Abstract

BackgroundSeveral genes and their single nucleotide polymorphisms (SNPs) are associated with either spontaneous resolution of hepatitis C infection or better treatment-induced viral clearance. We tested a cohort of intravenous drug users (IVDU) diagnosed with chronic hepatitis C virus (HCV) for treatment response and its association with the SNPs in the interleukin-6 (rs1800795-IL6) and the interleukin-28B (rs12979860-IL28B) genes.MethodsThe study included 110 Croatian IVDU positive for anti-HCV antibody. Genotyping was performed by polymerase chain reaction (PCR) based approach. Patients were treated by standard pegylated-interferon/ribavirin and followed throughout a period of four years, during which sustained virological response (SVR) was determined. All data were analysed with statistical package SPSS 19.0 (IBM Corp, Armonk, NY, USA) and PLINK v1.07 software.ResultsPatients showed a significantly better response to treatment according to the number of copies of the C allele carried at rs1800795-IL6 (P = 0.034). All but one of the patients with CC genotype achieved SVR (93%), whereas the response rate of patients with GG genotype was 64%. The association of rs1800795-IL6 with SVR status remained significant after further adjustment for patients’ age, fibrosis staging, and viral genotype (OR 2.15, 95% CI 1.16–4.68, P = 0.019). Distributions of allele frequencies at the locus rs12979860-IL28B among the study cohort and the underlying general population were suggestive of a protective effect of CC genotype in acquiring chronic hepatitis C in the Croatian IVDU population.DiscussionThe rs1800795-IL6 polymorphism is associated with positive response to treatment in IVDU patients positive for HCV infection. A protective role of rs12979860-IL28B CC genotype in acquiring chronic hepatitis C is suggested for Croatian IVDU population.

Highlights

  • It is estimated that chronic hepatitis C virus (HCV) infection affects nearly 170 million individuals worldwide (Averhoff, Glass & Holtzman, 2012; World Health Organization, 2014)

  • We studied whether interleukin-28B or interleukin-6 (IL-6) promoter single nucleotide polymorphisms (SNPs) affects the response to the PegIFN-a2a/ribavirin antiviral treatment in intravenous drug users (IVDU) patients diagnosed with chronic hepatitis C

  • A total of 110 IVDU patients with elevated liver function tests were diagnosed with a chronic hepatitis C, treated by standard interferon 2-alfa/ribavirin protocol and followed over at least one year for a sustained virological response (SVR)

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Summary

Introduction

It is estimated that chronic hepatitis C virus (HCV) infection affects nearly 170 million individuals worldwide (Averhoff, Glass & Holtzman, 2012; World Health Organization, 2014). With three new HCV DAAs approved, IFN-free combinations are reserved for patients with advanced liver disease (fibrosis METAVIR score F3 or F4). Several genes and their single nucleotide polymorphisms (SNPs) are associated with either spontaneous resolution of hepatitis C infection or better treatment-induced viral clearance. We tested a cohort of intravenous drug users (IVDU) diagnosed with chronic hepatitis C virus (HCV) for treatment response and its association with the SNPs in the interleukin-6 (rs1800795-IL6) and the interleukin-28B (rs12979860-IL28B) genes. Distributions of allele frequencies at the locus rs12979860-IL28B among the study cohort and the underlying general population were suggestive of a protective effect of CC genotype in acquiring chronic hepatitis C in the Croatian IVDU population. A protective role of rs12979860-IL28B CC genotype in acquiring chronic hepatitis C is suggested for Croatian IVDU population

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