Prediction of response to sofosbuvir-based therapy using serum interleukin-12 and single nucleotide polymorphism of the interleukin 28B gene as predictive factors in HCV positive genotype-4 patients

Abstract

Some hepatitis-C virus patients have resistance to direct-acting-antivirals (DAAs). Genetic polymorphisms have been associated with drug resistance. This study aimed to evaluate the role of interleukin (IL)-28B gene polymorphism and IL-12 levels as predictors for a response to sofosbuvir/ribavirin (SOF/RBV) with (triple-therapy) or without (dual-therapy) Peg-alpha-interferon. 92 hepatitis C virus (HCV)/RNA (+)-patients treated with dual (n = 72) or triple (n = 20) therapy. IL28B genetic polymorphism and IL-12 level assessments. 30.4% of the patients were IL28B C/C genotype, 56.5% C/T-genotype, and 13% T/T-genotype. Mean baseline IL-12 levels were 27.5 ± 3.0 pg/mL. Rapid viral response was achieved in 86/92 patients. All patients achieved end-of-treatment virologic response. The 12- and 24-week sustained virologic responses (SVR) were achieved in 76 patients (82.6%), that is, a relapse was found in 16 patients (17.4%). 8 and 12-weeks after antiviral therapy, IL-12 levels decreased significantly, and became comparable to those of the control-group. That drop in IL-12 levels was similar across the dual- and triple-therapy patients. Finally, logistic regression analysis showed that the increase in baseline aspartate aminotransferase (AST) and T/T genotyping had an independent effect on increasing the probability a SVR failing in both dual- and triple-therapy groups (P = .0007 and P = .02, respectively). Single-nucleotide polymorphism (SNP) in IL-28B and IL-12 levels play roles as predictors in DAAs resistance.

A Synopsis of Hepatitis C Virus Treatments and Future Perspectives

“…Several studies have found an association between the host genetic factor, spontaneous clearance of the virus, the treatment response and the risk of fibrosis and/or hepatocarcinoma. Most studied single nucleotide polymorphisms (SNPs) are from the IL28B gene; however, several other SNPs in different genes have been involved: interferon-λ3, interferon-λ4, IL-12, TNF, IL-10 and Toll-like receptors 3 and 9 [131][132][133][134][135][136][137][138][139][140][141][142][143][144][145][146]. Moreover, a relationship has been recently shown between increased mortality and epigenetic changes related to age in a group of intravenous drug users coinfected with HCV-HIV [147].…”

“…Patients with the SNP rs12979860 CC polymorphism are more likely to achieve an SVR at 12 weeks of treatment with sofosbuvir/daclastavir in genotype 4-infected Egyptian patients [136]. This gene has been studied both as a predictor of response and as a factor of resistance to treatment in patients treated with sofosbuvir, raising the possibility of performing genetic analysis for the SNP in IL-28B before initiating antiviral treatment [139,140].…”