Elsevier

Journal of Hepatology

Volume 56, Issue 3, March 2012, Pages 527-532
Journal of Hepatology

Research Article
IL28B polymorphism is associated with treatment response in patients with genotype 4 chronic hepatitis C

https://doi.org/10.1016/j.jhep.2011.09.008Get rights and content

Background & Aims

Polymorphisms in the region of the interleukin (IL)28B gene have been associated with pegylated-interferon (PEG-IFN) and ribavirin treatment response mainly in genotype 1 HCV infections. However, there are few data on HCV genotype 4 (HCV-4) infection. We evaluated, in a unique well-characterized cohort of HCV-4 patients, the association of IL28B polymorphism with response to treatment or liver disease severity.

Methods

This study included 164 HCV-4 patients from different ethnic groups (Egyptian, European, and Sub-Saharan African). Among these patients, 82 were studied for response and 160 for disease severity. Free DNA extracted from all the 164 patient’s serum samples was analyzed by direct sequencing of the SNP rs12979860 of IL28B. Genetic and bio-clinical features from patients having sustained virological response (43 SVR patients) and from those who did not respond to treatment or had a relapse after the end of the treatment (39 NR patients) were compared. IL28B polymorphism was compared between the 78 patients with mild fibrosis (Metavir score F0–F1) and the 82 with advanced fibrosis (F2–F4).

Results

Our data showed a better treatment response rate of the C allele of the IL28B gene SNP rs12979860 (p = 0.0008). The response rates were 81.8%, 46.5%, and 29.4% for genotype CC, CT, and TT, respectively. No significant relationship was found between rs12979860 and the severity of the disease.

Conclusions

The SNP rs12979860 is strongly associated with SVR in patients infected with HCV-4, but not with liver disease severity. Analysis of IL28B genotype might be used to guide treatment for these patients.

Introduction

Hepatitis C virus (HCV) is a major cause of chronic liver disease, with more than 170 million infected individuals worldwide. Genotype 4 (HCV-4) is the most frequent cause of chronic hepatitis C in the Middle-East, and sub-Saharan Africa. It has recently spread to Southern Europe, particularly among intravenous drug users and in immigrants [1], [2]. HCV-4 is mainly found in Egypt, the country with the highest prevalence of HCV worldwide (15%), where HCV-4 represents 90% of all HCV cases. For genotype 4 infected patients, the most effective therapy to eradicate the virus consists of a combination of pegylated interferon (PEG-IFN) alpha and ribavirin. Unfortunately, the rate of sustained virological response (SVR) is around 50% in genotype 1 and 4 infected patients [1], [2], [3], [4], [5]. Because a significant number of patients will fail to respond or will have significant side effects, it is of major interest for both patient care and economic approach to predict non response [6], [7]. The sequencing of the human genome, together with the development of high-throughput technologies delivering fast, affordable and accurate genomic information, represent a unique opportunity to predict treatment response. Several independent genome-wide association studies (GWAS) reported single nucleotide polymorphisms (SNPs) near the IL28B (IFN-λ3) locus that displayed association with treatment response, mainly in genotype 1 infected patients [8], [9], [10], [11], [12].

Interestingly, the association between IL28B polymorphism and SVR was not confirmed in other cohorts of genotypes 2 and 3 infected patients. In a cohort of 281 patients infected with HCV genotype 3, there was no association of SNP rs12979860 with SVR to PEG-IFN/ribavirin therapy [13]. Also, the association of rs12979860 with an SVR in patients infected with genotype 2/3 HCV was present only in those who did not achieve a rapid virological response (RVR) [14]. Furthermore, in 482 Asian HCV-2 patients treated with the standard of care (SOC) (PEG-IFN plus ribavirin), the rs8099917 polymorphism (near the IL28B gene) played no role in achieving SVR with or without RVR [15].

The majority of studies focused on genotypes 1, 2 and 3. There is few data so far regarding the role of IL28B polymorphism in HCV-4 patients with respect to response to antiviral therapy or fibrosis progression [12], [16]. The aim of this study was to investigate, in a well-characterized unique large cohort of HCV-4 patients, the effect of IL28B rs12979860 polymorphism on response to treatment and severity of the disease.

Section snippets

Patients and samples

This cohort was composed of consecutive patients with genotype 4 chronic hepatitis C who were followed-up at Beaujon Hospital (Clichy, France). One-hundred and sixty-four patients with an established diagnosis of HCV-4 chronic hepatitis with detectable anti-HCV antibodies, and detectable serum HCV RNA were included in this study.

A percutaneous liver biopsy was performed in 160 patients and a METAVIR score was allocated [17].

Eighty-two patients were included in the response cohort if they met

Patients

A total of 164 HCV-4 infected patients, 43 (26%) women, and 121 (74%) men, were studied. Baseline characteristics of these 164 patients are presented in Table 1. The median age at onset of therapy was 44 years old [range: 22–66]. This study recruited patients from three different ethnic groups (as self-reported by the patient) with 70 (43%) Egyptians, 53 (32%) Europeans, and 37 (23%) Sub-Saharan Africans. A liver biopsy was performed in 160 of them who were included in a severity analysis.

Discussion

This unique cohort in HCV-4 infected populations has allowed us to analyze relationship between rs12979860 and treatment response or fibrosis stage, not evaluated previously. This study was performed in a large unique mono-centric cohort of 164 patients with HCV-4 infection. In this cohort, three different ethnic groups were represented with 70 (43%) Egyptians, 53 (32%) Europeans, and 37 (23%) Sub-Saharan Africans. This unique ethnic population has not yet been evaluated for relationship

Contribution

T.A.: study concept and design; acquisition of data; analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content; statistical analysis, technical, or material support; study supervision. P.B.: statistical analysis, critical revision of the manuscript. S.D.M., J.M.P., M.B., I.B., Q.Z., M.P.R., D.V., M.V., M.L., M.M.P., O.L., E.E., N.B., P.B., D.V., A.E.R., P.M.: acquisition of data; technical support, critical revision

Conflict of interest

The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.

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    The abstract of this study was submitted before April 7th, 2011 to the 18th Annual International Symposium of Hepatitis C Virus and Related Viruses (September 2011, Seattle, USA).

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