Long-term adefovir dipivoxil monotherapy for up to 5 years in lamivudine-resistant chronic hepatitis B.

BACKGROUND Large clinical studies assessing long-term adefovir dipivoxil salvage monotherapy in patients with lamivudine-resistant chronic hepatitis B (CHB) are lacking, particularly in patients positive for hepatitis B e antigen (HBeAg). We assessed the efficacy and resistance profile of adefovir dipivoxil monotherapy for up to 5 years in a large cohort of Korean patients with lamivudine-resistant CHB. METHODS A total of 320 patients (81.3% HBeAg-positive; 100% genotype C) with confirmed genotypic lamivudine-resistant CHB were switched to adefovir dipivoxil 10 mg once daily. Liver function tests and HBV DNA were monitored every 3 months. Genotypic resistance to adefovir dipivoxil was performed in patients with detectable HBV DNA. RESULTS The overall cumulative virological response rate at 5 years of adefovir dipivoxil therapy was 48.8%. The virological response rate was significantly higher in HBeAg-negative patients (62.0% versus 45.9%; P=0.010). Most cases of virological response (131/134, 97.8%) occurred within the first 36 months of therapy. The 5-year cumulative probability of genotypic resistance and virological breakthrough was 65.6% and 61.8%, respectively. Predictive factors for a virological response included baseline HBeAg seronegativity, HBV DNA< or =8 log(10) copies/ml and achievement of an on-treatment initial virological response. CONCLUSIONS Adefovir dipivoxil salvage monotherapy for lamivudine-resistant CHB resulted in a modest cumulative virological response rate at 5 years, which was associated with progressive antiviral resistance. Consequently, adefovir monotherapy is not preferable as a first-line strategy for lamivudine resistance where combination lamivudine plus adefovir dipivoxil therapy is available.