IL-28B genotypes as predictors of long-term outcome in patients with hepatitis C-related severe liver injury

Abstract

Introduction: Patients with severe fibrosis or cirrhosis are at high risk for liver-related complications, even after successful antiviral treatment and/or regression of fibrosis. These are the first published results concerning the role of IL-28B genotypes as predictors of the durability of sustained virological response (SVR) and long-term outcome, in patients with baseline severe fibrosis and cirrhosis caused by hepatitis C (HCV) infection.
 Methodology: Genetic testing for three different single nucleotide polymorphisms (SNP) near the IL28B gene, rs12979860, rs12980275 and rs8099917, was performed in 42 patients with HCV-related advanced fibrosis and cirrhosis, who achieved SVR after successful interferon-based treatment. Baseline clinical and laboratory parameters were analysed, as well as IL28B genotype association with late virological relapse, fibrosis progression and clinical outcomes.
 Results: The most prevalent genotypes in all three tested SNP positions were: CCrs12979860 genotype in 69% of patients, GTrs8099917 in 78.6% and GGrs12980275 in 47.6% of patients. The presence of IL28B CCrs12979860 genotype was identified as a negative predictor of late virological relapse. Further analysis did not confirm the association of other IL28B genotypes with the progression of fibrosis and clinical outcomes.
 Conclusions: Varying long-term prognosis in patients with HCV-related severe fibrosis and cirrhosis is due to multiple interactions between host genetic factors, virus and environment. These are first published results demonstrating the significance of IL28B CCrs12979860 genotype as a negative predictor of late virological relapse. A further investigation concerning genetic factors is necessary to identify patients under risk for late relapse, complications and unfavorable outcomes, so that they can be reevaluated and offered new treatment options.

Pharmacogenomics landscape of COVID-19 therapy response in Serbian population and comparison with worldwide populations

“…Frequency of C allele is in range of 22-44% for African populations, 62-85% for European populations, 70-77% for Southwest Asia, 65-89% for South Asia, 95% for Southeast Asia, 93-100% for East Asia, almost 100% for Oceania, 37-65% for North America and 20-80% for South American populations (53). Genotype frequency for CC rs12979860 genotype for Serbian HCV patients was 69% (54) which was in concordance with other European populations. However, three more studies on HCV patients in Serbia reported CC rs12979860 genotype frequencies from 25-56% (55)(56)(57).…”

Micro-elimination of HCV as a possible therapeutic strategy: our experience and a review of literature

“…Most of the patients (57.31%) do not have a significant degree of fibrosis, severe fibrosis is found in 9.67% and cirrhosis in 14.1% of patients [6]. Available scarce published data for Serbia including two decades of clinical observations, show that the following factors are negative predictors of sustained virologic response and had most certainly negative effect on the overall success rates with the dual therapeutic protocol: (predominance of unfavourable genotypes especially genotype 1 and advanced fibrosis or cirrhosis) [6,8,[9][10][11]. These conclusions are in concordance with overwhelming published data from high-income countries, with advanced surveillance strategies and reliable epidemiological data for chronic hepatitis C infection [12][13][14].…”

The first insight into the genetic structure of the population of modern Serbia

“…Ligands for this protein are the Human Leucocyte Antigen C (HLA-C) molecules and this interaction is involved in the immune response and dealing with various pathogen infections, including the Hepatitis C Virus (HCV) [45]. Variants in both KIR and HLA-C genes, as well as interleukin 28B (IL28B), affect the course of the HCV infection and the response to therapy [46,47]. Genotyping of these genes is therefore highly recommended in the clinical circumstances involving decisions about the anti-HCV treatment [46].…”