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.