Serum sphingolipids reflect the severity of chronic HBV infection and predict the mortality of HBV-acute-on-chronic liver failure

PLoS One. 2014 Aug 19;9(8):e104988. doi: 10.1371/journal.pone.0104988. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-On-Chronic Liver Failure / blood*
  • Acute-On-Chronic Liver Failure / mortality
  • Acute-On-Chronic Liver Failure / virology
  • Adult
  • Biomarkers / blood
  • Female
  • Hepatitis B, Chronic / blood*
  • Hepatitis B, Chronic / mortality
  • Hepatitis B, Chronic / pathology
  • Humans
  • Male
  • Prognosis
  • Severity of Illness Index
  • Sphingolipids / blood*
  • Survival Analysis

Substances

  • Biomarkers
  • Sphingolipids

Grants and funding

The work was supported by Ministry of Science and Technology of People's Republic of China (2012ZX09301002-006), National Science and Technology Key Project on “Major Infectious Diseases such as HIV/AIDS, Viral Hepatitis Prevention and Treatment” (2012ZX10002004-006, 2012ZX10004904-003-001, 2013ZX10002002-006-001), Beijing Municipal Natural Science Foundation (7102085), Beijing Municipal Science & Technology Commission (No. Z131107002213019); and High Technical Personnel Training Item in Beijing Health System (2011-3-083). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.