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Lindsay T Fourman, Takara L Stanley, Mollie W Ockene, Colin M McClure, Mabel Toribio, Kathleen E Corey, Raymond T Chung, Martin Torriani, David E Kleiner, Colleen M Hadigan, Steven K Grinspoon, Proteomic Analysis of Hepatic Fibrosis in Human Immunodeficiency Virus–Associated Nonalcoholic Fatty Liver Disease Demonstrates Up-regulation of Immune Response and Tissue Repair Pathways, The Journal of Infectious Diseases, Volume 227, Issue 4, 15 February 2023, Pages 565–576, https://doi.org/10.1093/infdis/jiac475
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Abstract
Human immunodeficiency virus (HIV)–associated nonalcoholic fatty liver disease (NAFLD) is characterized by a high prevalence of hepatic fibrosis as a strong clinical predictor of all-cause and liver-specific mortality risk.
We leveraged data from an earlier clinical trial to define the circulating proteomic signature of hepatic fibrosis in HIV-associated NAFLD. A total of 183 plasma proteins within 2 high-multiplex panels were quantified at baseline and at 12 months (Olink Cardiovascular III; Immuno-Oncology).
Twenty proteins were up-regulated at baseline among participants with fibrosis stages 2–3 versus 0–1. Proteins most differentially expressed included matrix metalloproteinase 2 (P < .001), insulin-like growth factor–binding protein 7 (P = .001), and collagen α1(I) chain (P = .001). Proteins were enriched within pathways including response to tumor necrosis factor and aminopeptidase activity. Key proteins correlated directly with visceral adiposity and glucose intolerance and inversely with CD4+ T-cell count. Within the placebo-treated arm, 11 proteins differentially increased among individuals with hepatic fibrosis progression over a 12-month period (P < .05).
Among individuals with HIV-associated NAFLD, hepatic fibrosis was associated with a distinct proteomic signature involving up-regulation of tissue repair and immune response pathways. These findings enhance our understanding of potential mechanisms and biomarkers of hepatic fibrosis in HIV.
