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

Abstract

Background and AimsRecently, 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.MethodsSeven 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.ResultsCCrs12979860 was more common among HCV genotype 2 or 3 infected treatment-naïve 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.ConclusionThis 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.

Interleukin‐28B polymorphisms and interferon gamma inducible protein‐10 serum levels in seronegative occult hepatitis C virus infection

“…Finally, no relation between IL-28B genotypes and liver enzyme levels or liver fibrosis was found in patients with occult or chronic HCV infection. This is in agreement with previous reports in which no relation was shown between IL-28B genotypes and liver necroinflammation and fibrosis in patients with chronic hepatitis C infected with the HCV 1 genotype [Bochud et al, 2012;Ydreborg et al, 2013], which is the prevalent viral genotype in the patients analyzed in this study (100% in occult and 95% in chronic HCV infection).…”

Prothrombotic genetic risk factors are associated with an increased risk of liver fibrosis in the general population

“…Measuring liver stiffness with TE is an effective, non-invasive, reproducible and currently well-established method to assess liver fibrosis [28,46,47]. Several studies have previously described associations between genetic variants and various liver diseases, using transient elastography as phenotype [48][49][50][51][52][53][54][55][56]. We used a cut-off of 8.0 kPa for clinically relevant liver fibrosis, as proposed and validated in previous community-based studies [26,27].…”

Interleukin‐28B genetic variants in untreated Italian HCV‐infected patients: a multicentre study

“…These findings are well in keeping with those based on liver histology reported in other cohorts , but are in contrast with those reported by Ydreborg et al . on a larger genotype 3 sample size. However, higher proportion of patients IL28BCC and liver stiffness indicating cirrhosis among genotype 3 patients, as compared to 1, was noticed in our cohort.…”