<i>IL-10</i> Polymorphisms and Haplotypes Predict Susceptibility to Hepatocellular Carcinoma Occurrence in Patients with Hepatitis C Virus Infection from Northeast India

Abstract

Chronic hepatitis C virus (HCV) infection leads to variable outcomes, ranging from prolonged slow hepatic damage leading to cirrhosis, and hepatocellular carcinoma (HCC). Polymorphism in cytokines IL-10 and IL-12 that impact the immune response to HCV infection may play a role in determining this outcome. This study was aimed to determine if polymorphisms in <i>IL-10</i> and <i>IL-12B</i> contribute to HCV susceptibility and the risk of developing HCC in patients from Northeast India. <i>IL-10</i> - 1082, -819, -592 polymorphisms and <i>IL-12B</i> -1188 polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism in a total of 266 HCV-infected patients and 100 age- and sex-matched controls. In the HCV-infected subjects, 110 patients had chronic hepatitis C (CHC), 96 with liver cirrhosis, and 60 with HCC. Serum levels of <i>IL-10</i> were also measured and correlated with disease severity. Haplotype analysis for <i>IL-10</i> polymorphisms was carried out. Statistical data were analyzed using SPSS ver. 22.0. The frequency of <i>IL-10</i> - 592 AA genotype/A allele was significantly higher in HCC patients than in CHC patients. The intermediate IL-10-producing ACC haplotype was significantly more frequent in HCC and cirrhotic patients than in CHC patients. No significant association was found for <i>IL-10</i> - 819, -592 and <i>IL-12B</i> -1188 polymorphisms with the susceptibility to HCV infection or occurrence of HCC in HCV-infected patients. <i>IL-10</i> - 592 CA polymorphism and <i>IL-10</i> ACC haplotype are significant biomarkers of HCC in HCV-infected patients from Northeast India. Higher serum levels of IL-10 were also linked to higher disease severity.