title: Lamivudine. A review of its therapeutic potential in chronic hepatitis B.
abstract: Lamivudine is a deoxycytidine analogue that is active against hepatitis B virus (HBV). In patients with chronic hepatitis B, lamivudine profoundly suppresses HBV replication. Clinically significant improvements in liver histology and biochemical parameters were obtained with lamivudine in double-blind, randomised, trials in hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B and compensated liver disease. After 52 weeks of treatment, relative to placebo (< or = 25%), significantly more Chinese (56%) or Western patients (52%) treated with lamivudine 100 mg/day had reductions of > or = 2 or more points in Knodell necro-inflammatory scores. Moreover, significantly fewer lamivudine 100 mg/day than placebo recipients had progressive fibrosis in liver biopsies (< or = 5 vs > or = 15%) and fewer lamivudine- than placebo-treated patients progressed to cirrhosis (1.8 vs 7.1%). More lamivudine 100 mg/day than placebo recipients acquired antibodies to HBeAg after 52 weeks (16 vs 4% in Chinese patients and 17 vs 6% in Western patients). ALT levels normalised in significantly more lamivudine than placebo recipients enrolled in these trials. In HBeAg-negative, HBV DNA positive patients with compensated liver disease enrolled in a double-blind, randomised study, HBV DNA levels were suppressed to below the limit of detection (< 2.5 pg/ml) and ALT levels normalised in 63% and 6% of patients treated with lamivudine 100 mg/day or placebo for 24 weeks. Clinically significant improvements in liver histology were obtained in 60% of patients treated with lamivudine for 52 weeks in this study. Lamivudine 100 mg/day for 52 weeks produced similar or significantly greater improvements in liver histology and ALT levels than 24 weeks' treatment with lamivudine plus interferon-alpha. In liver transplant candidates with chronic hepatitis B and end-stage liver disease, lamivudine 100 mg/day alone, or in combination with hepatitis B immune globulin, generally suppressed HBV replication and appeared to protect the grafted liver from reinfection. Lamivudine 100 mg/day suppressed viral replication and improved liver histology in liver transplant recipients with recurrent or de novo chronic hepatitis B. Lamivudine 300 or 600 mg/day reduced HBV replication in HIV-positive patients. The incidence of adverse events in patients with chronic hepatitis B and compensated liver disease treated with lamivudine 100 mg/day or placebo for 52 to 68 weeks was similar. 3.1- to 10-fold increases in ALT over baseline occurred in 13% of patients during treatment with lamivudine 100 mg/day or placebo for 52 weeks. Post-treatment ALT elevations were more common in lamivudine than placebo recipients; however, these generally resolved spontaneously; < or = 1.5% of lamivudine- or placebo-treated patients experienced hepatic decompensation.
  
  
  CONCLUSIONS
  Lamivudine inhibits HBV replication, reduces hepatic necro-inflammatory activity and the progression of fibrosis in patients with chronic hepatitis B, ongoing viral replication and compensated liver disease including HBeAg-negative patients. The drug also suppresses viral replication in liver transplant recipients and HIV-positive patients. Thus, lamivudine is potentially useful in a wide range of patients with chronic hepatitis B and ongoing viral replication.
authors.affiliation: Adis International Limited, Auckland, New Zealand. demail@adis.co.nz
authors.forename: B
authors.initials: B
authors.lastname: Jarvis
authors.forename: D
authors.initials: D
authors.lastname: Faulds
mesh_terms: D000818:Animals; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine