Human Genome Sciences' Albuferon has demonstrated non-inferiority to the current standard of care in a Phase III trial in treatment-naive genotype 1 hepatitis C patients. Although Albuferon's less frequent dosing schedule is an advantage, the fact that it did not show superior efficacy in this area of high unmet need suggests that the drug is unlikely to threaten existing interferon therapies.
Albuferon meets non-inferiority endpoint but fails to offer major benefits over existing treatments.
Human Genome Sciences (HGS) has announced results from Phase III trials for its investigational interferon therapy for the treatment of hepatitis C infection. Albinterferon alfa-2b (Albuferon) is a long-acting, injectable interferon therapy given once every two weeks which is being developed by HGS and Novartis.
The ACHIEVE 1 study investigated Albuferon and ribavirin in 1,278 treatment-naive patients with chronic hepatitis C genotype 1 for 48 weeks. The primary endpoint was the sustained virological response (SVR) rate, 24 weeks after the end of treatment. Top line results demonstrate that Albuferon met its primary efficacy endpoint of non-inferiority to peginterferon alfa-2a (Roche's market leading Pegasys), with 48.2% of patients achieving SVR in the 900-mcg Albuferon arm, versus 51% in the Pegasys treatment group in an intention-to-treat analysis. Importantly, the rate of Albuferon treatment discontinuations due to adverse events was more than double that of Pegasys, at 10.4% versus 4.1%. Adverse events observed were those typically associated with interferon therapy.
The standard of care in hepatitis C virus (HCV) therapy currently comprises pegylated interferon alpha in combination with ribavirin. There are two pegylated interferon therapies available, Schering Plough's PegIntron and Roche's Pegasys. Despite the ability of current HCV therapies to cure the infection in some patients, there remains significant room for improvement. Limited efficacy in patients infected with genotype 1 HCV is the greatest unmet need for this class; other drawbacks include high incidence of adverse events, long duration of treatment and consequently suboptimal patient compliance.
Although Albuferon has demonstrated efficacy in genotype 1 patients, the number achieving SVR in ACHIEVE 1 was similar to the current standard of care. Since the drug did numerically, albeit not statistically, slightly worse than Pegasys in genotype 1 patients, it does not address this unmet need any better than its marketed competitors. Moreover, the higher rate of discontinuations in the Albuferon arm indicates that it does not offer any benefits in terms of tolerability either.
Consequently, Datamonitor believes that while Albuferon reduces the dosing frequency, the lack of efficacy compliance benefits in genotype 1 patients makes it unlikely to threaten currently marketed interferon therapies. Therefore, Datamonitor forecasts annual peak sales of just over $200 million in the seven major markets by 2017.
Saturday, March 21, 2009
FDA issues warning on sharing insulin pens and cartridges
The U.S. Food and Drug Administration has issued an alert to health care professionals reminding them that single-patient insulin pens and insulin cartridges should not be used to administer medication to multiple patients due to the potential risk of transmitting blood-borne pathogens such as HIV and the hepatitis viruses.
Insulin pens are pen-shaped injector devices that contain a disposable needle and either an insulin reservoir or an insulin cartridge. The devices typically contain enough insulin for a patient to self-administer several doses of insulin before the reservoir or cartridge is empty. All insulin pens are approved only for single-patient use (one device for only one patient).
The FDA is aware of incidents at two undisclosed hospitals involving more than 2,000 people in which the cartridge component of the insulin pens were used to administer insulin to multiple patients, although the disposable needles were reportedly changed among patients.
"Insulin pens are designed to be safe for one patient to use one pen multiple times with a new, fresh needle for each injection," said Amy Egan, M.D., deputy director of safety at the FDA's Division of Metabolism and Endocrinology Products in the Center for Drug Evaluation and Research. "Insulin pens are not designed, and are not safe, for one pen to be used by more than one patient, even if needles are changed between patients due to the risk of transmitting blood-borne pathogens."
Patients exposed to shared insulin pens are being contacted by the two hospitals and are being offered testing for hepatitis and HIV. Some of the potentially exposed patients have reportedly tested positive for the hepatitis C virus, although it is not known if the virus was spread as a result of insulin pen sharing.
The FDA is working with the Centers for Disease Control and Prevention and professional organizations to address infection control issues related to insulin pens.
Insulin pens are pen-shaped injector devices that contain a disposable needle and either an insulin reservoir or an insulin cartridge. The devices typically contain enough insulin for a patient to self-administer several doses of insulin before the reservoir or cartridge is empty. All insulin pens are approved only for single-patient use (one device for only one patient).
The FDA is aware of incidents at two undisclosed hospitals involving more than 2,000 people in which the cartridge component of the insulin pens were used to administer insulin to multiple patients, although the disposable needles were reportedly changed among patients.
"Insulin pens are designed to be safe for one patient to use one pen multiple times with a new, fresh needle for each injection," said Amy Egan, M.D., deputy director of safety at the FDA's Division of Metabolism and Endocrinology Products in the Center for Drug Evaluation and Research. "Insulin pens are not designed, and are not safe, for one pen to be used by more than one patient, even if needles are changed between patients due to the risk of transmitting blood-borne pathogens."
