Lamivudine and adefovir combination therapy in patients with lamivudine-resistant HBeAg-positive chronic hepatitis B

Background/Aims: This study assessed the clinical efficacy of lamivudine-adefovir combination therapy and adefovir monotherapy for 96 weeks in patients who had hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) with genotypic resistance to lamivudine. Methods: We reviewed 134 patients who had HBeAg-positive CHB with genotypic resistance to lamivudine. We assessed liver function tests, hepatitis B virus (HBV) DNA, HBeAg, and antibody every 12 weeks after adefovir treatment. We searched for adefovir-related mutations in patients with biochemical or virologic breakthrough after adefovir treatment. Results: Data on 34 patients receiving combination therapy and 100 patients receiving monotherapy were analyzed. After 96 weeks, 82.4% of the combination therapy and 69.0% of the monotherapy patients had normalized alanine aminotransferase (ALT) levels (p=0.132). In addition, 50.0% and 37.0% achieved undetectable HBV DNA (p=0.210), respectively, and 23.5% and 20.0% lost HBeAg (p=0.662). The combination therapy group (5.9%) showed significantly lower biochemical breakthrough than the monotherapy group (22.0%, p=0.034) and had a lower cumulative biochemical breakthrough rate (p=0.043). One patient (2.9%) receiving combination therapy and 11 patients (11.0%) receiving monotherapy developed genotypic resistance to adefovir (p=0.155). One rtA181V mutation was detected in the combination therapy group, and ten rtA181V mutations and one rtN236T mutation were detected in the monotherapy group. Conclusions: Combination therapy had higher rates of ALT normalization, undetectable HBV DNA, and HBeAg loss and a lower rate of adefovir resistance. Monotherapy had significantly higher biochemical breakthrough and cumulative biochemical breakthrough rates than combination therapy. Therefore, combination therapy was clinically more effective than monotherapy. (Korean J Med 77:716-722, 2009)