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Treatment of chronic hepatitis B

Nature Clinical Practice Gastroenterology & Hepatology volume 3, pages 446–458 (2006)Cite this article

Abstract

Treatment of chronic hepatitis B has improved substantially over the past five years. Pegylated interferon α2a and entecavir have been approved by the FDA and joined the armamentarium of therapies that includes inteferon α (IFN-α), lamivudine, and adefovir dipivoxil. Several key questions come to mind regarding treatment. Who should receive treatment? Which agent should they be given? How long should treatment last? Treatment is indicated for patients with a high pretreatment alanine aminotransferase level, detectable HBV DNA, and active inflammation on liver biopsy. When selecting an agent, the likelihood of achieving a sustained response should be weighed against long-term risks. IFN-α, lamivudine, and adefovir dipivoxil are equally efficacious; however, even though IFN-α and pegylated IFN-α have a durable response, both are associated with unpleasant side effects. Long-term lamivudine therapy has a high rate of drug resistance compared with adefovir dipivoxil, which has a low rate of drug resistance and a small risk of reversible nephrotoxicity. Entecavir reduces HBV load more effectively than the other therapies, but it is associated with increased drug resistance in patients with lamivudine-resistant HBV. The key to therapy seems to be some combination of therapies—both existing and those in development—that has yet to be determined.

Key Points

  • The goal of therapy for chronic hepatitis B is to prevent cirrhosis, hepatic decompensation or failure, and hepatocellular carcinoma

  • The aim of treatment is to suppress HBV to a nondetectable level, because eradication of HBV is impossible with the drugs currently available

  • Treatment is clearly indicated for patients with high ALT levels, detectable HBV DNA, and active inflammation in the liver biopsy, taking into account side effects, a sustained response rate, and long-term risks (e.g. drug resistance)

  • Lamivudine is not widely accepted as a first-line therapy because of the high rate of drug resistance that develops with its long-term use—the best first-line therapy remains to be determined

  • Choosing the best drug from the many new therapies available is a challenge

  • The decision to treat and the choice of treatment should be made on an individual basis, by the physician and the patient

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Figure 1: Mutations in HBV that confer resistance to antiviral drugs.
Figure 2: A summary of the resistance rates for lamivudine, adefovir dipivoxil, and entecavir.

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Authors and Affiliations

  1. Assistant Professor of Medicine Department of Medicine, Section of Gastroenterology, University of Chicago, Chicago, IL, USA

    Smruti R Mohanty

  2. Gastroenterology Fellow, Department of Medicine, Section of Gastroenterology, University of Chicago, Chicago, IL, USA

    Sonia S Kupfer

  3. Internal Medicine Resident, Department of Medicine, The Case Western Reserve University, Cleveland, OH, USA

    Vijay Khiani

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  1. Smruti R Mohanty
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  2. Sonia S Kupfer
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  3. Vijay Khiani
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Correspondence to Smruti R Mohanty.

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Competing interests

S Mohanty is a member of the speakers bureau for chronic hepatitis B, supported by Bristol Myers Squib (PoMS) and Gilead Sciences. SS Kupfer and V Khiani declared they have no competing interests.

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Mohanty, S., Kupfer, S. & Khiani, V. Treatment of chronic hepatitis B. Nat Rev Gastroenterol Hepatol 3, 446–458 (2006). https://doi.org/10.1038/ncpgasthep0550

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