Interferon lambda 4 genotype and pathway in alcoholic hepatitis

Sidsel Støy; Ewa Terczynska-Dyla; Sanne Skovgård Veidal; Kristoffer Rigbolt; Hendrik Vilstrup; Henning Grønbaek; Rune Hartmann; Thomas D. Sandahl

doi:10.1080/00365521.2021.1874046

Interferon lambda 4 genotype and pathway in alcoholic hepatitis

Sidsel Støy^*, Ewa Terczynska-Dyla, Sanne Skovgård Veidal, Kristoffer Rigbolt, Hendrik Vilstrup, Henning Grønbaek, Rune Hartmann, Thomas D. Sandahl

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Abstract

Objectives: Single nucleotide polymorphisms within the interferon lambda 4 (IFNL4) gene influence liver inflammation and fibrosis in chronic liver disease. We investigated whether this is also the case during acute liver disease, alcoholic hepatitis. We, therefore, related variants within the IFNL4 gene to the clinical course of acute alcoholic hepatitis, and characterized the activation state of the IFN lambda system in these patients. Methods: In this pilot study, 58 patients with alcoholic hepatitis were genotyped for the rs368234815IFNL4 single nucleotide polymorphism (deltaG, deltaG/TT: IFN lambda 4 positive, TT/TT: IFN lambda 4 negative). The genotypes were related to mortality, infection and inflammation and expression of the IFNL receptor 1 and IFN inducible genes were measured in liver and peripheral leukocytes. Results: Amongst the alcoholic hepatitis patients who died, the IFN negative patients live longer after diagnosis, and also the IFN negative patients tended to have an overall short-term survival benefit compared to IFN lambda positive patients (p =.058). The IFN lambda 4 negative patients at diagnosis had fewer circulating monocytes and lower plasma soluble CD163. The patients with alcoholic hepatitis had reduced expression of the IFNL receptor 1in both liver and blood compared with healthy controls. In blood, the expression of IFN stimulated genes was lower than in healthy controls and most so in the patients, who died. Conclusions: The IFN lambda 4 pathway seems involved in the acute disease processes of alcoholic hepatitis and patients without IFN lambda expression seem to have a short-term survival benefit.

Original language	English
Journal	Scandinavian Journal of Gastroenterology
Volume	56
Issue	3
Pages (from-to)	304-311
Number of pages	8
ISSN	0036-5521
DOIs	https://doi.org/10.1080/00365521.2021.1874046
Publication status	Published - Mar 2021

Keywords

Alcoholic hepatitis
interferon
interferon-stimulated genes
monocytes
single nucleotide polymorphisms

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10.1080/00365521.2021.1874046

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title = "Interferon lambda 4 genotype and pathway in alcoholic hepatitis",

abstract = "Objectives: Single nucleotide polymorphisms within the interferon lambda 4 (IFNL4) gene influence liver inflammation and fibrosis in chronic liver disease. We investigated whether this is also the case during acute liver disease, alcoholic hepatitis. We, therefore, related variants within the IFNL4 gene to the clinical course of acute alcoholic hepatitis, and characterized the activation state of the IFN lambda system in these patients. Methods: In this pilot study, 58 patients with alcoholic hepatitis were genotyped for the rs368234815IFNL4 single nucleotide polymorphism (deltaG, deltaG/TT: IFN lambda 4 positive, TT/TT: IFN lambda 4 negative). The genotypes were related to mortality, infection and inflammation and expression of the IFNL receptor 1 and IFN inducible genes were measured in liver and peripheral leukocytes. Results: Amongst the alcoholic hepatitis patients who died, the IFN negative patients live longer after diagnosis, and also the IFN negative patients tended to have an overall short-term survival benefit compared to IFN lambda positive patients (p =.058). The IFN lambda 4 negative patients at diagnosis had fewer circulating monocytes and lower plasma soluble CD163. The patients with alcoholic hepatitis had reduced expression of the IFNL receptor 1in both liver and blood compared with healthy controls. In blood, the expression of IFN stimulated genes was lower than in healthy controls and most so in the patients, who died. Conclusions: The IFN lambda 4 pathway seems involved in the acute disease processes of alcoholic hepatitis and patients without IFN lambda expression seem to have a short-term survival benefit.",

keywords = "Alcoholic hepatitis, interferon, interferon-stimulated genes, monocytes, single nucleotide polymorphisms, Alkoholisk leversygdom, genetik",

