Proteomic Analysis of Hepatic Fibrosis in Human Immunodeficiency Virus-Associated Nonalcoholic Fatty Liver Disease Demonstrates Up-regulation of Immune Response and Tissue Repair Pathways.

Autor:	Fourman LT; Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA., Stanley TL; Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA., Ockene MW; Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA., McClure CM; Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA., Toribio M; Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA., Corey KE; Liver Center, Gastroenterology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA., Chung RT; Liver Center, Gastroenterology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA., Torriani M; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA., Kleiner DE; Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA., Hadigan CM; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA., Grinspoon SK; Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2023 Feb 14; Vol. 227 (4), pp. 565-576.
DOI:	10.1093/infdis/jiac475
Abstrakt:	Background: 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. Methods: 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). Results: 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). Conclusions: 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. Competing Interests: Potential conflicts of interest . L. T. F. has served as a consultant for Theratechnologies. T. L. S. has served as a consultant for Theratechnologies and reports research funding from Novo Nordisk. K. E. C. reports research funding from Boehringer Ingelheim and has served as a consultant to Novo Nordisk and Bristol Myers Squibb. R. T. C. reports research funding from AbbVie, Gilead, Merck, Bristol Myers Squibb, Boehringer Ingelheim, Janssen, and Roche. S. K. G. has served as a consultant (personal) and currently serves as a consultant through an institutional consulting agreement with Theratechnologies; Massachusetts General Hospital has a royalty and license agreement with Theratechnologies for Tesamorelin. S. K. G. is the inventor on a patent entitled “GHRH or Analogues Thereof For Use in Treatment of Hepatic Disease” (application 16832128). 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. (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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