Advance Against Hepatitis B

Long-term treatment with entecavir, an inhibitor of hepatitis B virus (HBV) replication, reduces cirrhosis and fibrosis in patients with chronic hepatitis B infection, report Eugene Schiff et al. in the March issue of Clinical Gastroenterology and Hepatology

Patients with chronic hepatitis B can develop liver fibrosis or cirrhosis and have high risks for additional complications, such as liver cancer. Entecavir is a nucleoside analog that has been shown to be effective in patients with chronic hepatitis B, based on histologic, virologic and biochemical responses. Schiff et al. evaluated the efficacy and safety of long-term treatment with entecavir in patients with cirrhosis or fibrosis. 

The authors followed 10 male patients who had cirrhosis or advanced fibrosis and had already received entecavir in phase 3 studies; they then received entecavir in an open-label rollover study. After an average of 6 years of treatment with entecavir, all of the patients had improved liver histology and lower fibrosis scores, which were reduced to noncirrhotic levels (see below figure).

Knodell necroinflammatory scores from biopsy samples, collected when the phase 3 study began (baseline), after 48 weeks of entecavir therapy and after a median time of 6 years.

Furthermore, the level of HBV DNA became undetectable, and 9 of the patients had normal levels of alanine aminotransferase, indicating normal liver function. None of the patients discontinued therapy because of adverse events.

Advanced liver fibrosis and cirrhosis were considered to be irreversible until recently, when laboratory and clinical evidence showed otherwise. However, there are limited data on the long-term impact of antiviral therapy on cirrhosis. Although other anti-HBV drugs such as lamivudine and adefovir can reverse fibrosis and cirrhosis, their long-term efficacy is limited by the development of drug-resistant variants.

Entecavir is a more potent inhibitor of HBV replication than other nucleoside analogs (lamivudine, lobucavir, ganciclovir, acyclovir and penciclovir) that are active against lamivudine-resistant HBV. The authors proposed that improvements they observed after long-term treatment with entecavir might result from sustained viral suppression.

Current treatment guidelines recommend that patients with cirrhosis receive long-term treatment with an antiviral drug with a low risk of resistance. Schiff et al. conclude that entecavir is a potent antiviral agent that sets a high barrier for HBV resistance mutations and should be included in the long-term management of patients with advanced fibrosis or cirrhosis.

More Information on Entecavir and Cirrhosis:

Read the article online:
Schiff ER, Lee SS, and Chao Y-C. Long-term treatment with entecavir induces reversal of advanced fibrosis or cirrhosis in patients with chronic hepatitis B. Clin Gastroenterol and Hepatol 2011;9:274–276.e1.

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About Kristine Novak, PhD, Science Editor

Dr. Kristine Novak is the science editor for Gastroenterology and Clinical Gastroenterology and Hepatology, both published by the American Gastroenterological Association. She has worked as an editor at biomedical research journals and as a science writer for more than 12 years, covering advances in gastroenterology, hepatology, cancer, immunology, biotechnology, molecular genetics, and clinical trials. She has a PhD in cell biology and an interest in all areas of medical research.
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