Kuang-Wei Huang1, Ka-Wai Tam, Jiing-Chyuan Luo, Yi-Chun Kuan. 1. *Department of Internal Medicine, Division of Gastroenterology, Taipei Beitou, Health Management Hospital Departments of †Internal Medicine, Division of Gastroenterology and Hepatology §Surgery ††Neurology, School of Medicine, College of Medicine ∥Cochrane Taiwan, Taipei Medical University #Department of Internal Medicine, Division of Gastroenterology, Taipei Veterans General Hospital, Taipei Departments of ‡Surgery, Division of General Surgery **Neurology ¶Center for Evidence-Based Health Care, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan.
Abstract
BACKGROUND: Oral nucleos(t)ide analogs are recommended for patients with chronic hepatitis B virus (HBV)-related acute exacerbation (AE) and acute-on-chronic liver failure (ACLF). The efficacy and safety of administering entecavir (ETV) and lamivudine (LAM) to such patients remain unclear. METHODS: A comprehensive literature search was performed to select studies published before December 2015 on therapy involving ETV or LAM for chronic HBV-related AE with or without ACLF. The main outcomes were short-term (within 4 mo) and long-term (beyond 4 mo) mortality. The secondary outcomes were virological and biochemical responses, ACLF recurrence, and safety. RESULTS: Three prospective and 8 retrospective cohort studies involving 1491 patients were selected. An overall analysis revealed comparable short-term and long-term mortality rates among all patients who received ETV or LAM [short term: risk ratio (RR)=0.99; 95% confidence interval (CI), 0.78-1.27; long term: RR=0.82; 95% CI, 0.45-1.52]. However, in patients with ACLF, ETV yielded a more favorable long-term outcome than did LAM (RR=0.60; 95% CI, 0.45-0.80). Furthermore, ETV resulted in more efficient virological and biochemical responses than did LAM regarding the HBV DNA undetectable rate (RR=1.34; 95% CI, 1.09-1.63), HBV DNA reduction rate (weighted mean difference=-0.41; 95% CI, -0.69 to -0.13), and serum alanine aminotransferase normalization rate (RR=1.13; 95% CI, 1.05-1.21). CONCLUSIONS: ETV and LAM treatments exerted similar effects on the mortality rate of patients with chronic HBV-related AE with or without ACLF. However, ETV yielded a more favorable long-term outcome than did LAM in patients with ACLF; ETV was associated with greater clinical improvements. Additional larger, long-term randomized controlled trials are required to confirm these conclusions.
BACKGROUND: Oral nucleos(t)ide analogs are recommended for patients with chronic hepatitis B virus (HBV)-related acute exacerbation (AE) and acute-on-chronic liver failure (ACLF). The efficacy and safety of administering entecavir (ETV) and lamivudine (LAM) to such patients remain unclear. METHODS: A comprehensive literature search was performed to select studies published before December 2015 on therapy involving ETV or LAM for chronic HBV-related AE with or without ACLF. The main outcomes were short-term (within 4 mo) and long-term (beyond 4 mo) mortality. The secondary outcomes were virological and biochemical responses, ACLF recurrence, and safety. RESULTS: Three prospective and 8 retrospective cohort studies involving 1491 patients were selected. An overall analysis revealed comparable short-term and long-term mortality rates among all patients who received ETV or LAM [short term: risk ratio (RR)=0.99; 95% confidence interval (CI), 0.78-1.27; long term: RR=0.82; 95% CI, 0.45-1.52]. However, in patients with ACLF, ETV yielded a more favorable long-term outcome than did LAM (RR=0.60; 95% CI, 0.45-0.80). Furthermore, ETV resulted in more efficient virological and biochemical responses than did LAM regarding the HBV DNA undetectable rate (RR=1.34; 95% CI, 1.09-1.63), HBV DNA reduction rate (weighted mean difference=-0.41; 95% CI, -0.69 to -0.13), and serum alanine aminotransferase normalization rate (RR=1.13; 95% CI, 1.05-1.21). CONCLUSIONS:ETV and LAM treatments exerted similar effects on the mortality rate of patients with chronic HBV-related AE with or without ACLF. However, ETV yielded a more favorable long-term outcome than did LAM in patients with ACLF; ETV was associated with greater clinical improvements. Additional larger, long-term randomized controlled trials are required to confirm these conclusions.