| BACKGROUND AND AIMS:The focus of this study was to discover noninvasive and reliable biomarkers for the diagnosis,disease-monitoring and prognosis of hepatitis B-related acute-on-chronic liver failure, and to disclose the pathogenesis and progression of Hepatitis B-related acute-on-chronic liver failure. Recent accumulating evidence indicates the biological actions of Autotaxin- Lysophosphatidic acid(ATX-LPA) signaling axis in liver disease.However, the role of ATX-LPA signaling axis in liver failure has not been reported.The present study aims to examined the alterations of serum ATX in hepatitis B-related acute-on-chronic liver failure and discuss whether serum ATX could be useful as an early warning parameter of hepatitis B-related acute-on-chronic liver failure.METHODS:Ultra-performance liquid chromatography-mass spectrometry(UPLC/MS) was used to analyse serum metabolites of 28 patients with hepatitis B-related acute-on-chronic liver failure, 35 patients with Child-Pugh A cirrhosis, 30 patients with chronic hepatitis B and 35 healthy volunteers. Characteristic metabolites were screened,identified and dynamically tracked to investigate their value for diagnosis,disease-monitoring and prognosis for hepatitis B-related acute-on-chronic liver failure.Meanwhile, serum ATX antigen was measured in 50 patients with hepatitis B-related acute-on-chronic liver failure, 11 patients with hepatitis B-related pre-ACLF, 39 patients with hepatitis B-related Child-Pugh A cirrhosis, 26 patients with chronic hepatitis B and 38 healthy volunteers by ELISA.RESULTS:After comparing serum metabolic profile of hepatitis B-related acute-on-chronic liver failure and Child-Pugh A cirrhosis, 99 characteristic metabolites were selected, and38 of them were identified. Dynamic tracking model demonstrated that 17metabolites(Lyso PC(18:0), L-Threonine, DHAP(18:0), Lyso PC(17:0), m/z =210.05, Acetoacetic acid, PA(20:4(5Z,8Z,11 Z,14Z)e/2:0, Lyso PC(15:0),Lyso PC(16:0), m/z = 258.818, Lyso PC(14:0), Phenylalanyl Phenylalanine, m/z= 475.172, Bilirubin glucuronide, m/z = 797.3, m/z =599.29 and m/z = 775.318)were related to prognosis of hepatitis B-related acute-on-chronic liver failure, and there were also 11 metabolites(Lyso PC(14:0), Phenylalanyl Phenylalanine, m/z =775.318,m/z = 475.172, Bilirubin glucuronide, m/z = 797.3,m/z = 599.29,Lyso PC(22:5), m/z = 759.286, m/z = 515.313 and m/z = 809.287) which improved with treatment in the survival group. Meanwhile, serum ATX antigen level was significantly higher in pre-ACLF than in Child-Pugh A cirrhosis and CHB but lower than in acute-on-chronic liver failure group, furthermore, patients of pre-ACLF deteriorated to acute-on-chronic liver failure have significant higher serum ATX levels than in patients that didn’t progress to acute-on-chronic liver failure. Serum ATX antigen levels were significantly higher among male acute-on-chronic liver failure patients with preclinical inflammation, SBP or pneumonia than ACLF without SBP or pneumonia, and alterations of ATX occured in the early stage of inflammation.Serum ATX antigen levels were well correlated with serum biochemical parameters of liver function including ALB, ALT, AST, ALP, TBIL, TBA, INR and MELD score.CONCLUSIONS:These observations contributed to the investigation of the mechanisms of hepatitis B-related acute-on-chronic liver failure manifestation and progression on the metabolic level, and they provided information for the identification of biomarkers for the diagnosis, disease-monitoring and prognosis of hepatitis B-related A acute-on-chronic liver failure. Meanwhile, serum ATX level may be a useful early warning parameter for acute-on-chronic liver failure. |
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