Microbial Translocation and Gut Damage Are Associated With an Elevated Fast Score in Women Living With and Without HIV

Author:

Duarte Maria J1ORCID,Tien Phyllis C2,Kardashian Ani3,Ma Yifei2,Hunt Peter4ORCID,Kuniholm Mark H5,Adimora Adaora A6,Fischl Margaret A7,French Audrey L8,Topper Elizabeth9,Konkle-Parker Deborah10,Minkoff Howard11,Ofotokun Ighovwerha12,Plankey Michael13ORCID,Sharma Anjali14,Price Jennifer C1

Affiliation:

1. Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Francisco , San Francisco, California , USA

2. Department of Veterans Affairs Medical Center and Department of Medicine, University of California San Francisco , San Francisco, California , USA

3. Division of Gastroenterology and Liver Diseases, University of Southern California , Los Angeles, California , USA

4. Division of Experimental Medicine, University of California San Francisco , San Francisco, California , USA

5. Department of Epidemiology and Biostatistics, University at Albany, State University of New York , Rensselaer, New York , USA

6. Department of Medicine, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina , USA

7. Department of Medicine, Miller School of Medicine, University of Miami , Miami, Florida , USA

8. Department of Medicine, CORE Center/Stroger Hospital of Cook County , Chicago, Illinois , USA

9. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health , Baltimore, Maryland , USA

10. School of Nursing, Medicine and Population Health, University of Mississippi Medical Center , Jackson, Mississippi , USA

11. Department of Obstetrics and Gynecology, Downstate Health Sciences University, State University of New York , Brooklyn, New York , USA

12. Department of Medicine, School of Medicine, Emory University , Atlanta, Georgia , USA

13. Department of Medicine, Georgetown University Medical Center , Washington, DC , USA

14. Department of Medicine, Albert Einstein College of Medicine , Bronx, New York , USA

Abstract

Abstract Background Steatohepatitis is common in persons living with HIV and may be associated with gut microbial translocation (MT). However, few studies have evaluated the gut-liver axis in persons living with HIV. In the Women's Interagency HIV Study, we examined the associations of HIV and circulating biomarkers linked to MT and gut damage using the FibroScan–aspartate aminotransferase (FAST) score, a noninvasive surrogate for steatohepatitis with advanced fibrosis. Methods Among 883 women with HIV and 354 without HIV, we used multivariable regression to examine the associations of HIV and serum biomarkers linked to MT and gut damage (kynurenine and tryptophan ratio, intestinal fatty acid–binding protein, soluble CD14, and soluble CD163) with a log-transformed FAST score after adjusting for key covariates. We used a path analysis and mediation models to determine the mediating effect of each biomarker on the association of HIV with FAST. Results HIV infection was associated with a 49% higher FAST score. MT biomarker levels were higher in women with HIV than women without HIV (P < .001 for each). MT biomarkers mediated 13% to 32% of the association of HIV and FAST score. Conclusions Biomarkers linked to MT and gut damage are associated with a higher FAST score and mediate the association of HIV with a higher FAST score. Our findings suggest that MT may be an important mechanism by which HIV increases the risk of steatohepatitis with advanced fibrosis.

Funder

National Institutes of Health

Publisher

Oxford University Press (OUP)

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