Impact of Il28b-related single nucleotide polymorphisms on liver transient elastography in chronic hepatitis C infection.
OBJECTIVE
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® in the context of a real-life trial had samples available for IL28B genotyping (rs12979860) and HCV genotyping.


RESULTS
CC(rs12979860) was more common among HCV genotype 2 or 3 infected treatment-naïve patients than among those infected with genotype 1 (P<0.0001). Additionally CC(rs12979860) 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, CC(rs12979860) was significantly associated with higher viral load (P = 0.001), with a similar non-significant trend noted among HCV genotype 3 infected patients.


CONCLUSIONS
This study confirms previous reports that the CC(rs12979860) 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.
Department of Infectious Diseases/Virology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
Magdalena
M
Ydreborg
Johan
J
Westin
Karolina
K
Rembeck
Magnus
M
Lindh
Hans
H
Norrgren
Anna
A
Holmberg
Rune
R
Wejstål
Gunnar
G
Norkrans
Kristina
K
Cardell
Ola
O
Weiland
Martin
M
Lagging
D000328:Adult; D000483:Alleles; D054459:Elasticity Imaging Techniques; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D008103:Liver Cirrhosis / Q000209:etiology / Q000235:genetics* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D058889:Molecular Typing; D020641:Polymorphism, Single Nucleotide; D019562:Viral Load; D000095022:Interferon Lambda
D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda