ApoL1 and ApoJ as Novel Determinants of MASH: A cross-sectional study

Abstract Background Plasma apolipoproteins are linked to cardiometabolic dysfunctions, but their potential as biomarkers for metabolic dysfunction-associated steatohepatitis (MASH) remains underexplored. Methods Plasma levels of 14 apolipoproteins (apoA-I, A-II, A-IV, B100, C-I, C-II, C-III, D, E, F, H, J, L1, M) were measured using liquid chromatography-tandem mass spectrometry in a cross-sectional study of 148 individuals with obesity undergoing bariatric surgery. Participants were categorized based on liver histology into non-MASH (no liver alterations or simple steatosis, defined as ≥ 5% intrahepatic fat) and MASH (steatosis with ballooning and lobular inflammation, with or without fibrosis). Correlations with clinical and biochemical parameters were assessed via Spearman’s rank correlation, and associations with MASH were evaluated using logistic regression. Results Plasma levels of apoC-III and apoL1 were significantly higher in MASH participants compared to non-MASH participants, while the levels of other apolipoproteins did not differ significantly between the two groups. Higher plasma levels of apoE, apoL1 and apoJ were associated with increased odds of MASH, independently of age and sex. The associations for apoL1 and apoJ remained significant after adjusting for MASH risk factors, including insulin resistance, plasma triglycerides, waist circumference, and the AST/ALT ratio, as well as comorbidities such as diabetes, dyslipidemia, and hypertension. Conclusions Plasma apoJ and apoL1 may serve as potential biomarkers for diagnosing MASH in individuals with obesity, independent of traditional risk factors and comorbidities. Further validation in larger cohorts and exploration of the underlying biological mechanisms linking these apolipoproteins to MASH are warranted.