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.

Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with Non-alcoholic Fatty Liver Disease and Chronic Hepatitis B

“…The increased DAG and ceramide could mediate insulin resistance, oxidative stress, apoptosis, and endoplasmic reticulum stress, which are associated with lipotoxic liver injury in NASH 19 – 22 . Interestingly, our study found decreased serum total lipids, neutral lipids (TAG, DAG, CE), and sphingolipids (Cer, SM) in the CHB without NAFLD group, indicating that chronic active HBV infection may be inversely associated with hyperlipidemia and insulin resistance and may play beneficial roles on lipid profiles 20 , 21 , 23 , 24 . Increasing epidemiological studies have shown that chronic HBV infection is inversely associated with the metabolic syndrome and its some components 6 – 8 , 25 , 26 .…”

Serum sphingomyelin has potential to reflect hepatic injury in chronic hepatitis B virus infection

“…15 It is interesting to find the different kinds of sphingolipids in our previous findings related to the different causes and disease status. Additionally, it is confirmed that pathogens need to exploit lipid rafts, which sphingolipids are rich in, to get into the host cells 7,10 and proficient virus replication is crucially supported by lipid biosynthesis.…”

“…The HPLC-MS/ MS methodology used in this study was described in our previous report. 15 Sphingolipidomic assays were performed at the Institute of Materia Medica, Peking Union Medical College (Beijing, China).…”

“…13,14 Recently we also found that serum dihydroceramide may be a useful prognostic indicator for the early prediction of HBV-related acute-on-chronic liver failure. 15 According to the previous finding, we speculated that the one or subclass of sphingolipids might play different roles in different etiologies and progressing stage of liver disease, and certain sphingolipids might be involved in the hepatic injury caused by chronic HBV infection.…”

Serum Biomarker Identification by Mass Spectrometry in Acute Aortic Dissection

“…In general, the pathological processes of AD are thought to include the initial inflammatory response, degradation and destruction of vascular wall components and their release into the peripheral blood, and activation of the coagulation mechanism [11]. Therefore, recent identification of early peripheral blood biomarkers for AD has focused on markers for vascular endothelial injury and repair and inflammatory reactions in the early stage of the disease [12, 13]. The currently reported peripheral blood biomarkers for AD are all protein macromolecules, such as smooth muscle myosin heavy chain (smMHC), creatine kinase-BB (CK-BB), D-dimer, matrix metalloproteinases (MMPs), and elastin [14-16].…”