Department of Infectious Diseases/Virology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Infectious Diseases, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.
Scand J Gastroenterol. 2021 Jul;56(7):855-861. doi: 10.1080/00365521.2021.1925956. Epub 2021 May 25.
Absence of a functional interferon-λ 4 (IFN-λ4) gene () predicts spontaneous resolution of acute hepatitis C virus (HCV) infections in regions with a predominance of genotype 1, whereas variants of the inosine triphosphate pyrophosphatase (ITPase) gene () entailing reduced activity associate with increased sustained virologic response rates following some therapeutic regimens. This study aimed at investigating the impact of on acute HCV genotype 2 or 3 infections, and whether ITPase activity influenced outcome.
Two hundred and seven people who injected drugs (PWID) with documented anti-HCV seroconversion, and 57 PWID with reinfection with HCV were analyzed regarding (rs368234815 and rs12979860) and (rs1127354 and rs7270101), and longitudinally followed regarding HCV RNA.
The spontaneous clearance of HCV infection in anti-HCV seronegative PWID was enhanced when IFN-λ4 was absent (44% vs. 20% for TT/TT and ΔG respectively, < .001; OR 3.2) across genotypes 1-3. The proportion lacking IFN-λ4 was further increased following resolution of repeated re-exposure to HCV (74% among re-infected participants who had cleared at least two documented HCV infections). genetic variants did not independently impact on the outcome, but among males lacking IFN-λ4, reduced ITPase activity markedly augmented the likelihood of resolution (65% vs. 29% for <100% and 100% ITPase activity, = .006).
Absence of IFN-λ4 entails an enhanced likelihood of spontaneous resolution both following primary acute infection and repeated re-exposure to HCV across genotypes 1-3. Among men lacking IFN-λ4, reduced ITPase activity improved outcome.
干扰素-λ 4 (IFN-λ4) 基因无功能 () 预测在以基因型 1 为主的地区，急性丙型肝炎病毒 (HCV) 感染的自发缓解，而三磷酸鸟苷焦磷酸酶 (ITPase) 基因的 () 变异导致活性降低与某些治疗方案后的持续病毒学应答率增加有关。本研究旨在调查在急性 HCV 基因型 2 或 3 感染中 的影响，以及 ITPase 活性是否影响结局。
对 207 名有记录的抗 HCV 血清转换的静脉注射吸毒者 (PWID) 和 57 名 HCV 再次感染的 PWID 进行了分析，以确定 (rs368234815 和 rs12979860) 和 (rs1127354 和 rs7270101)，并对 HCV RNA 进行了纵向随访。
在抗 HCV 血清阴性的 PWID 中，当 IFN-λ4 缺失时，HCV 感染的自发清除得到增强 (TT/TT 和 ΔG 分别为 44%和 20%， < .001；OR 3.2)，跨越基因型 1-3。在再次暴露于 HCV 后至少两次有记录的 HCV 感染得到清除的再感染参与者中，缺失 IFN-λ4 的比例进一步增加 (74%)。 基因变异不能独立影响结局，但在缺乏 IFN-λ4 的男性中，ITPase 活性降低显著增加了缓解的可能性 (65%比 <100%和 100% ITPase 活性的 29%， = .006)。
缺乏 IFN-λ4 可增强原发性急性感染和再次暴露于基因型 1-3 的 HCV 后自发缓解的可能性。在缺乏 IFN-λ4 的男性中，ITPase 活性降低改善了结局。