author = "Sidsel St{\o}y and Ewa Terczynska-Dyla and Veidal, {Sanne Skovg{\aa}rd} and Kristoffer Rigbolt and Hendrik Vilstrup and Henning Gr{\o}nbaek and Rune Hartmann and Sandahl, {Thomas D.}",

year = "2021",

month = mar,

doi = "10.1080/00365521.2021.1874046",

language = "English",

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pages = "304--311",

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TY - JOUR

T1 - Interferon lambda 4 genotype and pathway in alcoholic hepatitis

AU - Støy, Sidsel

AU - Terczynska-Dyla, Ewa

AU - Veidal, Sanne Skovgård

AU - Rigbolt, Kristoffer

AU - Vilstrup, Hendrik

AU - Grønbaek, Henning

AU - Hartmann, Rune

AU - Sandahl, Thomas D.

PY - 2021/3

Y1 - 2021/3

N2 - Objectives: Single nucleotide polymorphisms within the interferon lambda 4 (IFNL4) gene influence liver inflammation and fibrosis in chronic liver disease. We investigated whether this is also the case during acute liver disease, alcoholic hepatitis. We, therefore, related variants within the IFNL4 gene to the clinical course of acute alcoholic hepatitis, and characterized the activation state of the IFN lambda system in these patients. Methods: In this pilot study, 58 patients with alcoholic hepatitis were genotyped for the rs368234815IFNL4 single nucleotide polymorphism (deltaG, deltaG/TT: IFN lambda 4 positive, TT/TT: IFN lambda 4 negative). The genotypes were related to mortality, infection and inflammation and expression of the IFNL receptor 1 and IFN inducible genes were measured in liver and peripheral leukocytes. Results: Amongst the alcoholic hepatitis patients who died, the IFN negative patients live longer after diagnosis, and also the IFN negative patients tended to have an overall short-term survival benefit compared to IFN lambda positive patients (p =.058). The IFN lambda 4 negative patients at diagnosis had fewer circulating monocytes and lower plasma soluble CD163. The patients with alcoholic hepatitis had reduced expression of the IFNL receptor 1in both liver and blood compared with healthy controls. In blood, the expression of IFN stimulated genes was lower than in healthy controls and most so in the patients, who died. Conclusions: The IFN lambda 4 pathway seems involved in the acute disease processes of alcoholic hepatitis and patients without IFN lambda expression seem to have a short-term survival benefit.

AB - Objectives: Single nucleotide polymorphisms within the interferon lambda 4 (IFNL4) gene influence liver inflammation and fibrosis in chronic liver disease. We investigated whether this is also the case during acute liver disease, alcoholic hepatitis. We, therefore, related variants within the IFNL4 gene to the clinical course of acute alcoholic hepatitis, and characterized the activation state of the IFN lambda system in these patients. Methods: In this pilot study, 58 patients with alcoholic hepatitis were genotyped for the rs368234815IFNL4 single nucleotide polymorphism (deltaG, deltaG/TT: IFN lambda 4 positive, TT/TT: IFN lambda 4 negative). The genotypes were related to mortality, infection and inflammation and expression of the IFNL receptor 1 and IFN inducible genes were measured in liver and peripheral leukocytes. Results: Amongst the alcoholic hepatitis patients who died, the IFN negative patients live longer after diagnosis, and also the IFN negative patients tended to have an overall short-term survival benefit compared to IFN lambda positive patients (p =.058). The IFN lambda 4 negative patients at diagnosis had fewer circulating monocytes and lower plasma soluble CD163. The patients with alcoholic hepatitis had reduced expression of the IFNL receptor 1in both liver and blood compared with healthy controls. In blood, the expression of IFN stimulated genes was lower than in healthy controls and most so in the patients, who died. Conclusions: The IFN lambda 4 pathway seems involved in the acute disease processes of alcoholic hepatitis and patients without IFN lambda expression seem to have a short-term survival benefit.

KW - Alcoholic hepatitis

KW - interferon

KW - interferon-stimulated genes

KW - monocytes

KW - single nucleotide polymorphisms

KW - Alkoholisk leversygdom

KW - genetik

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DO - 10.1080/00365521.2021.1874046

M3 - Journal article

C2 - 33602032

AN - SCOPUS:85101185766

SN - 0036-5521

VL - 56

SP - 304

EP - 311

JO - Scandinavian Journal of Gastroenterology

JF - Scandinavian Journal of Gastroenterology

IS - 3

ER -

Interferon lambda 4 genotype and pathway in alcoholic hepatitis

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