Sae Hwan Lee1, Gab Jin Cheon2, Hong Soo Kim1, Sang Gyune Kim3, Young Seok Kim3, Soung Won Jeong4, Jae Young Jang4, Boo Sung Kim4, Baek Gyu Jun2, Young Don Kim2, Dae Won Jun5, Joo Hyun Sohn6, Tae Yeob Kim7, Byung Seok Lee8. 1. Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Korea. 2. Department of Internal Medicine, University of Ulsan College of Medicine, Gangneung Asan Hospital, Gangneung, Korea. 3. Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea. 4. Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea. 5. Department of Internal Medicine, Hanyang University Seoul Hospital, Seoul, Korea. 6. Department of Internal Medicine, Hanyang University Guri Hospital, Guri, Korea. 7. Institute of Medical Science, Hanyang University, Seoul, Korea. 8. Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Korea.
Abstract
BACKGROUND: A complete virological response is closely related to the long-term outcome of patients with chronic hepatitis B and prevention of emerging HBV mutations. We aimed to evaluate the efficacy of tenofovir disoproxil fumarate (TDF) monotherapy compared to entecavir-adefovir dipivoxil (ETV-ADV) combination therapy in patients with suboptimal responses to long-term lamivudine-adefovir dipivoxil (LAM-ADV) therapy for nucleoside analogue-resistant chronic hepatitis B. METHODS: Patients (n=60) were randomized to TDF monotherapy or ETV-ADV combination therapy for 96 weeks. All patients had the rt204I/V mutation and serum HBV DNA was measured (>60 IU/ml) during LAM-ADV therapy. The primary end point was a complete virological response (HBV DNA <20 IU/ml) at week 96. RESULTS: The median duration of prior LAM-ADV rescue therapy was 43 (7-108) months. A complete virological response was achieved in 86.6% and 53.3% of patients in the TDF and ETV-ADV groups, respectively, at week 96 (P=0.005). Reduction in serum HBV DNA was significantly greater in the TDF group than in ETV-ADV group (-3.2 ±1.2 versus -2.6 ±1.2; P=0.01). Hepatitis B e antigen loss (22.2% versus 16.6%; P=0.731) and biochemical responses (76.7% versus 73.3%; P=0.766) were not different between the TDF and ETV-ADV groups. No newly emerged mutations were detected. Both therapies demonstrated favourable safety profiles. CONCLUSIONS:TDF therapy achieved a better complete virological response than ETV-ADV therapy in chronic hepatitis B patients with suboptimal response to long-term LAM-ADV rescue therapy. (KCT0000627).
RCT Entities:
BACKGROUND: A complete virological response is closely related to the long-term outcome of patients with chronic hepatitis B and prevention of emerging HBV mutations. We aimed to evaluate the efficacy of tenofovir disoproxil fumarate (TDF) monotherapy compared to entecavir-adefovirdipivoxil (ETV-ADV) combination therapy in patients with suboptimal responses to long-term lamivudine-adefovirdipivoxil (LAM-ADV) therapy for nucleoside analogue-resistant chronic hepatitis B. METHODS:Patients (n=60) were randomized to TDF monotherapy or ETV-ADV combination therapy for 96 weeks. All patients had the rt204I/V mutation and serum HBV DNA was measured (>60 IU/ml) during LAM-ADV therapy. The primary end point was a complete virological response (HBV DNA <20 IU/ml) at week 96. RESULTS: The median duration of prior LAM-ADV rescue therapy was 43 (7-108) months. A complete virological response was achieved in 86.6% and 53.3% of patients in the TDF and ETV-ADV groups, respectively, at week 96 (P=0.005). Reduction in serum HBV DNA was significantly greater in the TDF group than in ETV-ADV group (-3.2 ±1.2 versus -2.6 ±1.2; P=0.01). Hepatitis B e antigen loss (22.2% versus 16.6%; P=0.731) and biochemical responses (76.7% versus 73.3%; P=0.766) were not different between the TDF and ETV-ADV groups. No newly emerged mutations were detected. Both therapies demonstrated favourable safety profiles. CONCLUSIONS:TDF therapy achieved a better complete virological response than ETV-ADV therapy in chronic hepatitis Bpatients with suboptimal response to long-term LAM-ADV rescue therapy. (KCT0000627).