High Kynurenine:Tryptophan Ratio Is Associated With Liver Fibrosis in HIV-Monoinfected and HIV/Hepatitis C Virus-Coinfected Women

Background: Tryptophan catabolism, measured by the kynurenine:tryptophan (kyn/trp) ratio, is associated with gut microbiota alterations in people with HIV (PWH). We examined the association of the kyn/trp ratio with liver fibrosis in women with/without HIV infection.

Methods: The plasma kyn/trp ratio was measured in 137 HIV-monoinfected, HIV/hepatitis C virus (HCV)-coinfected, and uninfected women in the Women's Interagency HIV Study. Fibrosis was estimated using FIB-4 in all participants and vibration-controlled transient elastography liver stiffness measurement (LSM) in a subset (n = 83). We used multivariable linear regression to evaluate the associations of infection status and kyn/trp ratio with relative differences in fibrosis estimates.

Results: The median kyn/trp ratio (interquartile range) was 0.056 (0.045-0.066) in HIV/HCV-coinfected, 0.038 (0.032-0.046) in HIV-monoinfected, and 0.031 (0.025-0.034) in uninfected women (P < .001). After adjustment for sociodemographic, lifestyle, and metabolic factors, HIV monoinfection and HIV/HCV coinfection were associated with 37% (95% confidence interval [CI], 9% to 73%) and 164% (95% CI, 100% to 250%) greater FIB-4, respectively. When kyn/trp ratio was included, higher kyn/trp ratio was associated with greater FIB-4 (27% per kyn/trp doubling; 95% CI, 5% to 53%), and the associations of HIV monoinfection (29% per kyn/trp doubling; 95% CI, 2% to 63%) and HIV/HCV coinfection (123% per kyn/trp doubling; 95% CI, 63% to 203%) with greater FIB-4 were attenuated. Among those with LSM, higher kyn/trp ratio was associated with greater LSM (43% per kyn/trp doubling; 95% CI, 15% to 79%) in multivariable analysis.

Conclusions: The kyn/trp ratio is elevated in PWH and is associated with greater liver fibrosis. Tryptophan catabolism may modify the relationships between HIV, HCV, and fibrosis.