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

Maria J Duarte; Phyllis C Tien; Ani Kardashian; Yifei Ma; Peter Hunt; Mark H Kuniholm; Adaora A Adimora; Margaret A Fischl; Audrey L French; Elizabeth Topper; Deborah Konkle-Parker; Howard Minkoff; Ighovwerha Ofotokun; Michael Plankey; Anjali Sharma; Jennifer C Price

doi:10.1093/ofid/ofae187

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

Open Forum Infect Dis. 2024 Mar 30;11(5):ofae187. doi: 10.1093/ofid/ofae187. eCollection 2024 May.

Authors

Maria J Duarte¹, Phyllis C Tien², Ani Kardashian³, Yifei Ma², Peter Hunt⁴, Mark H Kuniholm⁵, Adaora A Adimora⁶, Margaret A Fischl⁷, Audrey L French⁸, Elizabeth Topper⁹, Deborah Konkle-Parker¹⁰, Howard Minkoff¹¹, Ighovwerha Ofotokun¹², Michael Plankey¹³, Anjali Sharma¹⁴, Jennifer C Price¹

Affiliations

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

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.

Keywords: HIV-associated liver disease; MASLD; microbiome; steatohepatitis; steatotic liver disease.

Grants and funding

T32 DK060414/DK/NIDDK NIH HHS/United States