Extended lamivudine treatment in patients with HBeAg-negative chronic hepatitis B.
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.
Rizzetto
Mario
M
Experimental Department of Gastroenterology, San Giovanni Battista Hospital C.So Bramante, 88 10126 Turin, Italy. mario.rizzetto@unito.it
Tassopoulos
Nicholas C
NC
Goldin
Robert D
RD
Esteban
Rafael
R
Santantonio
Teresa
T
Heathcote
E Jenny
EJ
Lagget
Marco
M
Taak
Namrata K
NK
Woessner
Mary A
MA
Gardner
Stephen D
SD
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
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine