Impact of IL12B Gene rs 3212227 Polymorphism on Fibrosis, Liver Inflammation, and Response to Treatment in Genotype 4 Egyptian Hepatitis C Patients

Abstract

Introduction. Hepatitis C virus (HCV) infection affects almost 3% of the world's population with the highest prevalence in Egypt (15%). The standard therapy; pegylated interferon (PEG-IFN) and ribavirin, is effective in only 60% of Egyptian patients; moreover it is costly, prolonged, and has severe side effects, so prediction of response is essential to reduce burden of unfavorable treatment. Several viral and host factors have been proved to affect response to the treatment PEG-IFN and ribavirin; the strongest of them is polymorphisms near IL28B; nonetheless, nonresponse in patients with favorable IL28B is still unexplained, which implies the importance of studying other immunological factors that may correlate with response. Interleukin 12 (IL-12) is one of the most important proinflammatory cytokine presented with the initiation of immune response, determining Th1 and Th2 differentiation. A functional single nucleotide polymorphism (A/C) at the 3′ untranslated region (3′UTR) at position 1188 (NCBI SNP database no 3212227) was reported to be associated with responding more efficiently to antiviral combination therapy in HCV genotype 1 infected patients. The present study aims to evaluate association between this polymorphism with fibrosis stages, necroinflammation activity, response to the combined therapy, and gender in Egyptian HCV genotype 4. Material and Methods. A total of 133 Egyptian chronic HCV (CHCV) patients were treated with IFN/RBV and were followed up. IL12B 1188 A/C genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PRC-RFLP) analysis. Results. A nonsignificant trend for higher sustained virological response (SVR) was observed in patients homozygote for IL12B 1188 A/C SNP CC genotype (69% SVR versus 30.8% NR) only but not in AC and AA genotypes. No association was detected between IL12B 1188 A/C polymorphism and less severe fibrosis or less liver activity. By stratification of response according to gender genotype, a significant difference in response between males and females was seen among AA genotype carriers only due to high number of non responder females. Conclusion. IL12B CC genotype appears to have some influence on SVR achievement but not on severe fibrosis and severe necroinflamation activity. Females carrying A/A genotype of IL12B 1188 A/C SNP achieve less SVR than those carrying AC and CC genotypes.

Serum Cytokine of IL-10 and IL-12 in Chronic Liver Disease: The Immune and Inflammatory Response

“…IL-12 is one of the most important proinflammatory cytokines presented with the initiation of immune response, determining Th1 and Th2 differentiation [ 1 ]. Capone et al [ 13 ] compared the serum level of numerous cytokines, chemokines, and growth factors in HC and LC patients with respect to those in HCC patients tested in their study.…”

“…Hepatitis C virus (HCV) infection affects almost 3% of the world's population with the highest prevalence (15%) in Egypt [ 1 ]. HCV infection results in chronic hepatitis in more than 70% of infected patients, while 20–30% of patients recover spontaneously [ 2 ].…”

The Epithelial-to-Mesenchymal Transition as a Possible Therapeutic Target in Fibrotic Disorders

“…Thus, a combination therapy approach that targets TGF-β, its regulating pathways and the associated inflammatory state may represent an option for liver fibrosis treatment ( Ebrahimkhani et al, 2011 ; Bai et al, 2013 ; Feng et al, 2013 ; Geng et al, 2020 ). In addition, other cytokines can stimulate the fibrotic process in the liver ( Tsuda et al, 2013 ; Youssef et al, 2013 ). For instance, IL-1β exerts fibrogenic effects similar to TGF-β, by inducing EMT.…”

A New Twist to a Chronic HCV Infection: Occult Hepatitis C

“… Prevalence of OCI in patients with chronic lymphoproliferative disorders (LPD). OCI was detected in 20% of the LPD group versus 4% in controls, adapted from [ 103 ]. …”