Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt am Main, Germany.
Department of Veterans Affairs, Population Health Services, Palo Alto Health Care System, Palo Alto, CA, USA.
Lancet Gastroenterol Hepatol. 2018 Mar;3(3):172-180. doi: 10.1016/S2468-1253(18)30002-5. Epub 2018 Jan 19.
Direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection might pose a risk for hepatitis B virus (HBV) reactivation in patients coinfected with chronic or resolved HBV infection. The need for HBV antiviral prophylaxis during DAA treatment remains controversial. We aimed to analyse the absolute risk of HBV reactivation in patients with active or resolved HBV infection treated with DAAs for HCV infection.
For this systematic review and meta-analysis, we searched PubMed, Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, and Web of Science from Oct 1, 2010, to Sept 30, 2017, to identify studies of patients with chronic or resolved HBV infection at baseline treated with DAAs for chronic HCV infection. Conference proceedings, abstract books, and references from relevant reviews were also examined for potential studies. Two independent researchers extracted data and assessed quality and risk of bias. Data were pooled by use of random-effects models. The primary outcome was HBV reactivation defined by standardised nomenclature. This study is registered with PROSPERO, number CRD42017065882.
We identified 17 observational studies involving 1621 patients with chronic (n=242) or resolved (n=1379) HBV infection treated with different DAAs. The pooled proportion of patients who had HBV reactivation was 24% (95% CI 19-30) in patients with chronic HBV infection and 1·4% (0·8-2·4) in those with resolved HBV infection. In patients with chronic HBV infection, the pooled proportion of patients with HBV-reactivation-related hepatitis was 9% (95% CI 5-16) and the relative risk (RR) of HBV-reactivation-related hepatitis was significantly lower in patients with HBV DNA below the lower limit of quantification at baseline than in those with quantifiable HBV DNA (RR 0·17, 95% CI 0·06-0·50; p=0·0011). Three major clinical events related to HBV reactivation in patients with chronic HBV infection were reported (one patient had liver decompensation and two had liver failure, one of whom required liver transplantation). In patients with resolved HBV infection, no HBV-reactivation-related hepatitis was reported.
HBV reactivation occurs frequently in patients with chronic HBV and HCV coinfection receiving DAA therapy but is rare among patients with resolved HBV infection. Use of antiviral prophylaxis might be warranted in patients who test positive for hepatitis B surface antigen (HBsAg), particularly those with quantifiable HBV DNA.
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直接作用抗病毒（DAA）疗法治疗慢性丙型肝炎病毒（HCV）感染可能会导致慢性或已解决的乙型肝炎病毒（HBV）感染患者发生乙型肝炎病毒（HBV）再激活。在 DAA 治疗期间是否需要进行 HBV 抗病毒预防仍然存在争议。我们旨在分析接受 DAA 治疗 HCV 感染的慢性或已解决 HBV 感染患者发生 HBV 再激活的绝对风险。
本系统评价和荟萃分析检索了 2010 年 10 月 1 日至 2017 年 9 月 30 日的 PubMed、Ovid MEDLINE、Cochrane 对照试验中心注册库和 Web of Science，以确定在基线时患有慢性或已解决 HBV 感染且接受 DAA 治疗慢性 HCV 感染的患者的研究。还检查了会议记录、摘要集和相关综述的参考文献，以确定潜在的研究。两名独立研究人员提取数据并评估了质量和偏倚风险。使用随机效应模型汇总数据。主要结局是通过标准化命名法定义的 HBV 再激活。本研究已在 PROSPERO 注册，编号为 CRD42017065882。
我们确定了 17 项观察性研究，共纳入 1621 例慢性（n=242）或已解决（n=1379）HBV 感染患者，接受了不同的 DAA 治疗。慢性 HBV 感染患者中 HBV 再激活的患者比例为 24%（95%CI 19-30），已解决 HBV 感染患者为 1.4%（0.8-2.4）。在慢性 HBV 感染患者中，HBV 再激活相关肝炎的患者比例为 9%（95%CI 5-16），且基线时 HBV DNA 低于定量下限的患者与 HBV DNA 可检测的患者相比，HBV 再激活相关肝炎的相对风险（RR）显著降低（RR 0.17，95%CI 0.06-0.50；p=0.0011）。报告了与慢性 HBV 感染患者 HBV 再激活相关的三种主要临床事件（一名患者发生肝功能失代偿，两名患者发生肝功能衰竭，其中一名患者需要进行肝移植）。在已解决 HBV 感染患者中，未报告 HBV 再激活相关肝炎。
DAA 治疗慢性 HBV 和 HCV 合并感染的患者中，HBV 再激活频繁发生，但在已解决 HBV 感染患者中则很少见。对于乙型肝炎表面抗原（HBsAg）检测阳性的患者，特别是 HBV DNA 可检测的患者，使用抗病毒预防可能是必要的。
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