Patients exposed to shared insulin pens are being contacted by the two hospitals and are being offered testing for hepatitis and HIV. Some of the potentially exposed patients have reportedly tested positive for the hepatitis C virus, although it is not known if the virus was spread as a result of insulin pen sharing.
The FDA is working with the Centers for Disease Control and Prevention and professional organizations to address infection control issues related to insulin pens.
Sustained Viral Response Indicates HCV Infection Cure
NEW YORK (Reuters Health) Mar 19 - A 4-year follow-up of patients with chronic hepatitis C virus (HCV) infection who achieve a sustained viral response (SVR) to interferon-alpha-2b "strongly suggests" that they are "cured," French investigators report in the April issue of Liver International.
Dr. Sarah Maylin and colleagues at Hopital Beaujon in Clichy, France, followed 157 patients with chronic HCV infection who achieved SVR after treatment with interferon-alpha-2b and a control group of 23 patients with detectable HCV RNA and normal serum alanine levels. HCV viral titers and HCV antibodies were measured periodically during 4 years of follow-up.
Serum HCV RNA levels remained undetectable in all patients and HCV antibody titers remained unchanged throughout follow-up.
"This long-term study...demonstrated that SVR...is durable, and HCV antibodies were markedly decreased (mainly those directed against the non-structural proteins), emphasizing an absence of ongoing infection," Dr. Maylin and colleagues write.
"These results strongly suggest that HCV infection (is) cured in patients who achieve an SVR," the researchers say.
The findings show that the humoral immune response to non-structural HCV proteins is short-lived and might be a marker of infected cells," the French investigators say. "A decrease in the antibodies against the (nonstructural) proteins, observed in our study, could reflect a decrease in infected cells, suggesting that there is no antigenic stimulation after viral eradication."
Liver Int 2009;29:511-517.
Dr. Sarah Maylin and colleagues at Hopital Beaujon in Clichy, France, followed 157 patients with chronic HCV infection who achieved SVR after treatment with interferon-alpha-2b and a control group of 23 patients with detectable HCV RNA and normal serum alanine levels. HCV viral titers and HCV antibodies were measured periodically during 4 years of follow-up.
Serum HCV RNA levels remained undetectable in all patients and HCV antibody titers remained unchanged throughout follow-up.
"This long-term study...demonstrated that SVR...is durable, and HCV antibodies were markedly decreased (mainly those directed against the non-structural proteins), emphasizing an absence of ongoing infection," Dr. Maylin and colleagues write.
"These results strongly suggest that HCV infection (is) cured in patients who achieve an SVR," the researchers say.
The findings show that the humoral immune response to non-structural HCV proteins is short-lived and might be a marker of infected cells," the French investigators say. "A decrease in the antibodies against the (nonstructural) proteins, observed in our study, could reflect a decrease in infected cells, suggesting that there is no antigenic stimulation after viral eradication."
Liver Int 2009;29:511-517.
Progress Reported Against Gene Involved in Hepatitis C
Finding could lead to new treatments for the disease, researchers say
WEDNESDAY, March 18 (HealthDay News) -- Nearly 100 genes that support replication of the hepatitis C virus (HCV) in the human body have been identified by Massachusetts General Hospital researchers.
They also found that blocking several of the genes suppressed replication of the virus.
"We may be a few years away from developing therapies based on these findings, but this study is a proof of principle that targeting host factors is a viable therapeutic strategy," Dr. Andrew Tai, of the hospital's gastrointestinal unit and lead researcher on the study, said in a hospital news release.
Long-term HCV infection can lead to liver failure or liver cancer. Currently, a six- to 11-month regimen of peginterferon and the antiviral drug ribavirin is used to treat HCV, but the therapy can cause serious side effects and is ineffective in many people.
Tai and his colleagues examined whether using small interfering RNAs (siRNAs) to block each of the approximately 21,000 predicted messenger RNA transcripts in the human genome had any effect on HCV replication. The siRNA scan identified 96 genes that appear to play a role in HCV replication, and the researchers took a closer look at several of those genes.
One of the genes encodes for an enzyme called PI4KA, believed to play a role in the formation of membrane structures within the cell that may be the site of HCV replication. Another group of genes contributes to formation of the COPI coat that covers several types of cellular vesicles and plays a role in the replication of poliovirus, the researchers said.
They also zeroed in on the gene for a liver protein (hepcidin) that regulates iron absorption. People with chronic HCV infection experience elevated iron levels in the liver and blood.
Blocking each of these genes prevented HCV replication, as did drugs that inhibit PI4KA and COPI.
Further research is needed to identify the molecular mechanisms in these genes that support HCV replication. That could lead to new treatments for HCV infection, the researchers said.
The study is in the March 19 issue of Cell Host & Microbe.
