Metabolomic/lipidomic‐based analysis of plasma to diagnose hepatocellular ballooning in patients with non‐alcoholic fatty liver disease: A multicenter study

AIM: Liver biopsy is still required for the diagnosis of hepatocellular ballooning and inflammation, which are important histological features of non-alcoholic steatohepatitis. We undertook this multicenter, cross-sectional study to identify novel blood markers for the diagnosis of hepatocellular ballooning. METHODS: We enrolled 176 patients, of whom 132 were proven by liver biopsy as having non-alcoholic fatty liver disease (NAFLD) and classified as non-ballooning (ballooning grade 0) (n = 83) or ballooning (ballooning grade 1 and 2) (n = 49) by a central pathology review. We carried out gas chromatography-mass spectrometry, hydrophilic interaction liquid chromatography tandem mass spectrometry, and lipidomics with plasma. RESULTS: As correlates of hepatocellular ballooning, among the clinical parameters, serum type IV collagen 7S correlated most significantly with the ballooning grade (correlation coefficient [CC] = 0.463; P < 0.001). Among the metabolic/lipidomic markers, phosphatidylcholine (PC) (aa-44:8) correlated most significantly with the ballooning grade (CC = 0.394; P < 0.001). The area under the receiver operating characteristic curve of type IV collagen 7S, choline, and lysophosphatidylethanolamine (LPE) (e-18:2), was 0.846 (95% confidence interval, 0.772-0.919). CONCLUSIONS: Plasma levels of PC were positively correlated, and those of lysophosphatidylcholine and LPE were negatively correlated with hepatocellular ballooning in NAFLD patients. These non-invasive metabolic/lipidomic-based plasma tests might be useful to distinguish between cases of NAFLD with and without hepatocellular ballooning.