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

Artikel i vetenskaplig tidskrift
Författare Magdalena Ydreborg
Johan Westin
Karolina Rembeck
Magnus Lindh
H. Norrgren
A. Holmberg
Rune Wejstål
Gunnar Norkrans
K. Cardell
O. Weiland
Martin Lagging
Publicerad i Plos One
Volym 8
Nummer/häfte 11
Sidor e80172
ISSN 1932-6203
Publiceringsår 2013
Publicerad vid Institutionen för biomedicin, avdelningen för infektionssjukdomar
Sidor e80172
Språk en
Länkar dx.doi.org/10.1371/journal.pone.008...
Ämnesord 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
Ämneskategorier Infektionsmedicin, Medicinsk genetik

Sammanfattning

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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