Virological and biochemical relapse after discontinuation of lamivudine monotherapy for chronic hepatitis B in Japan: comparison with breakthrough hepatitis during long-term treatment

Abstract

Objective: Comparison of virological and biochemical relapse in patients with chronic hepatitis B, based on continuation or discontinuation of lamivudine monotherapy.

Methods: In Japanese genotype C-dominant hepatitis B patients, 25 patients who stopped treatment at normal levels of alanine transferase (ALT) were retrospectively compared with 75 patients who continued treatment. Both groups were matched for age, sex, and observation period after start of treatment. We investigated the relapse rates, and evaluated predictive factors for relapse and efficacy of retreatment of the discontinuous group.

Results: Virological and biochemical relapse occurred significantly earlier in the discontinuous than continuous group, and the peak levels and ratios of peak to pretreatment levels of serum bilirubin and ALT after relapse were not significantly different between the two groups. Multivariate analysis identified three independent factors at discontinuation of treatment associated with early biochemical relapse: HBeAg positivity, presence of liver cirrhosis, detection of basic core promoter mutant. Normalization of ALT levels with retreatment occurred in 62.5% of patients, but 2 HBeAg-positive patients retreated after the emergence of YMDD motif mutant developed severe relapse with hyperbilirubinemia.

Conclusion: Our results in Japanese patients with genotype C-dominant hepatitis B suggest that discontinuation of lamivudine monotherapy, and retreatment after the emergence of YMDD mutant should be given attention.