Risk Factors for Fatty Liver in the Multicenter AIDS Cohort Study

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Abstract
AIDS Cohort Study (MACS). METHODS: In 719 MACS participants who consumed less than three alcoholic drinks daily, fatty liver was defined as a liver-to-spleen attenuation ratio <1 on noncontrast computed tomography (CT). We genotyped single nucleotide polymorphisms in the patatin-like phospholipase domain-containing 3 (PNPLA3) gene and in other genes previously associated with nonalcoholic fatty liver disease. Risk factors for fatty liver were determined using multivariable logistic regression. RESULTS: Among 254 HIV-uninfected men and 465 HIV-infected men, 56% were White with median age 53 years and median body mass index 25.8 kg/m2. The vast majority of HIV-infected men (92%) were on ART, and 87% of the HIV-infected men were treated with a nucleoside reverse transcriptase inhibitor for a median duration of 8.5 years. Overall, 15% of the cohort had fatty liver, which was more common in the HIV-uninfected compared with the HIV-infected men (19 vs. 13%,P=0.02). In multivariable analysis, HIV infection was associated with a lower prevalence of fatty liver (odds ratio (OR)=0.44,P=0.002), whereas a higher prevalence of fatty liver was seen in participants withPNPLA3(rs738409) non-CC genotype (OR=2.06,P=0.005), more abdominal visceral adipose tissue (OR=1.08 per 10 cm2,P<0.001), and homeostatic model assessment of insulin resistance (HOMA-IR) ≥4.9 (OR=2.50,P=0.001). Among HIV-infected men,PNPLA3(rs738409) non-CC genotype was associated with a higher prevalence of fatty liver (OR=3.30,P=0.001) and cumulative dideoxynucleoside exposure (OR=1.44 per 5 years,P=0.02). CONCLUSIONS: CT-defined fatty liver is common among men at risk for HIV infection and is associated with greater visceral adiposity, HOMA-IR, andPNPLA3(rs738409). Although treated HIV infection was associated with a lower prevalence of fatty liver, prolonged exposure to dideoxynucleoside analogs is associated with higher prevalence....

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