein is particularly important in the assembly of the hepatitis C nucleocapsid, an essential step in the formation of infectious viral particles; the nucleocapsid is the viral genome protected by a protein coat—the capsid. This core protein plays an essential role in the HCV cycle during assembly and release of the infectious virus, as well as disassembly of viral particles upon entering host cells.
Looking closely at the core interaction with itself, Strosberg developed several novel quantitative assays or tests for monitoring these protein-protein interactions with the specific goal of identifying inhibitors of the core dimerization, which would block virus production.
"People have been dreaming about inhibiting protein-protein interactions, as a new El Dorado for finding novel drug targets," says Strosberg, "but few conclusive studies have emerged, except in the virus-host area."
Inhibition of HCV Production
The new research, however, led to the discovery of two peptides that inhibited HCV production by 68 percent and 63 percent, respectively; a third related peptide showed 50 percent inhibition. When added to HCV-infected cells, each of the three peptides blocked release but not replication of infectious virus; viral RNA levels were reduced by seven fold. Strosberg notes that the efficacy of small molecules like these can often be improved over initial levels.
"After we'd finished our work, we learned that Frank Chisari—one of the leading experts on HCV who works at Scripps Research in La Jolla—had been looking at similar peptides using a very different approach," said Strosberg. "One of his peptides was the same as ours—it also inhibited virus production. It's an incredible coincidence and a confirmation of our study."
The first author of the study, "Peptide Inhibitors of Hepatitis C Core Oligomerization and Virus Production," is Smitha Kota, a member of the Strosberg laboratory at The Scripps Research Institute's Florida campus. Others authors include Carlos Coito, and Guillaume Mousseau of The Scripps Research Institute and J-P Lavergne of the Institut de Biologie et Chimie des Protéines of the CNRS at the University of Lyon, France.
JUPITER, FL, March 9, 2009—A team from The Scripps Research Institute has found a way to inhibit viral production of the Hepatitis C virus (HCV). The advance has the potential to accelerate future research on the virus life cycle and to aid in the development of novel HVC drugs.
The research, led by Professor Donny Strosberg of Scripps Florida, was published on March 4, 2009, in the Journal of General Virology's advance, online edition, Papers in Press.
In the new study, Strosberg and his colleagues describe peptides (molecules of two or more amino acids) derived from the core protein of hepatitis C. The team found that these peptides inhibit not only dimerization of the core protein (the joining of two identical subunits), but also production of the actual virus itself.
"We went for the simplest solution, taking a peptide from core to see if we could block the interaction," Strosberg said, "and it did."
The Problem with Hepatitis C
With over 170 million people infected worldwide by HCV, new therapeutic strategies for HVC—a blood-borne disease that affects the liver—are urgently needed.
But one of the critical problems in developing drugs for HCV is that it mutates at such prodigious rates. An RNA virus like hepatitis C can mutate at a rate estimated as high as one million times that of DNA viruses; in contrast, DNA viruses contain an enzyme (polymerase) that acts as something of a proof reader to ensure that newly transcribed DNA strands are the same as the original, helping to reduce mutations.
"In one sense, the ongoing issue with hepatitis C is that there are still so very few drugs to treat the virus and very few tools to study it," Strosberg said. "We set out to develop new tools and to identify a new target – core, the capsid protein. By targeting the interactions of core with itself or other proteins, we could reduce the problem of rapid mutation not only because the core protein mutates significantly less, but also because mutations that would affect the interface between core and itself or other proteins would often be more likely to deactivate the virus, in contrast to mutations in viral enzymes which often lead to increased resistance to drugs."
Recent efforts to develop therapeutic strategies against HCV have concentrated on designing inhibitors that target several of the 10 HCV proteins that comprise the virus, including mostly the non-structural proteins. However, as the study points out, the one HCV structural protein that has not been targeted yet is the core protein, the one responsible for assembly and packaging of the HCV RNA genome.
The Core of the Matter
Core, the most conserved protein among all HCV genotypes, plays several essential roles in the viral cycle in the host cell; studies have suggested that these core-core or core-other protein interactions can modulate various functions including signaling, apoptosis or programmed cell death, lipid metabolism, and gene transcription.
The core protein is particularly important in the assembly of the hepatitis C nucleocapsid, an essential step in the formation of infectious viral particles; the nucleocapsid is the viral genome protected by a protein coat—the capsid. This core protein plays an essential role in the HCV cycle during assembly and release of the infectious virus, as well as disassembly of viral particles upon entering host cells.
Looking closely at the core interaction with itself, Strosberg developed several novel quantitative assays or tests for monitoring these protein-protein interactions with the specific goal of identifying inhibitors of the core dimerization, which would block virus production.
"People have been dreaming about inhibiting protein-protein interactions, as a new El Dorado for finding novel drug targets," says Strosberg, "but few conclusive studies have emerged, except in the virus-host area."
Inhibition of HCV Production
The new research, however, led to the discovery of two peptides that inhibited HCV production by 68 percent and 63 percent, respectively; a third related peptide showed 50 percent inhibition. When added to HCV-infected cells, each of the three peptides blocked release but not replication of infectious virus; viral RNA levels were reduced by seven fold. Strosberg notes that the efficacy of small molecules like these can often be improved over initial levels.
"After we'd finished our work, we learned that Frank Chisari—one of the leading experts on HCV who works at Scripps Research in La Jolla—had been looking at similar peptides using a very different approach," said Strosberg. "One of his peptides was the same as ours—it also inhibited virus production. It's an incredible coincidence and a confirmation of our study."
The first author of the study, "Peptide Inhibitors of Hepatitis C Core Oligomerization and Virus Production," is Smitha Kota, a member of the Strosberg laboratory at The Scripps Research Institute's Florida campus. Others authors include Carlos Coito, and Guillaume Mousseau of The Scripps Research Institute and J-P Lavergne of the Institut de Biologie et Chimie des Protéines of the CNRS at the University of Lyon, France.
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