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Impact of IL28B-Related Single Nucleotide Polymorphisms on Liver Transient Elastography in Chronic Hepatitis C Infection

Journal article
Authors Magdalena Ydreborg
Johan Westin
Karolina Rembeck
Magnus Lindh
H. Norrgren
A. Holmberg
Rune Wejstål
Gunnar Norkrans
K. Cardell
O. Weiland
Martin Lagging
Published in Plos One
Volume 8
Issue 11
Pages e80172
ISSN 1932-6203
Publication year 2013
Published at Institute of Biomedicine, Department of Infectious Medicine
Pages e80172
Language en
Links dx.doi.org/10.1371/journal.pone.008...
Keywords INSULIN-RECEPTOR SUBSTRATE-1, GENOME-WIDE ASSOCIATION, VIRUS GENOTYPE 2, GENETIC-VARIATION, PEGINTERFERON ALPHA-2A, VIROLOGICAL RESPONSE, INTERFERON-ALPHA, VIRAL KINETICS, PLUS RIBAVIRIN, UP-REGULATION
Subject categories Infectious Medicine, Medical Genetics

Abstract

Background and Aims: Recently, several genome-wide association studies have revealed that single nucleotide polymorphisms (SNPs) in proximity to IL28B predict spontaneous clearance of hepatitis C virus (HCV) infection as well as outcome following pegylated interferon and ribavirin therapy among genotype 1 infected patients. Additionally the presence of the otherwise favorable IL28B genetic variants in the context of HCV genotype 3 infection reportedly entail more pronounced liver fibrosis and steatosis. The present study aimed to evaluate the impact of IL28B SNP variability on liver stiffness as accessed by transient elastography. Methods: Seven hundred and seventy-one Swedish HCV infected patients sequentially undergoing liver stiffness measurement by means of Fibroscan (R) in the context of a real-life trial had samples available for IL28B genotyping (rs12979860) and HCV genotyping. Results: CCrs12979860 was more common among HCV genotype 2 or 3 infected treatment-naive patients than among those infected with genotype 1 (P<0.0001). Additionally CCrs12979860 among HCV genotype 3 infected patients was associated with higher liver stiffness values (P = 0.004), and higher AST to platelet ratio index (APRI; p = 0.02) as compared to carriers of the T allele. Among HCV genotype 1 infected patients, CCrs12979860 was significantly associated with higher viral load (P = 0.001), with a similar non-significant trend noted among HCV genotype 3 infected patients. Conclusion: This study confirms previous reports that the CCrs12979860 SNP is associated with more pronounced liver pathology in patients chronically infected with HCV genotype 3 as compared to genotype 1, suggesting that IL28B genetic variants differently regulates the course of HCV infection across HCV genotypes.

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