WEDNESDAY, March 18 (HealthDay News) -- Nearly 100 genes that support replication of the hepatitis C virus (HCV) in the human body have been identified by Massachusetts General Hospital researchers.
They also found that blocking several of the genes suppressed replication of the virus.
"We may be a few years away from developing therapies based on these findings, but this study is a proof of principle that targeting host factors is a viable therapeutic strategy," Dr. Andrew Tai, of the hospital's gastrointestinal unit and lead researcher on the study, said in a hospital news release.
Long-term HCV infection can lead to liver failure or liver cancer. Currently, a six- to 11-month regimen of peginterferon and the antiviral drug ribavirin is used to treat HCV, but the therapy can cause serious side effects and is ineffective in many people.
Tai and his colleagues examined whether using small interfering RNAs (siRNAs) to block each of the approximately 21,000 predicted messenger RNA transcripts in the human genome had any effect on HCV replication. The siRNA scan identified 96 genes that appear to play a role in HCV replication, and the researchers took a closer look at several of those genes.
One of the genes encodes for an enzyme called PI4KA, believed to play a role in the formation of membrane structures within the cell that may be the site of HCV replication. Another group of genes contributes to formation of the COPI coat that covers several types of cellular vesicles and plays a role in the replication of poliovirus, the researchers said.
They also zeroed in on the gene for a liver protein (hepcidin) that regulates iron absorption. People with chronic HCV infection experience elevated iron levels in the liver and blood.
Blocking each of these genes prevented HCV replication, as did drugs that inhibit PI4KA and COPI.
Further research is needed to identify the molecular mechanisms in these genes that support HCV replication. That could lead to new treatments for HCV infection, the researchers said.
The study is in the March 19 issue of Cell Host & Microbe.
Hepatitis B Testing Urged for Non-Hodgkin's Lymphoma Treatment: Presented at NCCN
HOLLYWOOD, Fla -- March 16, 2009 -- Before initiating treatment for non-Hodgkin's lymphoma, doctors need to determine if the patient has been infected with hepatitis B virus, especially if treatment will be with rituximab-based therapy, according to a presentation here at the National Comprehensive Cancer Network (NCCN) 14th Annual Conference: Clinical Practice Guidelines & Quality Cancer Care.
"Hepatitis B virus can reactivate with immunosuppression," explained presenter Andrew Zelenetz, MD, PhD, Lymphoma Service, Memorial-Sloan Kettering Cancer Center, New York, New York.
Rituximab depletes B cells in patients with B-cell lymphoma, possibly compromising the immune system and allowing the virus to emerge and reactivate, Dr. Zelenetz said in a presentation on March 13.
If patients are found to be positive for the hepatitis B virus -- as determined by hepatitis B surface antigen, core antibody, e-antigen, and/or viral load -- then the treating physician should consult with a hepatologist, he advised. "This is important because more than 5% of patients with acute hepatitis B virus reactivation will die of liver failure," Dr. Zelenetz said.
The US Food and Drug Administration mandated a black box warning regarding rituximab therapy after cases of fulminant hepatitis were reported. The risk of reactivation persists for as long as 6 months following treatment.
The lymphoma algorithm is designed to guide treatment practice among the 21 institutions that make up the NCCN, including Memorial-Sloan Kettering, which releases treatment guidelines that have become standard-of-care for many institutions worldwide.
Dr. Zelenetz said that hepatitis B testing was added to the guidelines as part of the essential work-up for patients.
Other constituents of that work-up include a physical examination with attention to node-bearing areas, including Waldeyer's ring, and with attention to the size of the liver and spleen; the patient's performance status; a chest-abdominal-pelvic computer-assisted tomography (CT) scan; bone marrow and aspirate test to document clinical stage; and pregnancy testing in women of childbearing age if chemotherapy is considered.
"Positron emission tomography [PET] is not an essential part of the work-up," he said, "although PET has been useful in some cases." Also useful in selected cases are hepatitis C testing, discussion of fertility issues and sperm banking, PET-computed tomography scans, neck CT scans, and echocardiogram.
Dr. Zelenetz said the risk of reactivation is higher among young men, in patients with higher hepatitis B virus DNA before treatment, and in patients with prolonged or deep immunosuppression.
[Presentation title: NCCN Non-Hodgkin's Lymphoma Guidelines Update.]
"Hepatitis B virus can reactivate with immunosuppression," explained presenter Andrew Zelenetz, MD, PhD, Lymphoma Service, Memorial-Sloan Kettering Cancer Center, New York, New York.
Rituximab depletes B cells in patients with B-cell lymphoma, possibly compromising the immune system and allowing the virus to emerge and reactivate, Dr. Zelenetz said in a presentation on March 13.
If patients are found to be positive for the hepatitis B virus -- as determined by hepatitis B surface antigen, core antibody, e-antigen, and/or viral load -- then the treating physician should consult with a hepatologist, he advised. "This is important because more than 5% of patients with acute hepatitis B virus reactivation will die of liver failure," Dr. Zelenetz said.
