Huang Shang-Chin, Cheng Pin-Nan, Liu Chen-Hua, Yang Hung-Chih, Su Tung-Hung, Tseng Tai-Chung, Chen Pei-Jer, Kao Jia-Horng, Liu Chun-Jen
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan.
Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
J Formos Med Assoc. 2022 May;121(5):920-929. doi: 10.1016/j.jfma.2021.09.002. Epub 2021 Sep 15.
BACKGROUND/PURPOSE: Direct-acting antiviral agents (DAAs) have revolutionized the paradigm for HCV treatment. However, patients with HBV and HCV co-infection receiving DAAs are at significant risk of HBV reactivation, with limited literature addressing the roles of serum chemokines/chemokines. We aimed to explore the profiles and predictive value of serum cytokines/chemokines regarding HBV reactivation in this clinical setting.
From 2017 to 2019, 25 patients with HBV and HCV co-infection scheduled for DAA therapy were prospectively enrolled. At enrolment and after DAA treatment, serial serum cytokine/chemokine levels were examined. The baseline and dynamic levels were compared between those with versus without HBV virologic (defined by an increase of serum HBV DNA to >10 times) and clinical reactivation (defined by > 1.5-fold elevated ALT level than nadir and >100 U/L; or > 2-fold increase from nadir and greater than the upper normal limit, in addition to virologic reactivation).
There were 20 patients (80%) experiencing HBV virologic reactivation and 6 patients (24%) experiencing clinical reactivation. Patients with clinical reactivation had higher pre-treatment TNF-alpha (27.93 versus 18.85 pg/mL, P = 0.015), lower week-4 IFN-gamma (1.07 versus 8.74 pg/mL, P = 0.020) levels and significant declines of CCL2 and TNF-alpha (P < 0.05). Single or combination of these cytokines helped predict clinical reactivation (all P < 0.05).
Higher serum TNF-alpha at baseline and lower IFN-gamma at week 4 were associated with mild clinical reactivation of HBV in patients with HBV/HCV co-infection receiving DAAs. Combination of these cytokines reliably predicted HBV reactivation early.
背景/目的：直接抗病毒药物（DAA）彻底改变了丙型肝炎病毒（HCV）的治疗模式。然而，接受DAA治疗的乙型肝炎病毒（HBV）和HCV合并感染患者存在HBV再激活的重大风险，而关于血清趋化因子/趋化因子作用的文献有限。我们旨在探讨在这种临床环境中血清细胞因子/趋化因子与HBV再激活相关的特征及预测价值。
2017年至2019年，前瞻性纳入25例计划接受DAA治疗的HBV和HCV合并感染患者。在入组时和DAA治疗后，检测系列血清细胞因子/趋化因子水平。比较发生与未发生HBV病毒学再激活（定义为血清HBV DNA增加至>10倍）和临床再激活（定义为ALT水平较最低点升高>1.5倍且>100 U/L；或较最低点升高>2倍且高于正常上限，同时伴有病毒学再激活）患者的基线水平和动态水平。
20例患者（80%）发生HBV病毒学再激活，6例患者（24%）发生临床再激活。发生临床再激活的患者治疗前肿瘤坏死因子-α（TNF-α）水平较高（27.93对18.85 pg/mL，P = 0.015），第4周干扰素-γ（IFN-γ）水平较低（1.07对8.74 pg/mL，P = 0.020），且趋化因子配体2（CCL2）和TNF-α显著下降（P < 0.05）。这些细胞因子单独或联合使用有助于预测临床再激活（均P < 0.05）。
在接受DAA治疗的HBV/HCV合并感染患者中，基线血清TNF-α水平较高和第4周IFN-γ水平较低与HBV轻度临床再激活相关。这些细胞因子联合使用可早期可靠地预测HBV再激活。
