Relation of IL28B Gene Polymorphism with Biochemical and Histological Features in Hepatitis C Virus-Induced Liver Disease

José A Agúndez,Luis Ortega,Manuel Díaz-Rubio,Marta Vidaurreta,Gabriela Díaz-Zelaya,Francisca Cuenca,Carmen Martínez,María L Maestro,Marta Agreda,Elena García-Martin,Miguel Carballo,José M Ladero,Avelina Suárez,Gulam Waris

doi:10.1371/journal.pone.0037998

Abstract

Background/AimsPolymorphism at the IL28B gene may modify the course of hepatitis C virus (HCV) chronic infection. Our aim was to study the influence of IL28B rs12979860 gene polymorphism on the biochemistry and pathology of HCV-induced disease in the clinical course from mild chronic hepatitis C to hepatocellular carcinoma.MethodsWe have determined the rs12979860 single nucleotide polymorphism (SNP) upstream IL28B gene in two groups of patients with HCV-induced chronic liver disease: 1) 268 patients (159 men) with biopsy-proven chronic hepatitis C, to analyse its relation with biochemical, virological and histological features; and 2) 134 patients (97 men) with HCV-related hepatocellular carcinoma. The distribution of the analysed SNP in hepatocellular carcinoma patients was compared with that found in untreated chronic hepatitis C patients. All patients were white and most were Spaniards.ResultsIn multivariate analysis ALT values were higher (P = 0.001) and GGT values were lower (P<0.001) in chronic hepatitis C patients homozygotes for the major rs12979860C allele as compared with carriers of the mutated rs12979860T allele. Steatosis was more frequent (Odds ratio = 1.764, 95% C.I. 1.053–2.955) and severe (P = 0.026) in carriers of the rs12979860T allele. No relation was found between the analysed SNP and METAVIR scores for necroinflammation and fibrosis, and there were no differences in the distribution of the analysed SNP between hepatocellular carcinoma and untreated chronic hepatitis C patients.ConclusionThe IL28B rs12979860 polymorphism correlates with the biochemical activity and the presence and severity of liver steatosis in chronic hepatitis C.

Highlights

The natural history of the infection with hepatitis C virus (HCV) is variable and difficult to define
Long-term follow up studies in patients with chronic hepatitis C have shown a great variability in the rate of progression of the liver disease, after 2 or more decades many infected persons develop progressive hepatic fibrosis and cirrhosis, that is related to a high risk of suffering from hepatocellular carcinoma (HCC)
The aim of this study was to investigate the distribution of the rs12979860 single nucleotide polymorphism (SNP) upstream of the IL28B gene in a wellphenotyped population of chronically HCV-infected patients covering the whole spectrum of disease severity, from null-mild fibrosis to hepatocellular carcinoma, to elucidate whether this polymorphic trait may be related with the course of chronic HCV infection

Summary

Introduction

The natural history of the infection with hepatitis C virus (HCV) is variable and difficult to define. Long-term follow up studies in patients with chronic hepatitis C have shown a great variability in the rate of progression of the liver disease, after 2 or more decades many infected persons develop progressive hepatic fibrosis and cirrhosis, that is related to a high risk of suffering from hepatocellular carcinoma (HCC). There are some reports on host genetic factors related to the risk of acute HCV infection becoming chronic [6] and to the rate of progression in the chronic phase, as are some human leukocyte antigen class II antigens [7,8] and polymorphisms in the genes of transforming growth factor-b1 [9] and angiotensin II [10]

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