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

In human immunodeficiency virus (HIV)-associated nonalcoholic fatty liver disease (NAFLD), hepatic fibrosis was associated with a distinct proteomic signature involving up-regulation of tissue repair and immune response pathways. Findings enhance our understanding of potential mechanisms and biomarkers of NAFLD-related hepatic fibrosis in HIV. 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 alpha 1(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.

Automated summary

In HIV-associated NAFLD, hepatic fibrosis is characterized by a distinct proteomic signature involving up-regulation of tissue repair and immune response pathways. Understanding these mechanisms and biomarkers is important for the management of NAFLD-related hepatic fibrosis in HIV patients.