Plasma Lipid Profies Analyses Of Patients With Hepatitis B Virus-related Acute-on-chronic Liver Failure

Objectives:Detection of plasma lipidomic in patients with hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF),hepatitis B virus related-non acute-on-chronic liver failure(HBV-non-ACLF)and healthy controls.In order to find out the potential biological markers that can predict the occurrence and development of HBV-ACLF,to reveal the changes of lipid during the development of HBV-ACLF.The aim of this study was to provide theoretical bases for the early prediction of liver failure,the pathogenesis of HBV-ACLF and targeted therapy in patients with chronic HBV.Methods:High performance liquid chromatography-mass spectrometry was used for lipidomic analyses.Fasting-state plasma samples from 74 HBV-ACLF patients,86 hepatitis B virus-non-related acute-on-chronic liver failure(HBV-non-ACLF)patients(30 HBV-immune tolerant(HBV-IT)and 56 chronic hepatitis B),and 20 healthy controls(HC).Univariate and multivariate analyses examined changes in lipid species among patient groups and its correlation with clinical indexes.At the same time,HBV-ACLF patients were followed up for 6 months to analyze the relationship between lipid biomarkers and clinical outcomes(6-month survival rate).Results:The HBV-ACLF and HBV-non-ACLF groups had distinctly different lipid profiles,while the HC and HBV-IT groups had similar lipid profiles.Additionally,the concentrations of five lipid species[lysophosphatidylcholine(LPC)22:6,cholesterol ester(CE)22:6,CE20:4,CE18:2 and CE18:1]decreased with the worsening liver function,suggesting that they could be used as potential biomarkers for the early prediction of ACLF.Meanwhile,univariate and multivariate analyses selected CE20:4,LPC 16:0,LPC 18:0,phosphatidylcholine(PC)40:6 and PC32:0 as putative diagnosis biomarkers of HBV-ACLF.In the HBV-ACLF group,LPC16:0 and LPC18:0 were significantly negative associated with model for end-stage liver disease(MELD)scores.Moreover,In contrast to the individual predictive ability of LPC 16:0,LPC18:0 and MELD score for 6-months mortality of HBV-ACLF patients,the MELD score combined with LPC16:0/LPC18:0 reinforce the predictive value of mortality(LPC 16:0:AUC=0.714;LPC18:0:AUC=0.705;MELDscore:AUC = 0.749;LPC16:0/LPC18:0+MELD score:AUC=0.841).Conclusions:Our study revealed that lipid metabolism disorders were significantly associated with the severity of liver inflammatory injury in patients with chronic HBV infection.Specific lipid species could be used as potentially biomarkers for early prediction,diagnosis and prognostic evaluation in HBV-ACLF,and can effectively monitor the risk and progress of HBV-ACLF.