Outcome of lamivudine-resistant chronic hepatitis B after up to 5 years of combination therapy with adefovir

Background: There is a paucity of data on the long-term efficacy of combination lamivudine and adefovir therapy in patients with lamivudine-resistant chronic hepatitis B. Methods: We determined the cumulative virological, serological and biochemical outcomes of 165 lamivudine-resistant chronic hepatitis B patients on lamivudine and adefovir for up to 5 years. Resistance profiles using a line probe assay were determined among patients with detectable viraemia. The significance of different baseline and on-treatment virological parameters was analysed. Results: The median age and duration of follow-up were 45.1 years and 37.1 months, respectively. The cumulative rates of HBV DNA undetectability (<20 IU/ml), alanine aminotransferase normalization and hepatitis B e antigen seroconversion up to 5 years were 74.0%, 95.1% and 44.4%, respectively. One patient achieved hepatitis B surface antigen seroclearance. The 5-year cumulative resistance rate to adefovir was 10.2%. Among different baseline and on-treatment virological parameters, week 24 HBV DNA<200 IU/ml was associated with an increased chance of long-term virological suppression (P<0.001, OR 13.89, 95% CI 3.90, 49.46). Primary non-response and high baseline viral titres were not useful in predicting long-term virological outcomes. The 5-year cumulative rate of serum creatinine elevation >0.5 mg/dl was 4.1%. Conclusions: Combination lamivudine and adefovir therapy for up to 5 years achieved modest rates of virological suppression, but resistance developed in only 10.2% of patients. Week 24 HBV DNA<200 IU/ml was predictive of favourable long-term virological outcomes and could be used to assist treatment decisions on continuing lamivudine and adefovir or switching to more potent therapy.