Elsevier

Journal of Clinical Virology

Volume 58, Issue 1, September 2013, Pages 254-257
Journal of Clinical Virology

Short communication
The influence of single and combined IL28B polymorphisms on response to treatment of chronic hepatitis C

https://doi.org/10.1016/j.jcv.2013.06.014Get rights and content

Abstract

Background

Three single nucleotide polymorphisms (SNPs) near IL28B gene were shown to be highly predictive of sustained virological response (SVR) in patients with chronic hepatitis C virus (HCV) infection.

Objectives

This study attempted to demonstrate the role of single and combined IL28B polymorphisms (rs8099917, rs12979860 and rs12980275) and other host and viral factors in predicting response to treatment, in Caucasian patients infected with HCV genotype 1.

Study design

The IL28B genotypes at 3 SNPs were determined in 106 patients who underwent standard 48-week therapy and out of which 55.7% achieved SVR.

Results

Patients carrying genotypes CCrs12979860 or AArs12980275 were 3.5 and 3 times more likely to achieve SVR, respectively. Genotypes GGrs8099917 and TTrs12979860 were identified as predictors of treatment failure. The presence of IL28B profiles including at least one of the favourable genotypes was identified as the most important factor associated with SVR, followed by younger age and lower grade of histological activity. Of all patients who achieved SVR, 88.1% was carrying one of these IL28B profiles. The strongest PPV of single SNPs for achieving SVR was observed for CCrs12979860 (76.9%). The presence of GGrs8099917 showed the strongest NPV of 85.7%. The correlation of SNPs with other host and viral factors revealed association of TTrs8099917 and lower AST levels.

Conclusions

Results of this study confirm that all investigated IL28B polymorphisms are associated with treatment response and that presence of any of the favourable IL28B genotypes can be considered independent pretreatment determinant of the effectiveness of therapy.

Section snippets

Background

Chronic infection with hepatitis C virus (HCV) is a global health problem, affecting approximately 175 million individuals, worldwide [1]. Currently, the most effective therapy for viral clearance in chronically infected patients is the combination of pegilated interferon-alpha (PEG-IFN-α) and ribavirin (RBV) [2]. The goal of treatment is viral eradication i.e. sustained virological response (SVR), defined as the absence of virus 24 weeks after treatment completion. However, current

Objectives

The aim of this study was to determine the strongest contribution of factors, including IL28B polymorphisms (rs8099917, rs12979860 and rs12980275), their combinations and other host and viral factors in predicting response to therapy among Caucasian patients infected chronically with HCV genotype 1.

Patient population

The study comprised 106 patients with chronic hepatitis C, treated at the Clinics of Infectious and Tropical Diseases, Clinical Center of Serbia and Department of Gastroenterology and Hepatology, Clinical Center “Zvezdara” in Belgrade.

All the patients were of Caucasian origin and infected with HCV genotype 1. They underwent standard antiviral therapy with combination of PEG-IFN-α and ribavirin for 48 weeks [3], [8]. HCV RNA levels were determined at baseline, week 12, at the end of treatment,

Results

In 24-week follow-up after therapy, 55.7% of patients were found to achieve SVR.

Statistical significance confirmed that younger age, lower stage of fibrosis (F0–F2) and particularly lower grade of histological activity (0–2) were associated with favourable treatment outcome (Table 2.). Genotype distributions at all 3 SNP positions were in accordance with Hardy–Weinberg equilibrium but only moderate linkage disequilibrium between SNPs was observed. All 8 possible haplotypes were present with

Discussion

The mechanism by which IL28B variation influences the efficiency of PEG-IFNα/RBV treatment remains unknown. It is also still unclear whether several IL28B SNPs are functional or whether the impact is restricted to one of them.

The frequency of CC genotype in this study (24.5%) was similar to frequencies reported by two other studies −26% [11] and 24.3% [12], one of them including patients from neighbouring country.

This study confirms previously reported results [7], [13], [14] that more than 2

Funding

The study was funded by Ministry of Education, Science and Technological Development, Republic of Serbia, Grant Number 175073.

Competing interests

None declared.

Ethical approval

Informed written consent for participating in this study was obtained from all patients and the study was approved by Ethics Committee of Faculty of Medicine, University of Belgrade, No. 29/VI-12.

Acknowledgements

The authors thank Prof. Vera Pravica from Immunology Department, Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade for her assistance in establishing the SNPs genotyping assay. For technical assistance in performing the study the authors thank Laboratory Technicians Gabrijela Pavlovic and Marija Jankovic from the Virology Department, Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade.

References (18)

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Cited by (8)

  • IL28B rs12980275 variant as a predictor of sustained virologic response to pegylated-interferon and ribavirin in chronic hepatitis C patients: A systematic review and meta-analysis

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    Studies on other liver disease such as CHB, hepatocellular carcinoma and liver transplantation were also excluded. Finally, 16 articles (19 studies) that investigated the association between rs12980275 AA genotype and SVR of HCV patients with PEG-IFN plus RBV treatment meet the criterion, and they were included in this meta-analysis [11,13,14,19–31] (Fig. 1). Table 1 shows the characteristics of the study included in our analysis.

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    Viral kinetics were analysed as a function of these polymorphisms. Favourable genotypes (CC for rs12979860 and rs8099117 TT for) were associated with more rapid decline of viral load [22–24]. Similar data have already been reported by other teams and appear to be related to lower basal activation of IFN-Stimulated Genes (ISGs) for patients with a favourable IL28B polymorphism [25,26].

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