The US Food and Drug Administration mandated a black box warning regarding rituximab therapy after cases of fulminant hepatitis were reported. The risk of reactivation persists for as long as 6 months following treatment.
The lymphoma algorithm is designed to guide treatment practice among the 21 institutions that make up the NCCN, including Memorial-Sloan Kettering, which releases treatment guidelines that have become standard-of-care for many institutions worldwide.
Dr. Zelenetz said that hepatitis B testing was added to the guidelines as part of the essential work-up for patients.
Other constituents of that work-up include a physical examination with attention to node-bearing areas, including Waldeyer's ring, and with attention to the size of the liver and spleen; the patient's performance status; a chest-abdominal-pelvic computer-assisted tomography (CT) scan; bone marrow and aspirate test to document clinical stage; and pregnancy testing in women of childbearing age if chemotherapy is considered.
"Positron emission tomography [PET] is not an essential part of the work-up," he said, "although PET has been useful in some cases." Also useful in selected cases are hepatitis C testing, discussion of fertility issues and sperm banking, PET-computed tomography scans, neck CT scans, and echocardiogram.
Dr. Zelenetz said the risk of reactivation is higher among young men, in patients with higher hepatitis B virus DNA before treatment, and in patients with prolonged or deep immunosuppression.
[Presentation title: NCCN Non-Hodgkin's Lymphoma Guidelines Update.]
Digestive and liver diseases: no joking matter
Maintaining a healthy digestive system is vital to your health and comfort.
But many people ignore the signs of digestive illness and fail to seek relief from their discomfort because they are embarrassed to discuss the symptoms or their own health histories.
Your digestive system is a series of hollow organs joined in a long, twisting tube. It includes the esophagus, stomach and large and small intestines. Your liver, gallbladder and pancreas contribute to the process of breaking down the foods you eat to build and nourish cells and provide energy.
Among the young and healthy, the digestive tract is a remarkably tolerant system, even when challenged with the most reckless diets and lifestyles. But after the age of 40, and especially as you reach age 50, time begins to take its toll and gastrointestinal problems become more common.
Effectively addressing most digestive issues require conversations about topics that many are embarrassed to discuss, including bowel habits, abdominal pain, stool and flatulence. In general, you should see your doctor if you have:
• Blood in your stool.
• Changes in bowel habits.
• Severe abdominal pain.
• Unintentional weight loss.
• Heartburn not relieved by antacids.
Another digestive disease, hepatitis C, requires discussions about potentially embarrassing aspects of a patient's personal history, including drug use and sexual activity.
Hepatitis C is a serious condition that damages the liver and can lead to potentially fatal liver diseases such as cirrhosis, liver failure and liver cancer. Unlike other common strains, such as hepatitis A and hepatitis B, there is no vaccine to prevent hepatitis C. One of the most common reasons for liver transplants is damage caused by hepatitis C infection. More than four million Americans have been infected with hepatitis C, which is responsible for more than 8,000 deaths each year.
Most people with hepatitis C have no symptoms of the disease. This is why it may persist for years or even decades before it is discovered. In most cases, early diagnosis of hepatitis C depends on the patient's ability to candidly discuss past lifestyle choices.
You can get hepatitis C if your blood comes into contact with blood from someone who already has the virus. The most common cause of transmission is the sharing of needles and other equipment used to inject illegal drugs. The leading risk factors include:
• Past intravenous drug use.
• Tattoos and body piercing using shared needles.
• Past cocaine use.
• High-risk, unprotected sexual activity.
Before 1989 there was a risk of getting hepatitis C from blood transfusions. Now all donated blood is tested for hepatitis C so there is almost no risk of getting the disease from blood transfusions.
Hepatitis C is most often diagnosed by a blood test. However, blood tests conducted in routine physicals do not include tests for hepatitis C. This is why most people with hepatitis C don't know they have the disease, especially since there may be no symptoms.
Some people discover that they have hepatitis C when they donate blood, because all donated blood is tested for hepatitis C virus. Others learn they have hepatitis C when they undergo blood tests for other medical problems. When blood tests show abnormal liver enzymes, a sign of liver damage, additional tests are conducted to find the cause.
It is during these tests that your physician may delve into potentially embarrassing aspects of your lifestyle. It is important to remember that these conversations are completely private. Your doctor is not sitting in judgment. He or she is merely trying to gather information to more effectively care for you.
If you have hepatitis C, the goal of treatment is to get rid of the virus in your body. In fact, hepatitis C is one of the only viruses that can be cured with medication therapies. The most effective cure for hepatitis C requires patients to take antiviral medications for six months to one year.
The digestive system is the source of countless jokes and embarrassment for some. One of the hardest-working, most complex parts of the body is also the subject of misunderstandings, folklore and old wives tales.
In many cases, the first step to getting relief and treating potential digestive diseases is overcoming embarrassing aspects of the symptoms or your own personal history, ignoring those myths and engaging in frank discussions with your physician.
