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

  • STATUS
    Recruiting
  • days left to enroll
    52
  • participants needed
    202
  • sponsor
    Nanfang Hospital of Southern Medical University
Updated on 22 January 2021

Summary

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.

Description

Liver resection is an effective treatment for both benign and malignant liver diseases. However, post-hepatectomy liver failure (PHLF) is still a life-threatening complication of liver resection. The pathophysiological mechanism of PHLF has not yet been fully studied, and there is still a lack of effective strategies for either prevention or therapy of PHLF. The investigation on PHLF has important clinical significance.

Sphingolipids are a group of bioactive lipids, including ceramides (CER), sphingomyelins (SM), glycosphingolipids (GSL), etc. CER are the basic structure that constitute sphingolipids. CER are composed of long-chain bases of sphingosine and different fatty acid carbon chains. CER are of various species. According to the saturation of fatty acid carbon chains, CER can be divided into saturated CER and unsaturated CER. CER can be divided into four species, including short chain (less than 6 carbon atoms), medium chain (6-12 carbon atoms), long chain (14-20 carbon atoms), and super long chain (more than 22 carbon atoms) . Pathways of CER generation include de novo synthesis, complex sphingolipid lipid degradation pathways, and salvage synthesis pathways. CER are degraded to produce sphingosine (SPH), which can be phosphorylated to produce S1P. CER and its metabolites SPH and S1P are enigmatic lipids that regulates cell survival, death, inflammation, tissue fibrosis, cancer metastasis, and cancer invasion. Hepatocytes express activities of various sphingolipid enzymes, which makes liver an important organ for sphingolipid metabolism. Emerging evidences have shown that dysregulation of sphingolipid metabolite are associated with development and progression of certain liver diseases. In animal studies, dysregulation of ceramides has been indicated in hepatocyte survival, liver injury, and liver failure. In clinical studies, dysregulation of specific ceramide species has been identified to be associated with decompensation of cirrhosis, liver fibrosis, hepatitis, hepatocellular carcinoma. In the light of these evidences, the investigators hypothesize that dysregulation of sphingolipid metabolism may be associated with PHLF.

The investigators have established a quantitative method to measure different types of sphingolipids in human plasma, tissues, and cells using liquid chromatograph/electrospray ionization/mass spectrometry (LC-ESI-MS/MS), including C12-CER, C16-CER, C18-CER, C18:1-CER, C20-CER, C22-CER, C24-CER, C24:1-CER, SPH, S1P, C12-SM, C12-LacCER, C12-GluCER. In order to examine the correlation between sphingolipid metabolism and PHLF, the investigators will collect plasma of patients during peri-operation period of hepatectomy, after lipid extraction, the levels of sphingolipids will be measured by LC-ESI-MS/MS technology. Moreover, expression of sphingolipid-metabolizing enzymes in liver issues will be determined using high-throughput real-time quantitative PCR. The diagnostic criteria and grading of PHLF will be performed following criteria of International Liver Group of Liver Surgery. In the end, the investigators will analyze the correlation between sphingolipid metabolites and PHLF. This project will facilitate us to identify specific sphingolipid metabolites as biomarker and regulator of PHLF, and shed the light on the study of PHLF prevention and therapy.

Details
Condition Post Hepatectomy Liver Failure
Clinical Study IdentifierNCT03598465
SponsorNanfang Hospital of Southern Medical University
Last Modified on22 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Patients accepts hepatectomy
In case of liver cancer, patient should received radical resection of R0 standards

Exclusion Criteria

Liver cancer invaded portal vein, common hepatic duct, hepatic vein trunk and/or inferior vena cava. Or the presence of extrahepatic metastases
Biliary obstruction, or surgery with exploration and reconstruction of bile duct
Surgery with splenectomy or splenic artery ligation
Patients with significant heart, lung, kidney and other organs of major diseases before surgery
The patients died in 90 days after surgery except for PHLF
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note