Microbial translocation and gut damage is associated with hepatic fibrosis but not steatosis in women with and without HIV.

OBJECTIVE: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent in people living with HIV (PWH). Gut microbial translocation and gut damage may play a role in MASLD pathogenesis. We determined associations of circulating biomarkers of translocation and gut damage with hepatic steatosis and fibrosis in a large U.S. cohort of women with HIV (WWH) and without HIV.

DESIGN: Vibration controlled transient elastography (VCTE) was conducted from 2013 to 2018 among 854 WWH and 349 women without HIV. Serum biomarkers were measured within 6 months of the VCTE: kynurenine to tryptophan (KT) ratio, intestinal fatty acid binding protein (I-FABP), and immune activation markers soluble CD14 (sCD14) and soluble CD163 (sCD163).

METHODS: We used multivariable linear regression to evaluate independent associations of each biomarker, HIV serostatus, and demographic, metabolic, and HIV-specific covariates with hepatic steatosis [controlled attenuation parameter (CAP)] and fibrosis [liver stiffness (LS)].

RESULTS: In multivariable analysis, increasing in KT ratio was associated with a 6 dB/m lower CAP and 6% higher LS, and sCD14 with a 5 dB/m lower CAP and 8% higher LS. sCD163 was not associated with CAP but was associated with a 12.5% higher LS value. I-FABP was not associated with either CAP or LS values.

CONCLUSIONS: Higher KT ratio, sCD14, and sCD163 were associated with increased hepatic fibrosis but not steatosis. In fact, higher KT ratio and sCD14 were associated with decreased steatosis. This suggests that microbial translocation and gut damage may contribute to the pathogenesis of fibrosis in WWH in a mechanism unrelated to increased steatosis.