Fernando Bril, Ryan W Pearce, Timothy S Collier, Michael J McPhaul
The Journal of Clinical Endocrinology & Metabolism, Volume 108, Issue 1, January 2023, Pages 42–51
https://doi.org/10.1210/clinem/dgac565
The mechanisms leading to increased cardiovascular disease in patients with nonalcoholic fatty liver disease (NAFLD) and advanced liver fibrosis remain incompletely understood.
This study assessed HDL-bound proteins in patients with NAFLD with or without advanced fibrosis.
This cross-sectional study at a university hospital included 185 patients with or without type 2 diabetes (T2D). Patients underwent liver proton magnetic resonance spectroscopy to measure intrahepatic triglyceride accumulation and those with NAFLD underwent a percutaneous liver biopsy. Advanced lipid testing with lipoprotein subfraction measurements and targeted proteomics of HDL-bound proteins was performed.
Patients with and without advanced fibrosis had similar clinical characteristics, except for lower HDL-C (34 ± 8 vs 38 ± 9 mg/dL, P = 0.024) and higher prevalence of T2D in advanced fibrosis. Patients with advanced fibrosis had lower HDL particle number. A panel of 28 HDL-bound proteins were targeted and quantified by multiple reaction monitoring liquid chromatography–tandem mass spectrometry. Five proteins were found to be decreased in patients with advanced fibrosis (ApoC-I [P < 0.001], ApoC-IV [P = 0.012], ApoM [P = 0.008], LCAT [P = 0.014], and SAA4 [P = 0.016]). No differences were observed in these proteins in patients with vs without NAFLD or steatohepatitis. The pCAD index, associated with coronary artery disease and cardiovascular mortality, was significantly higher in patients with advanced fibrosis (97 ± 5 vs 86 ± 25, P = 0.04).
Patients with NAFLD with advanced fibrosis showed significant differences in HDL-bound protein levels; this translated into increased cardiovascular risk based on pCAD index. Different lipoprotein composition and function may explain the link between liver disease and increased cardiovascular mortality in these patients.
We provide our journal authors with a variety of resources for increasing the discoverability and citation of their published work. Use these tools and tips to broaden the impact of your article.
Read our special collections of Endocrine Society journal articles, curated by topic, Altmetric Attention Scores, and Featured Article designations.