Role of serum level and genetic variation of IL-28B in interferon responsiveness and advanced liver disease in chronic hepatitis C patients

Abstract

Interleukin-28B (IL-28B) is suspected to be associated with response to treatment and one of the basic immunological backgrounds in liver transplant candidate (LTC). We aimed to assess whether genotypes of IL-28B can play a role in therapeutic response or advanced stages of liver disease. A total of 364 subjects were genotyped for IL-28B rs12979860 and rs8099917 SNPs using PCR-RFLP assay. Moreover, IL-28 serum level, HCV loads, and genotype were performed. A significant increase was observed in the frequencies of unfavorable rs12979860 genotypes/CT + TT in the chronic hepatitis C (CHC) and LTC groups. In the case of rs8099917, CHC group had a significantly higher frequency of unfavorable genotypes/GT + GG compared to the healthy group. IL-28B serum level was also significantly higher in healthy group compared with the CHC and LTC groups. There were no differences in the distribution of the IL-28B genotypes and haplotypes between responder and non-responder patients. Our results suggest, for the first time, that unfavorable rs12979860 genotypes can be considered one of the important immunological backgrounds in the Iranian LTC population that was confirmed with the lower IL-28 serum level compared to healthy group. Besides, there was a possible association of favorable IL-28B genotypes with lower odds of susceptibility to CHC infection but no support for a positive association between analyzed SNPs and an outcome of therapy. Moreover, non-CT haplotypes may be regarded as a genetic risk factor that can increase the chance of infection with HCV and progression toward end-stage HCV-related liver disease.

Elevated serum levels of adiponectin and interlukin-28B after IFN/RIB therapy in hepatitis C virus-infected patients

“…This was also reported regarding IL28 serum levels between patients with SVR and non-SVRs. These results are consistent with the results obtained by Alborzi et al [43] but inconsistent with the investigation performed by Fateh et al [44]. In accordance with Shi et al [45], in the present study, rs12979860 CT and rs8099917 TT genotypes of patients showed higher serum IL28 levels compared to CT and TT genotypes of healthy controls, respectively.…”

IFNΛ3/4 locus polymorphisms and IFNΛ3 circulating levels are associated with COPD severity and outcomes

“…Arpaci et al [40] found no association between genotype and circulating IFNL3 in patients with Hashimoto's Thyroiditis. Langhans et al [41] found that hepatitis C patients with the protective SNP rs12979860 CC genotype had more circulating IFNL3 compared to patients with the SNP rs12979860 TT genotype whereas Alborzi A., et al [42] found no association between circulating IFNL3 and genotype.…”

A Decline in Anti-Core+1 Antibody Titer Occurs in Successful Treatment of Patients Infected with Hepatitis C Virus

“…Hepatitis C virus (HCV) is an enveloped RNA virus with a 9.6-kb genome classified in the genus Hepacivirus of the family Flaviviridae (1)(2)(3). HCV is one of the leading causes of persistent infection in humans that can predispose to liver fibrosis and cirrhosis.…”

“…There are some reports indicating that chronic hepatitis C (CHC) infection is strongly associated with hepatocellular carcinoma (HCC) (3)(4)(5)(6)(7)(8)(9). There is neither effective vaccine for immunization, nor a broadly effective treatment for HCV infection (3).Among different factors associated with chronic HCV infection, alternate reading frame protein (ARFP) or core+1 protein is one the newest ones that can promote persistent infection (10)(11)(12). This protein is produced by a frame shift at codon 11 by a minority of ribosomes that initiate translation at the HCV AUG initiator codon of HCV genome (13,14).…”