The proteomic signature of hepatic fibrosis in HIV-associated NAFLD


A team from Massachusetts General Hospital used the Olink® Target 96 CVD III and Immuno-oncology panels to identify circulating proteins associated with hepatic fibrosis in patients with HIV-associated non-alcoholic fatty liver disease (NAFLD). Around 30% of people living with HIV (PLWH) develop NAFLD and in these patients, the presence and progression of hepatic fibrosis is strongly associated with poor prognosis and mortality. Protein biomarkers related to fibrosis in these patients are lacking, so this study leveraged data from a clinical trial to define the proteomic signature of fibrosis presence and progression in NAFLD among a cohort of PLWH.


When comparing baseline levels between patients with fibrosis stages 2/3 versus 0/1, 20 proteins were upregulated, with the strongest associations seen for MMP-2, IGFBP-7 and COL1A1. Pathway analysis of the 20 proteins indicated response to tumor necrosis factor, aminopeptidase activity and positive regulation of apoptotic process as key biological functions. When individual proteins were examined in relation to specific clinical parameters, associations with visceral adiposity (including GFBP-7, GAl-4 and OPN), glucose intolerance (IGFBP-7 & TNFRSF9) and (inverse) correlation with CD4+ T-cell count (IGFBP-7) were found.

As an exploratory investigation, they also looked at differences in protein levels between samples taken at baseline and 12 months, comparing patients with or without fibrosis progression (taken from the placebo-treated patients in the trial). Here they saw that 11 proteins increased over 12-months among individuals with versus without hepatic fibrosis progression. As with the baseline analysis, tissue repair and immune response pathways were the most associated biological pathways linked to the proteins identified. Most notably, TNFRSF9 and Gal-4, which were upregulated among individuals with significant hepatic fibrosis at baseline, were also found to increase in association with hepatic fibrosis progression in this independent analysis.



Fourman LT, Stanley TL, Ockene MW, et al. Proteomic Analysis of Hepatic Fibrosis in HIV-Associated NAFLD Demonstrates Upregulation of Immune Response and Tissue Repair Pathways. (2022) Journal of Infectious Diseases, DOI: 10.1093/infdis/jiac475

This study uncovers potential mechanisms and biomarkers of hepatic fibrosis in HIV-associated NAFLD, which have implications for disease detection and drug discovery

Fourman et al. (2022)

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