Liver Inflammation Is Common and Linked to Metabolic Derangements in Persons With Treated Human Immunodeficiency Virus (HIV).

Background: We sought to characterize in people with human immunodeficiency virus (PWH) the potential etiologies of elevated alanine aminotransferase (ALT) levels, which are common and often unexplained.
Methods: Participants from the longitudinal observational AIDS Clinical Trials Group HAILO cohort without a history of hepatitis C virus (HCV) or hepatitis B virus (HBV) infection nor reported heavy alcohol use were included. Clinical and demographic characteristics, including medication use, the hepatic steatosis index (HSI), and metabolic syndrome (MetS) were compared between participants with and without ALT elevation.
Results: Six hundred sixty-two participants were included; 444 (67%) had ≥1 and 229 (35%) ≥2 consecutive ALT elevations during a median of 4.0 years of follow-up. HSI and Hispanic or other (non-White or Black) race/ethnicity were consistently associated with higher odds of abnormal ALT (odds ratio [OR] 1.1 for HSI as a continuous variable, OR 1.9-2.8 for Hispanic/other race/ethnicity for ≥1 or ≥2 ALT elevations); older age and current smoking were associated with lower odds of abnormal ALT. Associations with metabolic disease, as well as with incident HBV and HCV infection, were strengthened by restricting outcomes to persistent and higher degrees of ALT elevation.
Conclusions: ALT elevation was common in this cohort of PWH and associated with metabolic disease and hepatic steatosis markers. Nonalcoholic fatty liver disease is likely a common cause of liver inflammation in PWH receiving suppressive antiretrovirals, deserving targeted diagnosis and intervention.
Competing Interests: Potential Conflicts of Interest. K. W. C. has received research funding to the institution from Merck Sharp & Dohme (grant) and Amgen (research contract), and served as a paid consultant for Pardes Biosciences, and reports payments and honoraria for CME presentations by a not-for-profit organization from International Antiviral Society-USA, and participation as Chair of a Safety Monitoring Committee for an investigator-initiated study where the sponsor is UCSF. F. J. P. has received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from ViiV, Janssen, Gilead, and Merck. S. N. has received research funding to the institution from Gilead Sciences and AbbVie Pharmaceuticals, served as a paid consultant for Pardes Biosciences, Theratechnologies, and Silverback Therapeutics, and served on an Advisory Board for Vir Biotechnology, a Data Safety Monitoring Board (DSMB) for Personal Health Insights, Inc, and an Event Adjudication Committee for Bristol-Myers Squibb/PRA, and reports stocks and stock options from Vir Biotechnology. E. T. O. has received research funding to the institution from Gilead Sciences and ViiV Healthcare, served as a consultant for ViiV Healthcare, Merck, and Theratechnologies, and reports stock or stock options from GSK, and since the completion of the analysis has become an employee of ViiV Healthcare. M. S. has served on a DSMB for Gilead and AbbVie, and on Advisory Boards for Abbvie, Arbutus, Assembly Bio, Antios, Gilead, GSK, Precision Bio, and Virion, and reports other financial or non-financial interests as the Editor, Journal of Viral Hepatitis, Wiley. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
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