Entecavir monotherapy versus de novo combination of lamivudine and adefovir for compensated hepatitis B virus-related cirrhosis: a real-world prospective multicenter cohort study

Xiaoning Wu; Jialing Zhou; Wen Xie; Huiguo Ding; Xiaojuan Ou; Guofeng Chen; Anlin Ma; Xiaoyuan Xu; Hui Ma; Youqing Xu; Xiaoqing Liu; Tongtong Meng; Lin Wang; Yameng Sun; Bingqiong Wang; Yuanyuan Kong; Hong Ma; Hong You; Jidong Jia

doi:10.2147/IDR.S185120

Entecavir monotherapy versus de novo combination of lamivudine and adefovir for compensated hepatitis B virus-related cirrhosis: a real-world prospective multicenter cohort study

Infect Drug Resist. 2019 Apr 1:12:745-757. doi: 10.2147/IDR.S185120. eCollection 2019.

Authors

Xiaoning Wu^{1

2

3}, Jialing Zhou^{1

2

3}, Wen Xie⁴, Huiguo Ding⁵, Xiaojuan Ou^{1

2

3}, Guofeng Chen⁶, Anlin Ma⁷, Xiaoyuan Xu⁸, Hui Ma⁹, Youqing Xu¹⁰, Xiaoqing Liu¹¹, Tongtong Meng^{1

2

3}, Lin Wang^{1

2

3}, Yameng Sun^{1

2

3}, Bingqiong Wang^{1

2

3}, Yuanyuan Kong^{1

2

3}, Hong Ma^{1

2

3}, Hong You^{1

2

3}, Jidong Jia^{1

2

3}

Affiliations

¹ Liver Research Centre, Beijing Friendship Hospital, Capital Medical University, Beijing, China, jia_jd@ccmu.edu.cn; youhong30@sina.com.
² Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing, China, jia_jd@ccmu.edu.cn; youhong30@sina.com.
³ National Clinical Research Center of Digestive Diseases, Beijing, China, jia_jd@ccmu.edu.cn; youhong30@sina.com.
⁴ Liver Fibrosis Centre, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
⁵ Department of Digestive Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China.
⁶ Liver Fibrosis Centre, Beijing 302 Hospital, Beijing, China.
⁷ Department of Infectious Diseases, China-Japan Friendship Hospital, Beijing, China.
⁸ Department of Infectious Diseases, Peking University First Hospital, Beijing, China.
⁹ Liver Research Centre, Peking University People's Hospital, Beijing, China.
¹⁰ Department of Digestive Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
¹¹ Department of Infectious Diseases, Peking Union Medical College Hospital, Beijing, China.

Abstract

Background: De novo combination of lamivudine (Lam) and adefovir (Adv) was not rarely used in clinical practice. However, head-to-head comparisons of entecavir (Etv) monotherapy with this combination in hepatitis B virus (HBV)-related compensated cirrhosis patients are unavailable. This study aimed to compare the efficacy and safety of Etv monotherapy with combination therapy in patients with HBV-related compensated liver cirrhosis.

Methods: Treatment-naïve patients with HBV-related compensated liver cirrhosis were recruited to receive either Etv monotherapy or a de novo combination of Lam and Adv. Data were collected at baseline and every 6 months thereafter.

Results: A total of 578 patients (485 in Etv group, 93 in combination group) were included. Baseline characteristics were comparable between the two groups. At the end of 1, 2, and 3 years, HBV DNA was undetectable in 82.7%, 96.2%, and 94.3% of patients in the Etv group and 88.9%, 81.7%, and 84.6% in the combination group, respectively (all P>0.05). The cumulative virological breakthrough rate at 1, 2, and 3 years was 2.7%, 6.7%, and 9.8% in the Etv group and 2.9%, 13.3%, and 32.2% in the combination group, respectively (P=0.003). After propensity-score adjustment for age, sex, and baseline HBeAg, ALT, and total bilirubin, virological breakthrough was higher in the de novo combination of Lam and Adv (HR 2.83, 95% CI 1.37-5.86; P<0.01). The cumulative rate of liver-related events, including decompensation and hepatocellular carcinoma, at 1, 2, and 3 years was 2.9%, 4.2%, and 6.1% in the Etv group and 2.2%, 2.2%, and 6.7% in combination group, respectively (P=0.83). Biochemical response and serological response were similar between the groups.

Conclusion: Etv treatment had less virological breakthrough and potentially higher HBV-DNA suppression than de novo combination of Lam and Adv during 3 years in treatment-naïve HBV-related compensated liver cirrhosis.

Keywords: adefovir; compensated HBV-related cirrhosis; de novo combination; entecavir; lamivudine; real-world; virological breakthrough.