ApoJ and apoL1 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 quantified using liquid chromatography-tandem mass spectrometry in a cross-sectional study of 148 individuals with obesity undergoing bariatric surgery. Based on liver histology, participants were categorized as non-MASH (n = 94; no liver alterations or simple steatosis, ? 5% intrahepatic fat) or MASH (n = 54; 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. Incremental predictive value beyond established risk factors was assessed through likelihood ratio tests (LRT), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: ApoC-III and apoL1 were significantly higher in MASH compared with non-MASH participants, while other apolipoproteins showed no group differences. Higher apoE, apoL1 and apoJ levels were associated with increased odds of MASH, independently of age and sex. Associations for apoL1 and apoJ remained significant after adjustment for diabetes, dyslipidemia, and hypertension, or for established MASH risk factors including insulin resistance, triglycerides, waist circumference, and the AST/ALT ratio. LRT analyses showed that apoJ (?Deviance = 4.085, p = 0.043) and apoL1 (?Deviance = 3.954, p = 0.047) each improved model fit, with their combination providing additional improvement (?Deviance = 7.534, p = 0.023). NRI analysis indicated that the combination of apoJ and apoL1 provided the largest improvement (NRI total = 0.39, p = 0.026), mainly by correctly reclassifying non-MASH individuals (NRI non-event = 0.31, p = 0.0023). IDI was also greatest for the combination (IDI = 0.04, p = 0.034), indicating enhanced discrimination between MASH and non-MASH individuals. In an external cohort, the elevation of plasma apoJ in MASH was consistently replicated, whereas apoL1, apoC-III, and apoE showed no such pattern. CONCLUSIONS: Plasma apoJ and apoL1 may serve as potential biomarkers for diagnosing MASH in individuals with obesity, independent of traditional risk factors. Further validation in larger cohorts and mechanistic studies is warranted.