Lamivudine therapy for hepatitis B infection.
Several new antiviral agents have recently 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 are in progress, or have been completed. The sustained HBeAg seroconversion rate in patients who have received 100 mg lamivudine rate increase from 17% at year one to 27% after 2 years. Early treatment results have suggested that lamivudine improves hepatic histology in patients with chronic hepatitis B, and 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 substantially reduce the burden of infected hepatocytes in the liver, and prevent relapse. Histological improvement has been noted in between 38% and 52% of lamivudine-treated patients, exceeding the improvement seen in placebo recipients. Lamivudine has also been assessed in anti-HBe positive, HBV DNA positive patients. Preliminary results show that 65% of lamivudine recipients become HBV DNA negative and have normal serum aminotransferases after a year of treatment. The drug is generally well tolerated with few direct adverse events. Genotypic mutations have been observed in 11% after 1 year of treatment, but this percentage doubles after 2 years of therapy. Loss of susceptibility 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. Both HBeAg and anti-HBe positive patients are benefited, as may be patients with cirrhosis.
Dusheiko
G
G
Royal Free Hospital and School of Medicine, London, UK.
D004279:DNA, Viral / Q000032:analysis / Q000187:drug effects; D006509:Hepatitis B / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology / Q000821:virology; D006513:Hepatitis B e Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D055502:Secondary Prevention; D000637:Transaminases / Q000097:blood; D016896:Treatment Outcome; D014779:Virus Replication / Q000187:drug effects
D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D000637:Transaminases