Genetic variants associated with steatohepatitis and liver fibrosis in HIV-infected patients with NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is a common cause of liver damage in people living with HIV (PLWHIV). Several studies have investigated candidate genes for susceptibility to NAFLD and to steatohepatitis. , , and have been reported to be associated with elevated ALT levels and the histologic parameters of nonalcoholic steatohepatitis and severity of fibrosis. Our objective was to analyze the relationship between , , and and steatosis, steatohepatitis, and liver fibrosis in PLWHIV with NAFLD. A cohort of PLWHIV with persistently elevated aminotransferase levels and suspected NAFLD who underwent liver biopsy and determination of genetic variants was assessed at two large centers in Spain. All participants included in the current study were genotyped for rs738409 (), rs58542926 (), and rs641738 (). The study population comprised PLWHIV who were on stable antiretroviral therapy [7.7% women; median age, 49.3 years (44-53.4)]. The median CD4 count was 829 (650-980), 60% had metabolic syndrome, and 18.5% were diabetic. The median BMI was 28.9 (25.5-30.8). Patients with liver steatosis (any grade) vs. nonsteatosis tended to harbor the G allele variant [57.6% vs. 16.7% ( = 0.09)], but not or variants. However, those with steatohepatitis vs. nonsteatohepatitis significantly more frequently had the G allele variant [69.4% vs. 39.1% ( < 0.05)] and the A allele variant [75% vs. 42% ( < 0.05)]. In our cohort, the gene variant was not associated with steatosis or steatohepatitis. The G allele variant was associated with steatohepatitis [OR 4.9 (1.3-18); p 0.02] and liver fibrosis [OR 4.3 (1.1-17.4); p 0.04], and the A allele variant was associated with steatohepatitis [OR 6.6 (1.6-27.6); p 0.01]. The G allele variant and A allele variant were associated with steatohepatitis and liver fibrosis in PLWHIV with persistently elevated aminotransferases and NAFLD. We recommend routine genotyping for and in PLWHIV with NAFLD to identify those at higher risk of progression.