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. 2019 Jun 11;6(7):ofz281.
doi: 10.1093/ofid/ofz281. eCollection 2019 Jul.

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

Ani Kardashian  1 , Yifei Ma  2 , Michael T Yin  3 , Rebecca Scherzer  2 , Olivia Nolan  4 , Francesca Aweeka  2 , Phyllis C Tien  2   5 , Jennifer C Price  2
Affiliations

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

Ani Kardashian et al. Open Forum Infect Dis. .

Abstract

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.

Keywords: HIV/HCV coinfection; kyn/trp ratio; liver fibrosis.

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Figures

Figure 1.
Figure 1.
Median kyn/trp ratio by infection status. Normal range of kyn/trp ratio is <0.027 µmole/µmole [30]. Abbreviation: HCV, hepatitis C virus.
Figure 2.
Figure 2.
Correlation of kyn/trp ratio with fibrosis-4 score (FIB-4) levels by infection status. No significant association was observed between kyn/trp ratio and FIB-4 in uninfected persons. Abbreviation: HCV, hepatitis C virus.
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