The following is a summary of “Differences in HDL-Bound Apolipoproteins in Patients With Advanced Liver Fibrosis Due to Nonalcoholic Fatty Liver Disease,” published in the January 2023 issue of Endocrinology & Metabolism by Bril, et al.

It was unclear what caused people with severe liver fibrosis and nonalcoholic fatty liver disease (NAFLD) to develop cardiovascular diseases more frequently. Therefore, patients with advanced fibrosis or NAFLD were evaluated for HDL-bound proteins.

There were 185 participants in the cross-sectional research at a university hospital, both with and without type 2 diabetes (T2D). To evaluate intrahepatic triglyceride buildup, patients received liver proton magnetic resonance spectroscopy, and those with NAFLD underwent a percutaneous liver biopsy. In addition, advanced lipid testing was carried out using measurements of the lipoprotein subfractions and targeted proteomics of HDL-bound proteins.

The clinical features of patients with and without extensive fibrosis were comparable, with the exception of decreased HDL-C (34 ± 8 vs. 38 ± 9 mg/dL, P = 0.024) and a greater incidence of T2D in advanced fibrosis. Advanced fibrosis patients exhibited a reduced number of HDL particles. Using tandem mass spectrometry and multiple reaction monitoring liquid chromatography, a panel of 28 HDL-bound proteins was identified and quantified. Patients with advanced fibrosis were shown to have lower levels of five proteins (ApoC-I [P < 0.001], ApoC-IV [P = 0.012], ApoM [P = 0.008], LCAT [P = 0.014], and SAA4 [P = 0.016]). Patients with or without NAFLD or steatohepatitis showed no changes in these proteins. Patients with advanced fibrosis had a substantially higher pCAD index, which was linked to coronary artery disease and cardiovascular death (97 ± 5 vs. 86 ± 25, P= 0.04).

Significant variations in HDL-bound protein levels were seen in patients with advanced fibrosis-related NAFLD, which translated into a higher pCAD index-based cardiovascular risk. The connection between liver disease & higher cardiovascular mortality in these individuals may be explained by different lipoprotein composition & function.

Reference: academic.oup.com/jcem/article-abstract/108/1/42/6731241