Five years of treatment with adefovir dipivoxil in Chinese patients with HBeAg-positive chronic hepatitis B.

Background: Adefovir dipivoxil (ADV) is a nucleotide analogue with proven efficacy in chronic hepatitis B (CHB). Aims: This study investigated longterm ADV treatment in HBeAg-positive patients. Methods: A total of 480 Chinese subjects with HBeAg-positive CHB who participated in a 1-year, double-blind, placebo-controlled study of ADV 10 mg daily were offered open-label continuation for a further 208 weeks. Results: A total of 390 subjects completed 5 years of treatment. Baseline median hepatitis B virus (HBV) DNA was 8.8 log10 copies/ml and alanine aminotransferase (ALT) 2.6 9 upper limit of normal. Treatment with ADV resulted in sustained suppression of median HBV DNA by 4.8, 5.0, 5.1, 5.4 and 5.5 log10 copies/ml after 1, 2, 3, 4 and 5 years respectively. Continuous treatment with ADV led to a progressive increase in the proportion of subjects achieving undetectable HBV DNA, from 28% after 1 year to 58% after 5 years. HBeAg seroconversion rates increased cumulatively from 11% after 1 year to 29% after 5 years. HBsAg seroconversion was achieved by 1.0% of patients. ADV resulted in ALT normalization that was maintained throughout this study in 75-79% of subjects. Virological breakthrough associated with ADV resistant mutations (rtN236T and rtA181V) occurred in 14.6% of subjects. ADV was well tolerated. Conclusion: Five years of ADV treatment in Chinese subjects with HBeAg-positive CHB resulted in increasing virological and serological responses and sustained biochemical responses over time. Virological resistance was identified in 14.6% of patients. Urgent switch or add-on therapy with a nucleoside analogue is necessary if ADV resistant mutations are detected, particularly rtN236T. Treatment was well tolerated.