Absence of interferon-lambda 4 enhances spontaneous clearance of acute hepatitis C virus genotypes 1-3 infection
Artikel i vetenskaplig tidskrift, 2021

Objectives Absence of a functional interferon-lambda 4 (IFN-lambda 4) 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-lambda 4 was absent (44% vs. 20% for IFNL4 TT/TTrs1368234815 and Delta G(rs1368234815) respectively, p < .001; OR 3.2) across genotypes 1-3. The proportion lacking IFN-lambda 4 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-lambda 4, reduced ITPase activity markedly augmented the likelihood of resolution (65% vs. 29% for <100% and 100% ITPase activity, p = .006). Conclusions Absence of IFN-lambda 4 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-lambda 4, reduced ITPase activity improved outcome.

HCV

spontaneous resolution

Interferon-λ 4

spontaneous clearance

hepatitis C virus

incident infection

inosine triphosphate pyrophosphatase

acute infection

IFN-λ4

ITPA

Författare

Jesper Waldenstrom

Göteborgs universitet

Sahlgrenska universitetssjukhuset

Martin Kaberg

Karolinska Institutet

Marianne Alanko Blome

Lunds universitet

Anders Widell

Lunds universitet

Per Bjorkman

Lunds universitet

Staffan Nilsson

Chalmers, Matematiska vetenskaper, Tillämpad matematik och statistik

Göteborgs universitet

Anders Hammarberg

Karolinska Institutet

Stockholms läns landsting

Ola Weiland

Karolinska Institutet

Kristina Nystrom

Sahlgrenska universitetssjukhuset

Göteborgs universitet

Martin Lagging

Sahlgrenska universitetssjukhuset

Göteborgs universitet

Scandinavian Journal of Gastroenterology

0036-5521 (ISSN) 1502-7708 (eISSN)

Vol. In Press

Ämneskategorier

Infektionsmedicin

Gastroenterologi

Mikrobiologi inom det medicinska området

DOI

10.1080/00365521.2021.1925956

PubMed

34034600

Mer information

Senast uppdaterat

2021-06-07