Background:
Non-alcoholic fatty liver disease (NAFLD) may be more common among people with HIV (PWH), but unique risk factors for NAFLD in PWH (NAFLD-PWH) are poorly understood. We examined the prevalence of and risk factors for NAFLD and advanced fibrosis (AF) in a cohort of PWH without other known causes of liver disease, as well as histological features of NAFLD in persons with and without HIV.
Methods:
In an ongoing prospective study, PWH ≥18 years of age on suppressive antiretroviral therapy (ART) were screened for NAFLD (controlled attenuation parameter ≥263 dB/m) and AF (liver stiffness measurement ≥11 kPa) using vibration controlled transient elastography. For histology, 107 biopsies each from NAFLD-PWH (cases) and NAFLD in people without HIV (controls) were matched on age/sex/race/ethnicity/BMI/ALT. Biopsies were centrally read using the NASH CRN scoring system. Logistic regression evaluated associations with NAFLD and AF.
Results:
PWH (n=654) had mean age 53 years, 73% male sex at birth, 51% were non-Hispanic Black and 20% Hispanic. NAFLD and AF prevalence were 53% and 6%, respectively. Older age, male sex, greater BMI or waist circumference and higher ALT and triglyceride concentrations associated with greater NAFLD odds, and non-Hispanic Black race with lower odds. Greater BMI or waist circumference, higher AST and alkaline phosphatase concentrations and lower platelet counts associated with greater odds of AF, and non-Hispanic Black race with lower odds (all p<0.05). NAFLD-PWH had less steatosis (63% grade 1/2 vs. 47%, p=0.01), less inflammation (70% grade 1/2 vs. 60%, p=0.03) and less hepatocyte ballooning (none: 61% vs. 45%, many 15% vs 27%, p=0.03) and portal inflammation (8% >mild vs. 21%) than controls. As a result, NAS was lower in NAFLD-PWH (3.2 ± 1.6 vs 4.0 ± 1.6, p<0.001), with a trend towards less steatohepatitis (61% vs. 71%, p=0.09). Regression analyses observed less steatosis, portal inflammation and ballooning but more fibrosis in NAFLD-PWH (all p<0.05).
Conclusions:
In summary, in our cohort of PWH undergoing systematic screening, NAFLD prevalence was high, with traditional metabolic risk factors but not HIV-/ART-specific characteristics dominating risk for NAFLD and AF. Traditional histologic drivers of fibrosis were less pronounced in NAFLD-PWH and yet fibrosis stage was higher vs. matched controls without HIV, suggesting HIV-specific factors beyond hepatic necroinflammation may contribute to fibrosis in NAFLD-PWH.