IL28B alleles associated with poor hepatitis C virus (HCV) clearance protect against inflammation and fibrosis in patients infected with non-1 HCV genotypes

Abstract

on behalf of the Swiss Hepatitis C Cohort Study Group the ANRS HC EP 26 Genoscan Study GroupGenetic polymorphisms near IL28B are associated with spontaneous and treatmentinduced clearance of hepatitis C virus (HCV), two processes that require the appropriate activation of the host immune responses. Intrahepatic inflammation is believed to mirror such activation, but its relationship with IL28B polymorphisms has yet to be fully appreciated. We analyzed the association of IL28B polymorphisms with histological and followup features in 2335 chronically HCV-infected Caucasian patients. Assessable phenotypes before any antiviral treatment included necroinflammatory activity (n 5 1,098), fibrosis (n 5 1,527), fibrosis progression rate (n 5 1,312), and hepatocellular carcinoma development (n 5 1,915). Associations of alleles with the phenotypes were evaluated by univariate analysis and multivariate logistic regression, accounting for all relevant covariates. The rare G allele at IL28B marker rs8099917-previously shown to be at risk of treatment failure-was associated with lower activity (P 5 0.04), lower fibrosis (P 5 0.02) with a trend toward lower fibrosis progression rate (P 5 0.06). When stratified according to HCV genotype, most significant associations were observed in patients infected with non-1 genotypes (P 5 0.003 for activity, P 5 0.001 for fibrosis, and P 5 0.02 for fibrosis progression rate), where the odds ratio of having necroinflammation or rapid fibrosis progression for patients with IL28B genotypes TG or GG versus TT were 0.48 (95% confidence intervals 0.30-0.78) and 0.56 (0.35-0.92), respectively. IL28B polymorphisms were not predictive of the development of hepatocellular carcinoma. Conclusion: In chronic hepatitis C, IL28B variants associated with poor response to interferon therapy may predict slower fibrosis progression, especially in patients infected with non-1 HCV genotypes. (HEPATOLOGY 2012;55:384-394)

Liver fibrosis progression at autopsy in injecting drug users infected by hepatitis C: A longitudinal long-term cohort study

“…The median fibrosis progression rate of 0.07 per year observed in this cohort was similar to or lower than reported in other studies of patients with chronic HCV-infection [16][17][18][19][20], but the progression rate was higher than in studies of young females who contracted an HCVinfection accidentally as a result of infected anti-D immunoglobulin in Ireland and Germany [5,21]. In a meta-analysis of the stage-specific fibrosis progression rate in different populations of HCV-patients, the mean progression rate among the IDUs were: F0-F1 0.116, F1-F2 0.085, F2-F3 0.085 and F3-F4 0.130 [20].…”

Deep-Sequencing Analysis of the Association between the Quasispecies Nature of the Hepatitis C Virus Core Region and Disease Progression

“…Interestingly, in contrast to the core region, consensus has not been reached as to the relationship between disease progression and the IL28B SNP, which is associated with IFN resistance (14)(15)(16)(17). Previously, we reported that there was no correlation between the onset of HCC and the IL28B SNP (9).…”

IL28B SNPs rs12979860 and rs8099917 Are Associated with Inflammatory Response in Argentine Chronic HCV Patients

“…The role of these SNPs in the host inflammatory response and evolution of chronic infection in untreated chronic HCV patients is not well understood. Recent studies yielded contradictory results and have shown rs12979860 CC (or rs8099917 TT) association with more advanced fibrosis or cirrhosis [16] [17] and worse clinical outcomes [18], while others have reported rs12979860 TT (or rs8099917 GG) to be associated with more advanced fibrosis or cirrhosis [19] IL28B genotype with fibrosis [22]. The aim of our study was to determine whether SNPs rs12979860 and rs8099917 can be considered a prognostic host factor in untreated chronically HCV-infected patients from an Argentine cohort, by analyzing host haplotypes involved in modulation of patient's immune responses.…”