title: Efficacy and Safety of Lamivudine Versus Entecavir for Treating Chronic Hepatitis B Virus-related Acute Exacerbation and Acute-on-Chronic Liver Failure: A Systematic Review and Meta-Analysis.
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.
authors.affiliation: *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.
authors.forename: Kuang-Wei
authors.initials: KW
authors.lastname: Huang
authors.forename: Ka-Wai
authors.initials: KW
authors.lastname: Tam
authors.forename: Jiing-Chyuan
authors.initials: JC
authors.lastname: Luo
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Kuan
mesh_terms: D065290:Acute-On-Chronic Liver Failure / Q000188:drug therapy* / Q000401:mortality / Q000821:virology; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019694:Hepatitis B, Chronic / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
chemical_list: D000998:Antiviral Agents; D019259:Lamivudine; C413685:entecavir; D006147:Guanine