Park Young Joo, Yi Ki Youn, Woo Hyun Young, Heo Jeong, Song Geun Am
Department of Internal Medicine, College of Medicine, Pusan National University and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea.
PLoS One. 2025 May 30;20(5):e0324019. doi: 10.1371/journal.pone.0324019. eCollection 2025.
Hepatitis B virus (HBV) reactivation in patients with HBV/hepatitis C virus (HCV) co-infection due to direct-acting antiviral agent (DAA) therapy is a growing concern. This study focused on 47 patients with chronic hepatitis C (CHC) and positivity for HBV surface antigen (HBsAg) who were treated with interferon (IFN)-based therapy, DAA, or DAA after IFN-based therapy failure and followed for a median of 53 months. Here, we aimed to determine HBV reactivation rates and associated factors, the incidence of HBV and liver-related events, and the rate of sustained virologic response (SVR) for HCV. Fifteen (15/47, 31.9%) patients experienced HBV reactivation during or after HCV treatment. This reactivation occurred significantly more frequently in patients who received DAA treatment after IFN-based treatment failure than in those who received IFN-based treatment (IFN-based vs. DAA vs. DAA treatment after IFN-based treatment failure 11.8% vs. 35.3% vs. 53.8%, respectively; p = 0.046). The interval from HCV treatment initiation to HBV reactivation was shortest in the DAA group (4.2 months), followed by the DAA after IFN-based treatment failure group (6.4 months) and the IFN-based treatment group (44.5 months) (p < 0.001). One case of HBV-related hepatitis spontaneously resolved after 4 weeks. The rate of SVR for the entire cohort was 87.2%, with no significant difference in this regard among the IFN-based treated, DAA-treated, and DAA-treated after IFN-based treatment failure arms at 82.4%, 88.2%, and 92.3%, respectively. HBV reactivation in HBsAg-positive CHC patients is more common and occurs earlier in those who receive DAA treatment after IFN-based treatment failure than in those with IFN-based treatment. Therefore, all patients with CHC should be tested for HBV exposure prior to DAA treatment. In addition, HBsAg positive patients, especially those among whom have previously experienced IFN-based treatment failure, should be closely monitored for HBV reactivation during DAA therapy.
由于直接抗病毒药物（DAA）治疗导致乙肝病毒（HBV）/丙肝病毒（HCV）合并感染患者出现HBV再激活的情况日益受到关注。本研究聚焦于47例慢性丙型肝炎（CHC）患者，这些患者乙肝表面抗原（HBsAg）呈阳性，接受了基于干扰素（IFN）的治疗、DAA治疗或在基于IFN的治疗失败后接受DAA治疗，并进行了中位时间为53个月的随访。在此，我们旨在确定HBV再激活率及相关因素、HBV和肝脏相关事件的发生率以及HCV的持续病毒学应答（SVR）率。15例（15/47，31.9%）患者在HCV治疗期间或之后出现HBV再激活。这种再激活在基于IFN的治疗失败后接受DAA治疗的患者中发生频率显著高于接受基于IFN治疗的患者（基于IFN治疗组与DAA治疗组与基于IFN治疗失败后DAA治疗组分别为11.8% vs. 35.3% vs. 53.8%；p = 0.046）。从HCV治疗开始到HBV再激活的间隔时间在DAA组最短（4.2个月），其次是基于IFN治疗失败后DAA治疗组（6.4个月）和基于IFN治疗组（44.5个月）（p < 0.001）。1例HBV相关肝炎在4周后自发缓解。整个队列的SVR率为87.2%，基于IFN治疗组、DAA治疗组和基于IFN治疗失败后DAA治疗组在这方面无显著差异，分别为82.4%、88.2%和92.3%。HBsAg阳性的CHC患者中HBV再激活更为常见，且在基于IFN治疗失败后接受DAA治疗的患者中比接受基于IFN治疗的患者出现得更早。因此，所有CHC患者在接受DAA治疗前都应检测HBV暴露情况。此外，HBsAg阳性患者，尤其是那些曾经历基于IFN治疗失败的患者，在DAA治疗期间应密切监测HBV再激活情况。
