title: Extended lamivudine treatment in patients with HBeAg-negative chronic hepatitis B.
abstract: OBJECTIVE
  The histological and clinical outcome of lamivudine 100mg/day was assessed in 76 HBeAg-negative chronic hepatitis B patients previously randomised to a double-blind comparison study of lamivudine and placebo.
  
  
  METHODS
  Paired liver biopsies were available before 1 year of randomised lamivudine treatment and after 2 years of further open-label treatment for 48 patients. Serum samples were analysed for hepatitis B markers and ALT levels (n=74).
  
  
  RESULTS
  The histological activity index improved, remained unchanged and worsened in 64, 32 and 5%, respectively, for patients without YMDD-variant HBV compared to 15, 54 and 31% with the variant. None of the 42/48 patients without cirrhosis at baseline progressed to cirrhosis. Of 24/48 patients without bridging fibrosis at pre-treatment, 83% (20/24) did not progress to bridging fibrosis. Median HBV DNA remained below the lower limit of detection and ALT < or =1 times the ULN for patients without the variant whereas levels gradually increased to 11.3Meq/ml (bDNA assay) and 2 times the upper limit of normal by month 24 for patients with variant.
  
  
  CONCLUSIONS
  The clinical benefit of lamivudine is greatest for patients without YMDD variants over 2 years of extended treatment. Additional therapies should be considered for patients with YMDD variants.
authors.affiliation: Experimental Department of Gastroenterology, San Giovanni Battista Hospital C.So Bramante, 88 10126 Turin, Italy. mario.rizzetto@unito.it
authors.forename: Mario
authors.initials: M
authors.lastname: Rizzetto
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Tassopoulos
authors.forename: Robert D
authors.initials: RD
authors.lastname: Goldin
authors.forename: Rafael
authors.initials: R
authors.lastname: Esteban
authors.forename: Teresa
authors.initials: T
authors.lastname: Santantonio
authors.forename: E Jenny
authors.initials: EJ
authors.lastname: Heathcote
authors.forename: Marco
authors.initials: M
authors.lastname: Lagget
authors.forename: Namrata K
authors.initials: NK
authors.lastname: Taak
authors.forename: Mary A
authors.initials: MA
authors.lastname: Woessner
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Gardner
mesh_terms: D004279:DNA, Viral / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine