Huang Kuang-Wei, Tam Ka-Wai, Luo Jiing-Chyuan, Kuan Yi-Chun
*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.
J Clin Gastroenterol. 2017 Jul;51(6):539-547. doi: 10.1097/MCG.0000000000000675.
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.
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.
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).
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.
对于慢性乙型肝炎病毒（HBV）相关急性加重（AE）和慢加急性肝衰竭（ACLF）患者，推荐使用口服核苷（酸）类似物。在此类患者中应用恩替卡韦（ETV）和拉米夫定（LAM）的疗效和安全性仍不明确。
进行全面的文献检索，以筛选2015年12月之前发表的关于使用ETV或LAM治疗伴或不伴ACLF的慢性HBV相关AE的研究。主要结局为短期（4个月内）和长期（4个月后）死亡率。次要结局为病毒学和生化反应、ACLF复发及安全性。
选取了3项前瞻性和8项回顾性队列研究，共涉及1491例患者。总体分析显示，接受ETV或LAM治疗的所有患者的短期和长期死亡率相当[短期：风险比（RR）=0.99；95%置信区间（CI），0.78 - 1.27；长期：RR = 0.82；95% CI，0.45 - 1.52]。然而，在ACLF患者中，ETV的长期结局优于LAM（RR = 0.60；95% CI，0.45 - 0.80）。此外，在HBV DNA不可检测率（RR = 1.34；95% CI，1.09 - 1.63）、HBV DNA降低率（加权平均差 = -0.41；95% CI，-0.69至-0.13）和血清丙氨酸氨基转移酶正常化率（RR = 1.13；95% CI，1.05 - 1.21）方面，ETV导致的病毒学和生化反应比LAM更有效。
ETV和LAM治疗对伴或不伴ACLF的慢性HBV相关AE患者的死亡率有相似影响。然而，在ACLF患者中，ETV的长期结局优于LAM；ETV与更大的临床改善相关。需要更多大规模、长期的随机对照试验来证实这些结论。
