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Absence of interferon-λ 4 enhances spontaneous clearance of acute hepatitis C virus genotypes 1-3 infection

Waldenström, Jesper ; Kåberg, Martin ; Alanko Blomé, Marianne LU ; Widell, Anders LU ; Björkman, Per LU orcid ; Nilsson, Staffan ; Hammarberg, Anders ; Weiland, Ola ; Nyström, Kristina and Lagging, Martin (2021) In Scandinavian Journal of Gastroenterology 56(7). p.855-861
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... (More)

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.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
acute infection, HCV, hepatitis C virus, IFN-λ4, incident infection, inosine triphosphate pyrophosphatase, Interferon-λ 4, ITPA, spontaneous clearance, spontaneous resolution
in
Scandinavian Journal of Gastroenterology
volume
56
issue
7
pages
7 pages
publisher
Taylor & Francis
external identifiers
  • pmid:34034600
  • scopus:85106464985
ISSN
0036-5521
DOI
10.1080/00365521.2021.1925956
language
English
LU publication?
yes
id
75a851ef-5416-412d-b18d-6cac4647b949
date added to LUP
2021-06-11 12:04:39
date last changed
2024-03-23 05:55:54
@article{75a851ef-5416-412d-b18d-6cac4647b949,
  abstract     = {{<p>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/TT<sub>rs1368234815</sub> and ΔG<sub>rs1368234815</sub> respectively, p &lt;.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 &lt;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.</p>}},
  author       = {{Waldenström, Jesper and Kåberg, Martin and Alanko Blomé, Marianne and Widell, Anders and Björkman, Per and Nilsson, Staffan and Hammarberg, Anders and Weiland, Ola and Nyström, Kristina and Lagging, Martin}},
  issn         = {{0036-5521}},
  keywords     = {{acute infection; HCV; hepatitis C virus; IFN-λ4; incident infection; inosine triphosphate pyrophosphatase; Interferon-λ 4; ITPA; spontaneous clearance; spontaneous resolution}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{855--861}},
  publisher    = {{Taylor & Francis}},
  series       = {{Scandinavian Journal of Gastroenterology}},
  title        = {{Absence of interferon-λ 4 enhances spontaneous clearance of acute hepatitis C virus genotypes 1-3 infection}},
  url          = {{http://dx.doi.org/10.1080/00365521.2021.1925956}},
  doi          = {{10.1080/00365521.2021.1925956}},
  volume       = {{56}},
  year         = {{2021}},
}