Jeffrey Goldman, MD, is a gastroenterologist at St.JamesHospital and HealthCenters in Olympia Fields. St. James is a member of the Southland Health Alliance.
But many people ignore the signs of digestive illness and fail to seek relief from their discomfort because they are embarrassed to discuss the symptoms or their own health histories.
Your digestive system is a series of hollow organs joined in a long, twisting tube. It includes the esophagus, stomach and large and small intestines. Your liver, gallbladder and pancreas contribute to the process of breaking down the foods you eat to build and nourish cells and provide energy.
Among the young and healthy, the digestive tract is a remarkably tolerant system, even when challenged with the most reckless diets and lifestyles. But after the age of 40, and especially as you reach age 50, time begins to take its toll and gastrointestinal problems become more common.
Effectively addressing most digestive issues require conversations about topics that many are embarrassed to discuss, including bowel habits, abdominal pain, stool and flatulence. In general, you should see your doctor if you have:
• Blood in your stool.
• Changes in bowel habits.
• Severe abdominal pain.
• Unintentional weight loss.
• Heartburn not relieved by antacids.
Another digestive disease, hepatitis C, requires discussions about potentially embarrassing aspects of a patient's personal history, including drug use and sexual activity.
Hepatitis C is a serious condition that damages the liver and can lead to potentially fatal liver diseases such as cirrhosis, liver failure and liver cancer. Unlike other common strains, such as hepatitis A and hepatitis B, there is no vaccine to prevent hepatitis C. One of the most common reasons for liver transplants is damage caused by hepatitis C infection. More than four million Americans have been infected with hepatitis C, which is responsible for more than 8,000 deaths each year.
Most people with hepatitis C have no symptoms of the disease. This is why it may persist for years or even decades before it is discovered. In most cases, early diagnosis of hepatitis C depends on the patient's ability to candidly discuss past lifestyle choices.
You can get hepatitis C if your blood comes into contact with blood from someone who already has the virus. The most common cause of transmission is the sharing of needles and other equipment used to inject illegal drugs. The leading risk factors include:
• Past intravenous drug use.
• Tattoos and body piercing using shared needles.
• Past cocaine use.
• High-risk, unprotected sexual activity.
Before 1989 there was a risk of getting hepatitis C from blood transfusions. Now all donated blood is tested for hepatitis C so there is almost no risk of getting the disease from blood transfusions.
Hepatitis C is most often diagnosed by a blood test. However, blood tests conducted in routine physicals do not include tests for hepatitis C. This is why most people with hepatitis C don't know they have the disease, especially since there may be no symptoms.
Some people discover that they have hepatitis C when they donate blood, because all donated blood is tested for hepatitis C virus. Others learn they have hepatitis C when they undergo blood tests for other medical problems. When blood tests show abnormal liver enzymes, a sign of liver damage, additional tests are conducted to find the cause.
It is during these tests that your physician may delve into potentially embarrassing aspects of your lifestyle. It is important to remember that these conversations are completely private. Your doctor is not sitting in judgment. He or she is merely trying to gather information to more effectively care for you.
If you have hepatitis C, the goal of treatment is to get rid of the virus in your body. In fact, hepatitis C is one of the only viruses that can be cured with medication therapies. The most effective cure for hepatitis C requires patients to take antiviral medications for six months to one year.
The digestive system is the source of countless jokes and embarrassment for some. One of the hardest-working, most complex parts of the body is also the subject of misunderstandings, folklore and old wives tales.
In many cases, the first step to getting relief and treating potential digestive diseases is overcoming embarrassing aspects of the symptoms or your own personal history, ignoring those myths and engaging in frank discussions with your physician.
Jeffrey Goldman, MD, is a gastroenterologist at St.JamesHospital and HealthCenters in Olympia Fields. St. James is a member of the Southland Health Alliance.
Telbivudine Better Than Lamivudine for Chronic Hepatitis B
NEW YORK (Reuters Health) Mar 17 - As a treatment for chronic hepatitis B, telbivudine produces a better therapeutic response than does lamivudine in both HBeAg-positive and -negative patients, according to 2-year follow-up data from the GLOBE trial.
When it became available in 1998, lamivudine revolutionized the treatment of chronic hepatitis B, note Dr. Yun-Fan Liaw, from Chang Gung University College of Medicine, Taipei, Taiwan, and colleagues. The current findings, however, suggest that the newer agent telbivudine has now displaced lamivudine as the treatment of choice.
The GLOBE trial included 921 HBeAg-positive and 446 HBeAg-negative patients who were randomized to receive telbivudine or lamivudine once daily for 104 weeks. Therapeutic response, the main outcome, was defined as a hepatitis B virus DNA level < 5 log10 copies/mL and HBeAg loss or normalization of the alanine aminotransferase level.
In HBeAg-positive patients, the treatment response rate was higher with telbivudine than with lamivudine: 63% vs. 48% (p < 0.001), according to the report in the February issue of Gastroenterology. In HBeAg-negative patients, the corresponding rates were 78% and 66% (p = 0.007).
