恩替卡韦预防直接作用抗病毒药物治疗 HCV/HBV 双重感染时的 HBV 再激活：一项随机试验。

Entecavir Prevents HBV Reactivation During Direct Acting Antivirals for HCV/HBV Dual Infection: A Randomized Trial.

机构信息

Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Department of Internal Medicine and Hepatitis Research Center, National Taiwan University Hospital; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.

出版信息

Clin Gastroenterol Hepatol. 2022 Dec;20(12):2800-2808. doi: 10.1016/j.cgh.2021.11.032. Epub 2021 Dec 2.

DOI:10.1016/j.cgh.2021.11.032

PMID:34864158

Abstract

BACKGROUND & AIMS: A strategy to prevent hepatitis B virus (HBV) virologic reactivation (HBVr) and clinical reactivation (CR) during direct acting antiviral (DAA) treatment of hepatitis C virus (HCV)/HBV dual infection remains an unresolved issue.

METHODS

Noncirrhotic patients with dual HCV/HBV infection were enrolled and allocated randomly to 1 of 3 groups as follows: 12 weeks of DAA alone (group 1), 12 weeks of DAA plus 12 weeks of entecavir (group 2), or 12 weeks of DAA plus 24 weeks of entecavir (group 3). The entire study duration was 72 weeks. The primary end point was the occurrence of HBVr (defined by an increase of HBV DNA level >10-fold with quantifiable HBV DNA at baseline or the presence of HBV DNA with prior unquantifiable HBV DNA) and CR (defined by serum alanine aminotransferase level >2-fold the upper limit of normal in addition to HBVr).

RESULTS

Fifty-six patients were allocated randomly as follows: 20 patients in group 1, 16 patients in group 2, and 20 patients in group 3. In group 1, HBV DNA levels increased significantly as early as 4 weeks after initiation of DAA and persisted until the end of the study. During DAA treatment, HBVr occurred in 50% in group 1 vs 0% in group 2 and 0% in group 3 (P < .001), whereas the majority of HBVr in groups 2 and 3 occurred 12 weeks after cessation of entecavir (cumulative incidence, 93.8% in group 2 and 94.7% in group 3). Three patients (5.4%; 1 in each group) showed CR at week 48 and did not receive entecavir treatment.

CONCLUSIONS

Twelve weeks of entecavir is suggested to be co-administered with DAA for HCV/HBV dually infected patients.

CLINICALTRIALS

gov no: NCT04405011.

摘要

背景与目的

在直接作用抗病毒（DAA）治疗丙型肝炎病毒（HCV）/乙型肝炎病毒（HBV）双重感染期间，预防乙型肝炎病毒（HBV）病毒学再激活（HBVr）和临床再激活（CR）的策略仍然是一个未解决的问题。

方法

本研究纳入了非肝硬化的双重 HCV/HBV 感染患者，并随机分为以下 3 组中的 1 组：单用 DAA 12 周（第 1 组）、DAA 联合恩替卡韦 12 周（第 2 组）或 DAA 联合恩替卡韦 24 周（第 3 组）。整个研究持续 72 周。主要终点是 HBVr（定义为基线时 HBV DNA 水平增加 10 倍以上且基线时有可量化的 HBV DNA，或 HBV DNA 之前不可量化而现在有可量化的 HBV DNA）和 CR（定义为血清丙氨酸氨基转移酶水平高于正常上限 2 倍以上，同时存在 HBVr）的发生。

结果

56 例患者随机分配如下：第 1 组 20 例，第 2 组 16 例，第 3 组 20 例。第 1 组患者在 DAA 开始后 4 周内 HBV DNA 水平显著升高，并持续至研究结束。在 DAA 治疗期间，第 1 组 HBVr 发生率为 50%，而第 2 组和第 3 组均为 0%（P<.001），而第 2 组和第 3 组的大多数 HBVr 发生在恩替卡韦停药后 12 周（累积发生率，第 2 组为 93.8%，第 3 组为 94.7%）。3 例患者（5.4%；每组 1 例）在第 48 周出现 CR，未接受恩替卡韦治疗。