LAUSR

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver disease worldwide. Elevated sex hormone–binding globulin (SHBG) levels have been observed in the setting of HIV and may protect against some metabolic disorders. We aimed to investigate whether higher SHBG levels may protect against NAFLD in men with/without HIV. Methods NAFLD was assessed using noncontrast computed tomography in 530 men in the Multicenter AIDS Cohort Study (MACS) who drank <3 alcoholic drinks/d and were uninfected with chronic hepatitis C or B (340HIV+, 190HIV-). Morning serum samples were tested for SHBG, total testosterone (TT), and adiponectin. Multivariable logistic regression was used to assess associations between HIV, SHBG, TT, adiponectin, and NAFLD. Results Median SHBG was highest among HIV+/NAFLD- men and lowest among HIV-/NAFLD+ men. Adjusted for demographics, HIV, visceral adiposity, HOMA-IR, TT, and PNPLA3 genotype, higher SHBG was associated with lower odds of NAFLD (odds ratio [OR], 0.52 per doubling; 95% confidence interval [CI], 0.34–0.80). In separate multivariable models without SHBG, HIV (OR, 0.46; 95% CI, 0.26–0.79) and higher adiponectin (OR, 0.66 per doubling; 95% CI, 0.49–0.89) were associated with lower NAFLD odds, whereas TT was not significantly associated (OR, 0.74 per doubling; 95% CI, 0.53–1.04). Adjusting for SHBG attenuated the associations of HIV (OR, 0.61; 95% CI, 0.34–1.08) and adiponectin (OR, 0.74; 95% CI, 0.54–1.02) with NAFLD. Conclusions SHBG levels were higher among HIV+ men, were independently associated with lower NAFLD, and could partially explain the associations of HIV and higher adiponectin with lower NAFLD in our cohort. These findings suggest that SHBG may protect against NAFLD, supporting further prospective and mechanistic studies.