Compared with lamivudine, treatment with telbivudine in the HBeAg-positive group was associated with higher rates of nondetectable viremia and HBeAg loss and with lower rates of viral resistance. In the HBeAg-negative group, telbivudine use also increased the odds of nondetectable viremia and was tied to less viral resistance.
In general, the two drugs had comparable side effect profiles, although telbivudine was more often linked to grade 3/4 increases in creatine kinase levels: 12.9% vs. 4.1% (p < 0.001).
Despite these findings, however, the future of telbivudine as a long-term treatment for chronic hepatitis B is uncertain, Dr. Robert J. Fontana, from the University of Michigan Medical Center, Ann Arbor, comments in a related editorial.
"The rising incidence of telbivudine-resistant hepatitis B virus will likely limit its long-term utility in the management of chronic hepatitis B virus," he writes. "Additional drugs that target other steps in the hepatitis B virus replication cycle or host immune response are needed."
Gastroenterology 2009;136:389-403,486-495.
When it became available in 1998, lamivudine revolutionized the treatment of chronic hepatitis B, note Dr. Yun-Fan Liaw, from Chang Gung University College of Medicine, Taipei, Taiwan, and colleagues. The current findings, however, suggest that the newer agent telbivudine has now displaced lamivudine as the treatment of choice.
The GLOBE trial included 921 HBeAg-positive and 446 HBeAg-negative patients who were randomized to receive telbivudine or lamivudine once daily for 104 weeks. Therapeutic response, the main outcome, was defined as a hepatitis B virus DNA level < 5 log10 copies/mL and HBeAg loss or normalization of the alanine aminotransferase level.
In HBeAg-positive patients, the treatment response rate was higher with telbivudine than with lamivudine: 63% vs. 48% (p < 0.001), according to the report in the February issue of Gastroenterology. In HBeAg-negative patients, the corresponding rates were 78% and 66% (p = 0.007).
Compared with lamivudine, treatment with telbivudine in the HBeAg-positive group was associated with higher rates of nondetectable viremia and HBeAg loss and with lower rates of viral resistance. In the HBeAg-negative group, telbivudine use also increased the odds of nondetectable viremia and was tied to less viral resistance.
In general, the two drugs had comparable side effect profiles, although telbivudine was more often linked to grade 3/4 increases in creatine kinase levels: 12.9% vs. 4.1% (p < 0.001).
Despite these findings, however, the future of telbivudine as a long-term treatment for chronic hepatitis B is uncertain, Dr. Robert J. Fontana, from the University of Michigan Medical Center, Ann Arbor, comments in a related editorial.
"The rising incidence of telbivudine-resistant hepatitis B virus will likely limit its long-term utility in the management of chronic hepatitis B virus," he writes. "Additional drugs that target other steps in the hepatitis B virus replication cycle or host immune response are needed."
Gastroenterology 2009;136:389-403,486-495.
Protect your child’s liver: Positive Parenting
Your child may have already been given the hepatitis B vaccine, but have you given thought to the other hepatitis diseases that may also harm him? Find out more on what you can do to protect your child.
THE liver is a vital organ in your body. It helps to process nutrients, remove toxins, fight off infections, store energy, and stop bleeding. To allow your liver to keep performing well, you need to protect your liver from various diseases, which can cause liver damage. One of the diseases that may harm your liver is hepatitis.
Hepatitis is an inflammation of the liver, most commonly caused by a viral infection. The five main hepatitis viruses are A, B, C, D, E and G.
Hepatitis A, B and C are the most common types of hepatitis diseases. They vary in terms of severity, means of spread, epidemic features, and preventive measures. Hepatitis can cause the liver to swell and lose its ability to function. It can also lead to cirrhosis (scarring), liver failure or cancer of the liver.
As a parent, you definitely want to keep your child healthy and protect him from this dreaded group of diseases. The good news is, vaccines are currently available for the prevention of hepatitis A and B.
Prevent hepatitis A
Hepatitis A is a disease which goes away within a few weeks. It rarely leads to permanent liver damage in healthy people. The hepatitis A virus is found in stools of the infected person. People most commonly get infected when they consume food or drinks that are contaminated with the infected person’s stool. Lightly cooked seafood like cockles contaminated by faeces or sewage provides a suitable medium to spread hepatitis A.
There is a chance of an outbreak in day-care centres because many young children wear diapers. If an infected child’s stool gets on their hands, they may contaminate the things they touch and transmit the virus to other children who touch these contaminated surfaces. Caregivers may also infect others if they do not wash their hands thoroughly after changing a child’s diaper.
Hepatitis can also spread through infected food handlers, consumption of undercooked oysters, clams, or mussels from contaminated waters, traveling to countries with poor sanitation, and injecting-drug users.
The risk of developing symptoms among people infected with hepatitis A is correlated with age. In children below 6 years of age, there are usually no symptoms. Only 10% of the infected children develop jaundice.
On the other hand, infection causes clinical disease among older children and adults, with jaundice occurring in more than 70% of cases. The good news is, once a person gets infected, life-long immunity to the virus is induced.
