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- Title
Proteomic Analysis of Hepatic Fibrosis in HIV-Associated NAFLD Demonstrates Upregulation of Immune Response and Tissue Repair Pathways.
- Authors
Fourman, Lindsay T; Stanley, Takara L; Ockene, Mollie W; McClure, Colin M; Toribio, Mabel; Corey, Kathleen E; Chung, Raymond T; Torriani, Martin; Kleiner, David E; Hadigan, Colleen M; Grinspoon, Steven K
- Abstract
<bold>Background: </bold>HIV-associated NAFLD is characterized by a high prevalence of hepatic fibrosis as a strong clinical predictor of all-cause and liver-specific mortality.<bold>Methods: </bold>We leveraged data from a recent clinical trial to define the circulating proteomic signature of hepatic fibrosis in HIV-associated NAFLD. 183 plasma proteins within two high-multiplex panels were quantified at baseline and 12-months using proximity extension assays (Olink Cardiovascular III, Immuno-Oncology).<bold>Results: </bold>Twenty proteins were upregulated at baseline among participants with fibrosis stages 2-3 versus 0-1 (P ≤ 0.01, FDR ≤ 0.10). Proteins most differentially expressed included MMP-2 (P = 0.0004), IGFBP-7 (P = 0.001), and COL1A1 (P = 0.001). Proteins were enriched within pathways such as response to tumor necrosis factor (FDR = 1.03e-16), aminopeptidase activity (FDR = 1.20e-5), and positive regulation of apoptotic process (FDR = 8.17e-6). Key proteins also were found to directly relate to visceral adiposity and glucose intolerance, and to inversely correlate with CD4+ T-cell count. Within the placebo-treated arm, 11 proteins differentially increased among individuals with hepatic fibrosis progression over 12-months (P < 0.05).<bold>Conclusions: </bold>Among individuals with HIV-associated NAFLD, hepatic fibrosis was associated with a distinct proteomic signature involving upregulation of tissue repair and immune response pathways. These findings enhance our understanding of potential mechanisms and biomarkers of hepatic fibrosis in HIV.
- Subjects
NON-alcoholic fatty liver disease; HEPATIC fibrosis; INSULIN-like growth factor-binding proteins; PROTEOMICS; BLOOD proteins
- Publication
Journal of Infectious Diseases, 2023, Vol 227, Issue 4, p565
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiac475