DAAs治疗HCV感染发生HBV再激活的风险:系统评价及Meta分析
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R512.62 R512.63

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国家自然科学基金项目(82370635)


Risk of HBV reactivation in HCV infection treated with direct-acting antiviral agents: a systematic review and Meta-analysis
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    摘要:

    目的 比较接受直接抗病毒药物(DAAs)治疗的丙型肝炎病毒(HCV)感染患者乙型肝炎病毒(HBV)再激活风险,并评估抗HBV治疗预防HBV再激活的有效性。方法 计算机检索中国知网(CNKI)、万方数据库、PubMed、Embase、Cochrane Library 数据库,纳入自建库至2025年2月13日发表的相关文献。按预设纳入与排除标准筛选文献,提取资料并评估质量。采用Revman 5.4 和 Stata 18.0 软件进行Meta分析,并开展敏感性分析和发表偏倚评估。结果 共纳入32篇文献,包括31篇队列研究和1篇随机对照研究。涉及21 530例HCV感染患者。27项研究报告HCV感染合并HBsAg阳性患者DAAs治疗后的合并HBV再激活发生率为30%(95%CI:16%~45%),24项研究报告HCV感染合并HBsAg阴性、HBcAb阳性患者合并HBV再激活率为0,各研究报道的再激活发生率范围为0~15%。选取14篇文献比较HCV感染合并HBsAg阳性与HCV感染合并HBsAg阴性、HBcAb阳性患者DAAs治疗后HBV再激活的风险,相对危险度(RR)=31.06(95%CI:17.98~53.65)。HCV感染合并HBsAg阳性患者中,HBV DNA<检测下限(LLOQ)组与HBV DNA≥LLOQ组的HBV再激活风险差异无统计学意义(RR=0.75,95%CI:0.52~1.06)。HCV感染合并HBsAg阳性患者中,DAAs治疗同时使用核苷(酸)类似物(NAs)进行预防性抗HBV治疗者,其HBV再激活风险仅为对照组的19%(RR=0.19,95%CI:0.06~0.58)。结论 HCV感染合并HBsAg阳性患者接受DAAs治疗后HBV再激活发生率较高;HCV感染合并HBsAg阴性、HBcAb阳性患者接受DAAs治疗后基于现有数据合并HBV再激活发生率估计值为0,但仍存在个别再激活报告,风险并未完全排除。使用NAs预防性抗HBV治疗可降低HCV感染合并HBsAg阳性患者DAAs治疗的HBV再激活风险。对HCV感染患者实施预防性抗HBV治疗和持续管理,有助于提高DAAs治疗的安全性并优化整体疗效。

    Abstract:

    Objective To compare the risk of hepatitis B virus (HBV) reactivation (HBVr) in hepatitis C virus (HCV)-infected patients receiving direct-acting antiviral agents (DAAs), evaluate the effectiveness of prophylactic anti-HBV treatment in preventing HBVr. Methods Relevant literatures published up to February 13, 2025 were systematically retrieved from China National Knowledge Infrastructure (CNKI), Wanfang Database, PubMed, Embase, and Cochrane Library databases. The literatures were screened according to the established inclusion and exclusion criteria, data were extracted and underwent quality assessment. Revman 5.4 and Stata 18.0 software were used for Meta-analysis, sensitivity analysis, and publication bias assessment. Results A total of 32 studies (31 cohort studies and 1 randomized controlled trial) involving 21 530 HCV-infected patients were included. Twenty-seven studies reported that the incidence of pooled HBVr was 30% (95%CI: 16%-45%) in HCV-infected patients combined with HBsAg-positive after DAAs treatment. Twenty-four studies showed that the pooled HBVr rate was 0 in HCV-infected patients with HBsAg negative but HBcAb-positive. HBVr rates reported in each study ranged from 0 to 15%. Fourteen literatures were chosen to compare the risk of HBVr after DAAs treatment between HCV-infected patients with HBsAg-positive and HCV-infected patients with HBsAg-negative but HBcAb-positive, and the relative risk(RR)=31.06 (95% CI: 17.98-53.65). Among HCV-infected patients with HBsAg-positive, there was no statistically significant difference in the risk of HBVr between the group with HBV DNA < LLOQ (lower limit of quantification) and the group with HBV DNA ≥ LLOQ (RR=0.75, 95% CI: 0.52-1.06). Among HCV-infected patients with HBsAg-positive, the risk of HBVr in patients receiving DAAs treatment combined with nucleoside analogues for prophylactic anti-HBV treatment was only 19% of that in the control group (RR=0.19, 95% CI: 0.06-0.58). Conclusion The HCV-infected patients with HBsAg-positive have a high incidence of HBVr after DAAs treatment. The existing data showed that the estimated value of incidence of pooled HBVr was 0 in HCV-infected patients with HBsAg negative but HBcAb positive after DAAs treatment, yet there were still individual reactivation reports, and the risk was not completely ruled out. The use of nucleoside analogues for prophylactic HBV treatment can reduce the risk of HBVr in HBsAg-positive HCV-infected patients after DAAs treatment. Prophylactic HBV treatment and continuous management of HCV-infected patients are helpful to improve the safety of DAAs treatment and optimize the overall treatment effect.

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陈莹,陈君,钟韵,等. DAAs治疗HCV感染发生HBV再激活的风险:系统评价及Meta分析[J]. 中国感染控制杂志,2026,25(1):32-46. DOI:10.12138/j. issn.1671-9638.20262402.
CHEN Ying, CHEN Jun, ZHONG Yun, et al. Risk of HBV reactivation in HCV infection treated with direct-acting antiviral agents: a systematic review and Meta-analysis[J]. Chin J Infect Control, 2026,25(1):32-46. DOI:10.12138/j. issn.1671-9638.20262402.

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  • 收稿日期:2025-04-25
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  • 在线发布日期: 2026-01-28
  • 出版日期: 2026-01-28