Single nucleotide polymorphisms in PNPLA3, ADAR-1 and IFIH1 are associated with advanced liver fibrosis in patients co-infected with HIV-1//hepatitis C virus

Abstract

Objective:Nonalcoholic fatty liver disease (NAFLD), insulin resistance and liver fibrosis are prevalent in individuals co-infected with HIV type 1 (HIV-1)/hepatitis C virus (HCV), even after HCV eradication. Our aim was to evaluate single nucleotide polymorphisms (SNPs) associated with advanced liver fibrosis in HIV-1/HCV co-infected patients.Design/methods:In a cohort of 102 participants, we genotyped 16 SNPs in 10 genes previously associated with NAFLD and the innate immune response and correlated the genotypes with liver fibrosis and fat accumulation.Results:Multinomial logistic regression analysis identified three metabolic parameters that were significantly associated with advanced liver fibrosis (stage F3-F4): Albumin [odds ratio (OR) 0.80, 95% confidence interval (CI) 0.69-0.91, P=0.001], percentage of visceral fat area (PVFA) (OR 1.06, 95% CI 1.01-1.12, P=0.03) and BMI (OR 1.47, 95% CI 1.22-1.77, P<0.0001). After adjustment for sex, albumin, PVFA and BMI, we found that three SNPs were significantly associated with advanced fibrosis, one each in PNPLA3/rs738409 (P=0.016), ADAR-1/rs1127313 (P=0.029) and IFIH1/rs1990760 (P=0.033).Conclusion:Our results indicate that genotyping for these SNPs can be a useful predictive tool for liver fibrosis progression and liver fat accumulation in patients co-infected with HIV-1/HCV.