Metabolomic-/Lipidomic-based Analysis of Plasma to Diagnose Hepatocellular Ballooning in Patients with Nonalcoholic Fatty Liver Disease: A Multicenter Study.

AIM Liver biopsy is still required for the diagnosis of hepatocellular ballooning and inflammation, which are important histological feature of nonalcoholic steatohepatitis (NASH). We conducted this multicenter, cross-sectional study to identify novel blood markers for the diagnosis of hepatocellular ballooning. METHODS We enrolled 176 patients, and 132 patients proven by liver biopsy as having NAFLD were classified as non-ballooning (ballooning grade 0) (n = 83) or ballooning (ballooning grade 1 and 2) (n = 49) by a central pathology review. We performed 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 the 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 the 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 noninvasive metabolic-/lipidomic-based plasma tests might be useful to distinguish between cases of NAFLD with and without hepatocellular ballooning.