Higher plasma kynurenine-tryptophan ratio predicts incident hepatic fibrosis in women with HIV

OBJECTIVE: Chronic immune activation and microbial translocation may contribute to hepatic fibrosis in people with HIV. We evaluated whether plasma kynurenine-to-tryptophan (KT) ratio and other biomarkers of microbial translocation predict incident fibrosis in women with HIV. DESIGN: Longitudinal cohort study of 709 women with HIV from the Women's Interagency HIV Study with baseline plasma biomarkers and serial vibration-controlled transient elastography. Participants with baseline fibrosis or viral hepatitis were excluded. Outcomes included incident fibrosis, steatotic liver disease (SLD)-associated fibrosis, non-SLD fibrosis, and advanced fibrosis. METHODS: Poisson regression with robust standard errors clustered by participant was used to estimate incidence rate ratios (IRRs) for liver outcomes by log-transformed KT ratio, adjusted for demographic, metabolic, and HIV-related covariates. Models included an offset for follow-up time. Analyses were repeated for sCD163, sCD14, and I-FABP. RESULTS: Over a mean follow-up of 42 months, 18.7% developed incident fibrosis, of whom 74% had SLD; 8.3% developed advanced fibrosis. In adjusted models, each log-unit increase in KT ratio was associated with incident fibrosis (IRR 1.46, 95% CI 1.21-1.76) and advanced fibrosis (IRR 1.59, 95% CI 1.27-1.99). KT ratio was associated with non-SLD fibrosis (IRR 1.59, 95% CI 1.31-1.94), but not SLD-associated fibrosis (IRR 1.16, 95% CI 0.94-1.42). Higher sCD163 was associated with all liver outcomes, whereas sCD14 and I-FABP were not. CONCLUSIONS: Higher KT ratio independently predicted incident hepatic fibrosis in women with HIV, particularly non-SLD fibrosis, suggesting a steatosis-independent pathway involving microbial translocation and macrophage activation.