Prevention is possible through good hygiene practices. However, the best way to protect your child is through vaccination. The hepatitis A vaccine is now available in Malaysia for those above one year of age. Two doses given six months apart are required for full immunity against hepatitis A. The duration of protection is 14-20 years for children and at least 25 years for adults. It has also been reported that the vaccine is 85% effective in protecting against the virus.
Keep away from hepatitis B
Hepatitis B can cause chronic liver disease, which is potentially life-threatening. The chance of hepatitis B developing into a chronic disease depends on the age at which a person becomes infected. The younger you are, the higher the risk of a chronic infection. Chronic infection occurs in 90% of infants infected at birth, 30% of children infected at age one to five years and 6% of people infected after age five years.
The hepatitis B vaccine, the first vaccine indirectly related to the prevention of liver cancer, has been a mandatory vaccine under the National Immunisation Schedule since 1989. Since its introduction, there has been a decline in the number of Hepatitis B virus (HBV) carriers in our country. Full immunisation requires an administration of three doses. Hepatitis B vaccine is 90% effective in protecting against the virus, its chronic consequences, and liver cancer. Protection lasts at least 20 years and could be life-long.
Advancements in vaccines for hepatitis
A combination vaccine for hepatitis A and B is now available for those above 16 years of age. It combines inactivated hepatitis A and recombinant hepatitis B.
This combination vaccine consists of three doses. The first dose is followed by the second dose a month later, and the final dose is given six months after the first dose (0, 1, 6 month schedule).
It has been reported that the combination vaccine is more than 99% effective for hepatitis A and 93-97% effective for hepatitis B.
Technology today has made protection against hepatitis A and B available. There will be more hepatitis vaccines to come in the future.
THE liver is a vital organ in your body. It helps to process nutrients, remove toxins, fight off infections, store energy, and stop bleeding. To allow your liver to keep performing well, you need to protect your liver from various diseases, which can cause liver damage. One of the diseases that may harm your liver is hepatitis.
Hepatitis is an inflammation of the liver, most commonly caused by a viral infection. The five main hepatitis viruses are A, B, C, D, E and G.
Hepatitis A, B and C are the most common types of hepatitis diseases. They vary in terms of severity, means of spread, epidemic features, and preventive measures. Hepatitis can cause the liver to swell and lose its ability to function. It can also lead to cirrhosis (scarring), liver failure or cancer of the liver.
As a parent, you definitely want to keep your child healthy and protect him from this dreaded group of diseases. The good news is, vaccines are currently available for the prevention of hepatitis A and B.
Prevent hepatitis A
Hepatitis A is a disease which goes away within a few weeks. It rarely leads to permanent liver damage in healthy people. The hepatitis A virus is found in stools of the infected person. People most commonly get infected when they consume food or drinks that are contaminated with the infected person’s stool. Lightly cooked seafood like cockles contaminated by faeces or sewage provides a suitable medium to spread hepatitis A.
There is a chance of an outbreak in day-care centres because many young children wear diapers. If an infected child’s stool gets on their hands, they may contaminate the things they touch and transmit the virus to other children who touch these contaminated surfaces. Caregivers may also infect others if they do not wash their hands thoroughly after changing a child’s diaper.
Hepatitis can also spread through infected food handlers, consumption of undercooked oysters, clams, or mussels from contaminated waters, traveling to countries with poor sanitation, and injecting-drug users.
The risk of developing symptoms among people infected with hepatitis A is correlated with age. In children below 6 years of age, there are usually no symptoms. Only 10% of the infected children develop jaundice.
On the other hand, infection causes clinical disease among older children and adults, with jaundice occurring in more than 70% of cases. The good news is, once a person gets infected, life-long immunity to the virus is induced.
Prevention is possible through good hygiene practices. However, the best way to protect your child is through vaccination. The hepatitis A vaccine is now available in Malaysia for those above one year of age. Two doses given six months apart are required for full immunity against hepatitis A. The duration of protection is 14-20 years for children and at least 25 years for adults. It has also been reported that the vaccine is 85% effective in protecting against the virus.
Keep away from hepatitis B
Hepatitis B can cause chronic liver disease, which is potentially life-threatening. The chance of hepatitis B developing into a chronic disease depends on the age at which a person becomes infected. The younger you are, the higher the risk of a chronic infection. Chronic infection occurs in 90% of infants infected at birth, 30% of children infected at age one to five years and 6% of people infected after age five years.
The hepatitis B vaccine, the first vaccine indirectly related to the prevention of liver cancer, has been a mandatory vaccine under the National Immunisation Schedule since 1989. Since its introduction, there has been a decline in the number of Hepatitis B virus (HBV) carriers in our country. Full immunisation requires an administration of three doses. Hepatitis B vaccine is 90% effective in protecting against the virus, its chronic consequences, and liver cancer. Protection lasts at least 20 years and could be life-long.
