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An estimated 15% to 25% of patients with chronic hepatitis B die of complications of the disease, such as cirrhosis and liver cancer.

In 2000, interferon monotherapy was the first-line treatment for chronic hepatitis B. This article examines the results of trials of peginterferon and nucleoside/nucleotide analogues (adefovir, entecavir, lamivudine), through a systematic review of the literature based on standardised Prescrire methodology.

We found no significant new data on interferon alfa administered subcutaneously three times a week: this treatment leads to sustained eradication of HBe antigen (reflecting a lack of viral replication) in 20% to 40% of patients. Adverse effects include a flu-like syndrome, potentially severe psychiatric disorders, and haematological and thyroid problems.

A trial comparing peginterferon alfa- 2a once a week with interferon alfa-2a three times a week in about 300 patients showed that peginterferon alfa was at least as effective as interferon alfa-2a but that it increased the risk of neutropenia.

Three randomised controlled trials show that adding lamivudine to peginterferon does not increase the effect on viral load.Two trials show that peginterferon alfa-2a monotherapy is more effective than lamivudine monotherapy at 48 weeks.

In a randomised placebo-controlled trial in more than 600 cirrhotic patients, lamivudine (100 mg/day) reduced the risk of clinical progression in 10% of patients after three years of treatment.

The adverse effects of lamivudine are generally mild. Viral resistance occurs frequently and can limit its use.

Randomised controlled trials of adefovir dipivoxil show that it is effective after lamivudine failure, and that viral resistance tends to occur later than with lamivudine.When used as firstline treatment, adefovir dipivoxil is virologically effective for at least two years in about 25% of patients. Fewer follow-up data are available for adefovir dipivoxil than for lamivudine. Adefovir dipivoxil is nephrotoxic, meaning that blood creatinine levels must be monitored.

Entecavir was more effective than lamivudine on viral load and histological inflammation in three comparative trials lasting 96 weeks. However, entecavir may be carcinogenic.

In short, the treatment options for patients with chronic hepatitis B improved significantly between 2000 and 2007. Peginterferon alfa is now the first choice treatment, followed by adefovir dipivoxil or lamivudine as secondline treatment and by entecavir as a last resort. Other antivirals are under development.

©Prescrire August 2007

Source: Prescrire International 2007; 16 (90): 157-162.

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