Short communicationThe influence of single and combined IL28B polymorphisms on response to treatment of chronic hepatitis C
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.
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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
2015, Clinics and Research in Hepatology and GastroenterologyCitation Excerpt :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.
Roles of ITPA and IL28B genotypes in chronic Hepatitis C patients treated with peginterferon plus ribavirin in Tunisian population
2015, Journal of Clinical VirologyCitation Excerpt :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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2020, Journal of Medical BiochemistryIL-28B genotypes as predictors of long-term outcome in patients with hepatitis C-related severe liver injury
2019, Journal of Infection in Developing CountriesPrevalence of hepatitis c among egyptian children with sickle cell disease and the role of IL28b gene polymorphisms in spontaneous viral clearance
2016, Mediterranean Journal of Hematology and Infectious Diseases