Evaluating the Association Between Sphingolipid Metabolites and Post-hepatectomy Liver Failure

Hepatectomy is an essential treatment for various benign and malignant diseases of the liver. However, post-hepatectomy liver failure (PHLF) is still a life-threatening complication after hepatectomy. The pathophysiological mechanism of PHLF has not yet been fully elucidated, and there is still a lack of effective strategies for either prevention or therapy of PHLF. Sphingolipids include ceramides (CER), sphingomyelins (SM), glycosphingolipids (GSL), sphingosine (SPH), and sphingosine-1-phosphate (S1P) are multi-functional lipids that regulates cell proliferation, cell survival, cell death, inflammation, tissue fibrosis, cancer cell metastasis, and invasion. Liver is a main organ for metabolizing sphingolipids, dysregulation of specific sphingolipids is associated with several liver diseases, therefore sphingolipids have been proposed to be biomarkers of liver diseases, including hepatitis, liver cancer, fatty liver diseases, and liver fibrosis. Moreover, several studies have shown CER, SPH and S1P are critical in regulating pathophysiology of liver diseases, including liver regeneration, necrosis, and inflammation. Given that PHLF causes dramatic dysregulation in biochemical metabolism in liver, the investigators hypothesize that dysregulation of sphingolipid metabolism may also occur in PHLF, and the dysregulation of specific sphingolipids may serve as a biomarker or regulator during progression and recovery of PHLF. This project will examine the association between sphingolipid metabolism and PHLF. Levels of sphingolipid metabolites and their related enzymes in plasma and liver tissue of patients with hepatic resection will be measured by using liquid chromatograph/electrospray ionization/mass spectrometry (LC-ESI-MS/MS) and high-throughput real-time quantitative PCR. This project will facilitate us to identify specific sphingolipid metabolites as biomarker and regulator of PHLF.