Advancements in vaccines for hepatitis
A combination vaccine for hepatitis A and B is now available for those above 16 years of age. It combines inactivated hepatitis A and recombinant hepatitis B.
This combination vaccine consists of three doses. The first dose is followed by the second dose a month later, and the final dose is given six months after the first dose (0, 1, 6 month schedule).
It has been reported that the combination vaccine is more than 99% effective for hepatitis A and 93-97% effective for hepatitis B.
Technology today has made protection against hepatitis A and B available. There will be more hepatitis vaccines to come in the future.
Liver Transplant Allocation
Transplantation is the only treatment for end-stage liver failure, but suitable donor organs are in short supply. A new allocation scheme implemented in 2002 has improved racial disparities among transplant recipients, but women are still at a disadvantage, according to an analysis published in the November 26, 2008 Journal of the American Medical Association. C. Moylan and colleagues assessed the association between race, sex, and liver transplantation following introduction of the Model for End-Stage Liver Disease (MELD) system in February 2002. MELD estimates the risk of death within three months based on bilirubin and creatinine levels and prothrombin time. The researchers looked at a retrospective cohort of 21,895 adult patients on the United Network for Organ Sharing (UNOS) liver transplant waiting list between January 1996 and December 2000 (pre-MELD) and 23,793 patients added to the list between February 2002 and March 2006 (post-MELD).
Overall, black patients were younger and sicker than white patients on the waiting list during both periods. In the pre-MELD cohort, black patients were significantly more likely than whites to die or become too sick for transplantation within three years of registering on the waiting list (27.0% vs. 21.7%; odds ratio [OR] 1.51); blacks were also less likely than whites to receive a liver transplant during this period (61.6% vs. 66.9%; OR 0.75). By contrast, in the post-MELD cohort, black race was no longer associated with increased likelihood of death or becoming too sick for transplantation (26.5% vs. 22.0%; OR 0.96), and blacks were no less likely than whites to receive a transplant (47.5% vs. 45.5%; OR 1.04).
However, unlike the pre-MELD cohort, women were significantly more likely than men to die or become too sick for transplantation in the post-MELD period (23.7% vs. 21.4%; OR 1.30). Women were less likely than men to receive transplants within three years during both the pre-MELD (64.8% vs. 67.6%; OR 0.80) and post-MELD (39.9% vs. 48.7%; OR 0.70) periods. Following introduction of the MELD score, the researchers concluded, "race was no longer associated with receipt of a liver transplant or death on the waiting list, but disparities based on sex remain." They added that the elimination of the racial disparity likely reflects the fact that the MELD score accounts for the severity of disease when a patient is put on the waiting list. Women may receive fewer transplants due to their smaller size, since small donor livers may be used for large patients, but not vice versa.
Overall, black patients were younger and sicker than white patients on the waiting list during both periods. In the pre-MELD cohort, black patients were significantly more likely than whites to die or become too sick for transplantation within three years of registering on the waiting list (27.0% vs. 21.7%; odds ratio [OR] 1.51); blacks were also less likely than whites to receive a liver transplant during this period (61.6% vs. 66.9%; OR 0.75). By contrast, in the post-MELD cohort, black race was no longer associated with increased likelihood of death or becoming too sick for transplantation (26.5% vs. 22.0%; OR 0.96), and blacks were no less likely than whites to receive a transplant (47.5% vs. 45.5%; OR 1.04).
However, unlike the pre-MELD cohort, women were significantly more likely than men to die or become too sick for transplantation in the post-MELD period (23.7% vs. 21.4%; OR 1.30). Women were less likely than men to receive transplants within three years during both the pre-MELD (64.8% vs. 67.6%; OR 0.80) and post-MELD (39.9% vs. 48.7%; OR 0.70) periods. Following introduction of the MELD score, the researchers concluded, "race was no longer associated with receipt of a liver transplant or death on the waiting list, but disparities based on sex remain." They added that the elimination of the racial disparity likely reflects the fact that the MELD score accounts for the severity of disease when a patient is put on the waiting list. Women may receive fewer transplants due to their smaller size, since small donor livers may be used for large patients, but not vice versa.
Mother-to-Child HCV Transmission
Women with chronic hepatitis C may transmit HCV to their babies during pregnancy or delivery. This is uncommon overall – occurring at a rate of about 5% – but is more likely when the mother is HIV positive. As reported in the December 1, 2008 Journal of Infectious Diseases, K. Dowd and colleagues studied 63 HIV/HCV coinfected pregnant women to assess whether lower levels of HCV-specific neutralizing antibodies are associated with an increased risk of mother-to-child HCV transmission. Sixteen women (25%) transmitted HCV to their infants. There was no significant difference between transmitting and non-transmitting mothers in terms of the ability of maternal plasma to neutralize HCV (median neutralizing antibody titers of 1:125 vs. 1:100, respectively). "In the setting of HIV/HCV coinfection, we found no evidence that HCV neutralizing antibodies are associated with the prevention of mother-to-child transmission of HCV," the researchers concluded.
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