Lamivudine compared with lamivudine and adefovir dipivoxil for the treatment of HBeAg-positive chronic hepatitis B.

BACKGROUND/AIMS: We aimed to evaluate nucleoside/nucleotide combination therapy in treatment-naïve HBeAg-positive patients with chronic hepatitis B (CHB). METHODS: One hundred and fifteen HBeAg-positive patients received lamivudine 100 mg daily plus placebo (monotherapy) or lamivudine 100 mg plus adefovir dipoxil 10 mg daily (combination therapy) for 104 weeks in a randomized double-blind study. RESULTS: Time-weighted average change in serum HBV DNA from baseline up to week 16 was -4.20 log(10)copies/mL for both groups (p=0.936). At week 104, median serum HBV DNA change from baseline (log(10)copies/mL) for monotherapy and combination therapy was -3.41 versus -5.22, respectively. HBV DNA breakthrough was detected in 44% of monotherapy and 19% of combination therapy patients. The M204V/I mutation was detected in 43% (15/35) and 15% (6/41) of each group, respectively. ALT normalization at week 100 and 104 was 34% (19/56) in the monotherapy group and 45% (23/51) in the combination therapy group (p=0.018). By week 104, HBeAg seroconversion occurred in 20% of monotherapy and 13% of combination therapy patients. Both regimens were well tolerated. CONCLUSIONS: Lower rates of resistance to lamivudine, lower serum HBV DNA levels and higher rates of ALT normalization were seen in the combination therapy group after two years. However, serological outcomes were similar.

Extended lamivudine treatment in patients with HBeAg-negative chronic hepatitis B.

BACKGROUND/AIMS: 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.

Lamivudine and 24 weeks of lamivudine/interferon combination therapy for hepatitis B e antigen-positive chronic hepatitis B in interferon nonresponders.

BACKGROUND/AIMS: Lamivudine is effective in treatment-naive patients with chronic hepatitis B, but its role in interferon nonresponders has not been described. We assessed lamivudine treatment, with or without added interferon, in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B who had failed interferon therapy previously. METHODS: Patients were randomized to lamivudine (100 mg) or placebo for 52 weeks or to a 24-week regimen of lamivudine plus interferon. Primary treatment comparisons were at week 52, with a 16-week posttreatment follow-up period. Measurements included histology (primary endpoint), HBeAg response, normalization of alanine aminotransferase, reduction of hepatitis B virus (HBV) DNA, and safety. RESULTS: Among 238 patients, histologic response was significantly more common in patients treated with lamivudine (52 versus placebo 25%, P=0.002) or the combination regimen (32%, P=0.01). HBeAg loss was also more common with lamivudine (33 versus 13 versus 21%), as were virologic and alanine aminotransferase responses. Among 28 subjects with HBeAg loss/seroconversion, 71% had durable responses 16 weeks posttreatment. CONCLUSIONS: Lamivudine for 52 weeks is as effective in interferon nonresponders as in previously reported treatment-naive patients; however, a combination of lamivudine for 24 weeks and interferon for 16 weeks was not effective in this population.