title: Serum sphingolipids reflect the severity of chronic HBV infection and predict the mortality of HBV-acute-on-chronic liver failure.
abstract: Patients with HBV-acute-on-chronic liver failure (HBV-ACLF) have high mortality and frequently require liver transplantation; few reliable prognostic markers are available. As a class of functional lipids, sphingolipids are extensively involved in the process of HBV infection. However, their role in chronic HBV infection remains unknown. The aim of this study was to determine the serum sphingolipid profile in a population of patients with chronic HBV infection, paying special attention to exploring novel prognostic markers in HBV-ACLF. High performance liquid chromatography tandem mass spectrometry was used to examine the levels of 41 sphingolipids in 156 serum samples prospectively collected from two independent cohorts. The training and validation cohorts comprised 20 and 28 healthy controls (CTRL), 29 and 23 patients with chronic hepatitis B (CHB), and 30 and 26 patients with HBV-ACLF, respectively. Biometric analysis was used to evaluate the association between sphingolipid levels and disease stages. Multivariate analysis revealed difference of sphingolipid profiles between CHB and HBV-ACLF was more drastic than that between CTRL and CHB, which indicated that serum sphingolipid levels were more likely to associate with the progression HBV-ACLF rather than CHB. Furthermore, a 3-month mortality evaluation of HBV-ACLF patients showed that dhCer(d18 : 0/24 : 0) was significantly higher in survivors than in non-survivors (including deceased patients and those undergoing liver transplantation, p < 0.05), and showed a prognostic performance similar to that of the MELD score. The serum sphingolipid composition varies between CTRL and chronic HBV infection patients. In addition, dhCer(d18 : 0/24 : 0) may be a useful prognostic indicator for the early prediction of HBV-ACLF.
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Qu
authors.affiliation: Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China.
authors.forename: Su-Jun
authors.initials: SJ
authors.lastname: Zheng
authors.affiliation: Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Cai-Sheng
authors.initials: CS
authors.lastname: Wu
authors.affiliation: Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China.
authors.forename: Zhong-Ping
authors.initials: ZP
authors.lastname: Duan
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Jin-Lan
authors.initials: JL
authors.lastname: Zhang
mesh_terms: D065290:Acute-On-Chronic Liver Failure / Q000097:blood* / Q000401:mortality / Q000821:virology; D000328:Adult; D015415:Biomarkers / Q000097:blood; D005260:Female; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000401:mortality / Q000473:pathology; D006801:Humans; D008297:Male; D011379:Prognosis; D012720:Severity of Illness Index; D013107:Sphingolipids / Q000097:blood*; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; D013107:Sphingolipids