Lamivudine treatment of chronic hepatitis B.

Abstract

Several new nucleoside analogues have been developed which can inhibit hepatitis B replication by at least two logs. Lamivudine is the most widely studied of these new agents. Extensive phase II and III studies in patients with chronic hepatitis B have been completed. The sustained HBeAg seroconversion rate in patients who have received 100 mg lamivudine increases from 17% after a year of treatment to 27% after 2 years of treatment. Histological improvement has been noted in 38%-52% of lamivudine-treated patients, exceeding the improvement seen in placebo recipients. Similar histological improvement has been noted in anti-HBe-positive, DNA- positive patients. Lamivudine can prevent recurrence of hepatitis B after liver transplantation. It is likely that in the absence of immune clearance to accelerate elimination of infected hepatocytes, inhibitors of virus replication such as lamivudine will need to be administered for a long period to reduce the burden of infected hepatocytes in the liver, and to prevent relapse. The drug is generally well tolerated with few direct adverse events. Genotypic mutations have been observed in 23% (range 13-32%). In a study in Asian patients treated for two years the incidence of these mutants increased to 38% (as detected by PCR). Loss of susceptibility to lamivudine has been found to be due to reverse transcriptase amino acid substitutions. Lamivudine is likely to be reserved for patients with replicative hepatitis B infection with active chronic hepatitis, and/or active cirrhosis. Copyright 1998 John Wiley & Sons, Ltd.