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, 2022
Fourman L., Stanley T., Ockene M., McClure C., Toribio M., Corey K., Chung R., Torriani M., Kleiner D., Hadigan C., Grinspoon S.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Hepatology | Pathophysiology Patient Stratification | Plasma |  Olink Target 96 |
Abstract
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.