Serper M, Forde K A, Kaplan D E
Gastroenterology Section, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.
Center for Health Equity Research and Promotion, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.
J Viral Hepat. 2018 Feb;25(2):187-197. doi: 10.1111/jvh.12784. Epub 2017 Sep 21.
Recently, cases of hepatitis B virus reactivation (HBVr) with direct-acting antiviral therapy (DAAs) for HCV have been reported. However, few data exist from large, Western cohorts. The study objectives were to evaluate the incidence of alanine aminotransferase (ALT) flares, clinically significant hepatic events, and HBVr among a national cohort of US veterans with prior exposure to HBV (anti-HBc+) treated with DAAs. We used a national administrative database to identify patients treated with DAAs from January 2014 through November 2016 and obtained clinical and demographic as well as HBV and HCV treatment data. HBVr was defined as an at least 1-log increase in HBV DNA titre. Among 17 779 anti-HBc+ patients, 17 400 were HIV- and 379 were HIV+. Among the HIV- patients, 17 266 (99%) were HBsAg- prior to DAA therapy and 134 were HBsAg+. Among HIV-, HBsAg- patients, ALT elevations greater than 10 times the upper limit of normal (ULN; ≥300 IU/mL) were rare and occurred more frequently after treatment completion: 31 cases (<0.1%) during vs 85 (0.6%) following treatment. Clinically significant hepatic events defined as ALT increases >100 IU/L with total bilirubin >2.5 mg/dL occurred in 39 cases (0.3%), most often following DAA completion (n = 35 cases, 3/35 in setting of HCV relapse). Among 31 patients with post-DAA hepatic events without HCV relapse, 10 (32%) were confirmed unrelated to HBVr by HBsAg and/or HBV DNA testing, 1 (3%) confirmed due to HBVr, and 20 (65%) did not have documented HBV-related testing. One additional case of HBsAg- to + seroreversion was identified. Among HBsAg+ DAA recipients, 2/97 (2%), both with cirrhosis, experienced ALT elevations ≥300 IU/mL in the setting of HBVr. In conclusion, clinically significant hepatic events and HBVr were rare and much more likely among HBsAg-positive individuals. Anti-HBc + patients should be monitored for ALT flares and HBVr during and possibly for up to 6 months post-DAA therapy.
最近，有报告称使用丙型肝炎直接抗病毒疗法（DAA）后出现了乙型肝炎病毒再激活（HBVr）的病例。然而，来自西方大型队列的数据很少。本研究的目的是评估在美国一组曾接触过HBV（抗-HBc阳性）的退伍军人中，接受DAA治疗后丙氨酸转氨酶（ALT）升高、具有临床意义的肝脏事件和HBVr的发生率。我们使用了一个全国性的行政数据库来识别2014年1月至2016年11月期间接受DAA治疗的患者，并获取了临床、人口统计学以及HBV和HCV治疗数据。HBVr被定义为HBV DNA滴度至少升高1个对数。在17779例抗-HBc阳性患者中，17400例为HIV阴性，379例为HIV阳性。在HIV阴性患者中，17266例（99%）在接受DAA治疗前HBsAg阴性，134例HBsAg阳性。在HIV阴性、HBsAg阴性患者中，ALT升高超过正常上限10倍（ULN；≥300 IU/mL）的情况很少见，且在治疗完成后更频繁发生：治疗期间31例（<0.1%），治疗后85例（0.6%）。定义为ALT升高>100 IU/L且总胆红素>2.5 mg/dL的具有临床意义的肝脏事件发生在39例（0.3%）患者中，大多发生在DAA治疗完成后（35例，其中3/35例发生在HCV复发时）。在31例DAA治疗后出现肝脏事件且无HCV复发的患者中，10例（32%）经HBsAg和/或HBV DNA检测证实与HBVr无关，1例（3%）证实为HBVr所致，20例（65%）未进行HBV相关检测。另外还发现1例HBsAg从阴性转为阳性的血清学转换病例。在HBsAg阳性的DAA接受者中，97例中有2例（2%），均患有肝硬化，在HBVr情况下出现ALT升高≥300 IU/mL。总之，具有临床意义的肝脏事件和HBVr很少见，在HBsAg阳性个体中更有可能发生。抗-HBc阳性患者在DAA治疗期间以及可能在治疗后长达6个月内应监测ALT升高和HBVr情况。
