Metabolomics Study Of HBV-induced Acute-on-chronic Liver Failure、 Chronic Liver Failure And Pre-acute-on-chronic Liver Failure

Background&AimsThe study was aim to find potential biomarkers that discriminate ACLF from CLF,and to search biomarkers associated with the severity of liver failure via compare serum metabolite profiles of ACLF with CLF and ACLF with Pre-ACLF.MethodsSerum samples were collected from patients with ACLF(n=57). CLF(n=56) and Pre-ACLF(n=49) as well as healthy individuals(n=20) and assayed by ultra performance liquid chromatography mass spectrometry(UPLC-MS).The multivariate data was analyzed with Smica-P to build a model discriminating ACLF from CLF and find potential biomarkers relating the severity of liver failure.ResultsThe metabolomic profile showed significant difference between ACFL and CLF, a partial least squares discriminant analysis(PLS-DA) model was established with satisfactory explanatory and predictive ability (R2=0.972, Q2=0.917),components that played important role in the separation were picked according to the variable importance in the Projection(VIP) Parameter. Metabolites that decreased significantly in the serum of ACLF and CLF included phosphatidylcholines(PCs) and lysophosphatidylcholines(LPCs),whereas conjugated bile acids (GCDCA,GUDCA) and Non-conjugated bile acids(CDCA) increased significantly,theses metabolites considered as common biomarkers of liver failure. Linoleyl camitine showed significant increase in CLF compared with controls while no significant change was observed in ACLF, so it considered as special biomarkers of ACLF and CLF. Significant change was also performed between ACLF and Pre-ACLF, PCs、LPs increased significantly while CDCA decreased in Pre-ACLF compared with ACLF, we may consider PCs、LPs has positive correlation with the severity of liver failure,on the contrary, CDCA has a negative correlation with liver failure.ConclusionWe build a PLS-DA model with satisfactory explanatory and predictive ability to discriminate ACLF and CLF, and identified biomarkers related to the severity of liver failure by analysis the metabolite profile of ACLF and Pre-ACLF, metabolomic analysis partly reveals the mechanism of liver failure and provide new insight into the research of liver failure.