Impact of Host IL28B rs12979860, rs8099917 in Interferon Responsiveness and Advanced Liver Disease in Chronic Genotype 3 Hepatitis C Patients

Abstract

Background and AimsGenetic polymorphisms near interleukin 28B gene are associated with spontaneous and treatment induced clearance of hepatitis C virus (HCV). Our objective was to evaluate the impact of interleukin 28B single nucleotide polymorphism (rs12979860, rs8099917) variability in HCV genotype 3 infected populations.Methods400 hepatitis C seroreactive patients from different population groups in Eastern and North Eastern part of India were assessed for host and viral genotypic analysis. 83 HCV genotype 3 infected patients were administered pegylated interferon- ribavirin therapy. Viral genotyping was performed using nested reverse transcriptase-PCR followed by direct sequencing methods. Host interleukin 28B genotyping was performed using real-time PCR based single nucleotide polymorphism analysis.ResultsOut of 400 hepatitis C seroreactive individuals, 73.25% were found to be RNA positive. HCV genotype 3 (65.87%) was found to be the major circulating strain in this region followed by genotype 1 (32.08%). rs12979860 CC genotype was significantly associated with sustained virological response in HCV genotype 3 infected population. In patients achieving rapid virological response, favourable CC/TT allele at rs12979860, rs8099917 was found to be predominant at both the alleles at 77%, 73.2% respectively; whereas in case of patients with relapsed HCV infection CT, TG alleles were found to be predominant. Additionally, CC genotypes at rs12979860 were found to be associated with sustained virological response in patients with high viral load (OR = 6.75, 0.05<p). HCV unfavourable rs12979860 TT, rs8099917 GG alleles were present in 34%, 27.6% patients with relapsed HCV infection respectively. Also unfavourable CT, TG genotypes were found to be predominant in patients with advanced stages of liver disease.ConclusionCC, TT the two favourable markers at SNPs rs12979860 and rs8099917 are strongly associated with sustained virological response in genotype 3 infected populations. This information will aid clinicians to effectively design response based treatment regimen.

Polymorphism in interferon λ3/interleukin‐28B gene and risk to noncirrhotic chronic hepatitis C genotype 3 virus infection and its effect on the response to combined daclatasvir and sofosbuvir therapy

“…Consistent with earlier studies, our data have shown that polymorphisms exist in the IFNL3/IL‐28B gene in North‐Indian population. The frequency of T allele (28%) of IFNL3 (rs12979860) was found to be similar that reported in Southern‐Indian (24%) population, Caucasians (30%‐32%) population, Moroccan (32%), whereas the Oriental population carry much lower frequency (5%‐8%) of the T allele .…”

“…The frequency of T allele (28%) of IFNL3 (rs12979860) was found to be similar that reported in Southern‐Indian (24%) population, Caucasians (30%‐32%) population, Moroccan (32%), whereas the Oriental population carry much lower frequency (5%‐8%) of the T allele . Similarly, the G allele frequency (17%) of IFNL3 (rs8099917) was quite similar to that reported earlier in the Eastern‐Indian (15%) population, Caucasians (16%) population, whereas the same for IFNL3 (rs8099917) is relatively lower in Oriental (5%‐9%) population …”

IL28B and ITPA Single Nucleotide Polymorphisms in a Cohort of Patients with HCV and HCV/HIV, Southern Brazil

“…The efficacy of PEG-INFα/RBV treatment depends, in part, on the interaction of virus and host factors [13], and SNPs may be associated with the outcome and response to treatment, specially IL28B and ITPA genotypes have been reported to be significant markers in recent trials [14,15]. For IL28B SNPs, SVR rates were higher in CC patients (54% in monoinfected patients and 67% in coinfected patients), findings similar to those reported in other studies [16][17][18]. Despite that, no significance was found, probably as a consequence of the small number of patients in both groups.…”

Interferon λ3 gene (IL28B) is associated with spontaneous or treatment‐induced viral clearance in hepatitis C virus–infected multitransfused patients with thalassemia

“…The Indian population is ethnically heterogeneous; therefore genetic variability is expected in different groups of the population. In our study population, frequencies of the favorable CC and TT genotypes at rs12979860 and rs8099917 were 53.14 and 69.84%, respectively, which is much less than that found in the study conducted by Firdaus and coworkers in chronic HCV Genotype 3 patients in the same region. It was seen in our study that the percentage of CC allele at rs12979860 was much higher (73%) in healthy individuals without thalassemia whereas our control individuals with thalassemia were found to have a low proportion of the same allele (53%) than normal controls.…”

“…In our earlier study, we found 18.7% HCV‐seroreactive cases in the population in this region with thalassemia major . Earlier studies have shown correlation of IL28B SNPs with IFN therapy in HCV chronic patients infected with Genotype 1 in Western countries and Genotype 3 in India . However, none of the previous studies have typically focused on any particular HCV‐infected high‐risk population group.…”