Absence of interferon-λ 4 enhances spontaneous clearance of acute hepatitis C virus genotypes 1-3 infection. (3rd July 2021)

• Record Type: Journal Article
• Authors: Waldenström, Jesper; Kåberg, Martin; Alanko Blomé, Marianne; Widell, Anders; Björkman, Per; Nilsson, Staffan; Hammarberg, Anders; Weiland, Ola; Nyström, Kristina; Lagging, Martin
• Is Part Of: Scandinavian journal of gastroenterology. Volume 56:Number 7(2021)
• Page Start: 855
• Page End: 861
• Publication Date: 2021-07-03
• Subjects: Interferon-λ 4 -- IFN-λ4 -- inosine triphosphate pyrophosphatase -- ITPA -- hepatitis C virus -- HCV -- acute infection -- incident infection -- spontaneous clearance -- spontaneous resolution; Gastroenterology -- Periodicals; Digestive organs -- Diseases -- Periodicals; 616.33
• DOI: 10.1080/00365521.2021.1925956
• Languages: English
• ISSNs: 0036-5521

Abstract

Abstract: Objectives: Absence of a functional interferon-λ 4 (IFN-λ4) gene ( IFNL4 ) 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 ( ITPA ) entailing reduced activity associate with increased sustained virologic response rates following some therapeutic regimens. This study aimed at investigating the impact of IFNL4 on acute HCV genotype 2 or 3 infections, and whether ITPase activity influenced outcome. Materials and Methods: Two hundred and seven people who injected drugs (PWID) with documented anti-HCV seroconversion, and 57 PWID with reinfection with HCV were analyzed regarding IFNL4 (rs368234815 and rs12979860) and ITPA (rs1127354 and rs7270101), and longitudinally followed regarding HCV RNA. Results: The spontaneous clearance of HCV infection in anti-HCV seronegative PWID was enhanced when IFN-λ4 was absent (44% vs. 20% for IFNL4 TT/TTrs1368234815 and ΔGrs1368234815 respectively, p < .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). ITPA 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, p = .006). Conclusions: 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.