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

Hyun Seok Lee,; Soo Young Park,; So Young Choi,; Min Kyu Jung,; Seong Woo Jeon,; Chang Min Cho,; Young Oh Kweon,; Sung Kook Kim,; Yong Hwan Choi,; Won Young Tak,

Korean J Med > Volume 77(6); 2009 > Article

Original Article

The Korean Journal of Medicine 2009;77(6):716-722.

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

Hyun Seok Lee, Soo Young Park, So Young Choi, Min Kyu Jung, Seong Woo Jeon, Chang Min Cho, Young Oh Kweon, Sung Kook Kim, Yong Hwan Choi, Won Young Tak

라미부딘 내성 만성 B형 간염 환자에서 라미부딘과 아데포비어 병용치료

이현석, 박수영, 최소영, 정민규, 전성우, 조창민, 권영오, 김성국, 최용환, 탁원영

Abstract

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.

Key Words: Lamivudine; Hepatitis B, Chronic; Adefovir; Drug resistance