Post-hepatectomy Liver FailureNCT03598465
Evaluating the Association Between Sphingolipid Metabolites and Post-hepatectomy Liver Failure
An observational study of Post-hepatectomy Liver Failure, run by Nanfang Hospital, Southern Medical University at 3 sites in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Post-hepatectomy Liver Failure
- How many people
- 591 participants
- Where
- 3 sitesChina
- Study dates
- 5 Mar 2019to 1 Oct 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Chinese patients who receive hepatectomy for benign or malignant disease in the department of Hepatobiliary Surgery of Nanfang Hospital Southern Medical University.
Who may be able to join
- Patients accepts hepatectomy
- In case of liver cancer, patient should received radical resection of R0 standards.
Who cannot join
- 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.
Trial locations and contacts
3 sites in 1 country.
China3 sites
The first people's hospital of Foshan
Foshan, Guangdong, 528300
Nanfang Hospital, Southern Medical University
Guangzhou, Guangdong, 510515
The second people's hospital of Shenzhen
Shenzhen, Guangdong, 518035
About this study
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.
Read the detailed 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.
- Conditions
- Post-hepatectomy Liver Failure
- Keywords
- Post-hepatectomy liver failure, Sphingolipids metabolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| PHLF Group | The investigators will define PHLF as a postoperatively acquired deterioration in synthetic, excretory, and detoxifying functions of liver. According to the PHLF definition and grading criteria established by International Liver Group of Liver Surgery (ISGLS) in 2011 (Surgery,2011,149(5):713-724), PHLF will be diagnosed by an increased PT-INR and concomitant hyperbilirubinemia on or after postoperative day 5. | |
| Non-PHLF Group | Non-PHLF will be defined as normal liver function in terms of normal PT-INR and bilirubin levels after hepatectomy on or after postoperative day 5. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Post-hepatectomy liver failure (PHLF)
Liver failure caused by hepatectomy. (Surgery,2011,149(5):713-724).
Measured: On or after postoperative day 5 of hepatectomy.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2018
- Study start5 Mar 2019
- Primary completion1 Sep 2024
- Study completion1 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Post-hepatectomy Liver FailureStudies of the same condition, open and under way.
- More trials run by Nanfang Hospital, Southern Medical UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 591 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nanfang Hospital, Southern Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jie Zhou, MD., Study director, Nanfang Hospital, Southern Medical UniversityKai Wang, MD.PhD., Principal investigator, Nanfang Hospital, Southern Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03598465
- Sponsor's protocol ID
- NFEC-2018-033
- Status last verified
- Nov 2024
- First submitted
- 16 Jul 2018
- Last updated
- 14 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Rahbari NN, Garden OJ, Padbury R, Brooke-Smith M, Crawford M, Adam R, Koch M, Makuuchi M, Dematteo RP, Christophi C, Banting S, Usatoff V, Nagino M, Maddern G, Hugh TJ, Vauthey JN, Greig P, Rees M, Yokoyama Y, Fan ST, Nimura Y, Figueras J, Capussotti L, Buchler MW, Weitz J. Posthepatectomy liver failure: a definition and grading by the International Study Group of Liver Surgery (ISGLS). Surgery. 2011 May;149(5):713-24. doi: 10.1016/j.surg.2010.10.001. Epub 2011 Jan 14.
PubMed 21236455Liang H, Liu H, Li J, Wang B, Huang P, Guo W, Zhuang B, Liao L, Li Q, Wu X, Peng T, Lai Z, Tang S, Zhu B, Gao J, Lin S, Huang C, Liu C, Zeng M, Qian J, Zhang Q, Zhou J, Deng X, Li C, Wang K. Prospective multicenter validation of preoperative plasma ceramides as novel predictive biomarkers for clinically relevant post-hepatectomy liver failure. Int J Surg. 2025 Oct 1;111(10):6843-6856. doi: 10.1097/JS9.0000000000002791. Epub 2025 Jun 24.
PubMed 40557443
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating the Association Between Sphingolipid Metabolites and Post-hepatectomy Liver Failure
- ClinicalTrials.gov ID
- NCT03598465
- Acronym / sponsor ID
- NFEC-2018-033
- Conditions
- Post-hepatectomy Liver Failure
- Keywords
- Post-hepatectomy liver failure, Sphingolipids metabolism
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 591 participants (actual)
- Lead sponsor
- Nanfang Hospital, Southern Medical UniversityUniversity, hospital or other
- Study start
- 5 Mar 2019 (actual)
- Primary completion
- 1 Sep 2024 (actual)
- Study completion
- 1 Oct 2024 (actual)
- First posted
- 26 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PHLF Group | – | –The investigators will define PHLF as a postoperatively acquired deterioration in synthetic, excretory, and detoxifying functions of liver. According to the PHLF definition and grading criteria established by International Liver Group of Liver Surgery (ISGLS) in 2011 (Surgery,2011,149(5):713-724), PHLF will be diagnosed by an increased PT-INR and concomitant hyperbilirubinemia on or after postoperative day 5. |
| Non-PHLF Group | – | –Non-PHLF will be defined as normal liver function in terms of normal PT-INR and bilirubin levels after hepatectomy on or after postoperative day 5. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Chinese patients who receive hepatectomy for benign or malignant disease in the department of Hepatobiliary Surgery of Nanfang Hospital Southern Medical University.
Key inclusion criteria (2 listed)
- Patients accepts hepatectomy
- In case of liver cancer, patient should received radical resection of R0 standards.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Post-hepatectomy liver failure (PHLF)
Time frame: On or after postoperative day 5 of hepatectomy.
Liver failure caused by hepatectomy. (Surgery,2011,149(5):713-724).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2024.
- Results publication: PubMed 21236455Rahbari NN, Garden OJ, Padbury R, Brooke-Smith M, Crawford M, Adam R, Koch M, Makuuchi M, Dematteo RP, Christophi C, Banting S, Usatoff V, Nagino M, Maddern G, Hugh TJ, Vauthey JN, Greig P, Rees M, Yokoyama Y, Fan ST, Nimura Y, Figueras J, Capussotti L, Buchler MW, Weitz J. Posthepatectomy liver failure: a definition and grading by the International Study Group of Liver Surgery (ISGLS). Surgery. 2011 May;149(5):713-24. doi: 10.1016/j.surg.2010.10.001. Epub 2011 Jan 14.
- Derived from this study: PubMed 40557443Liang H, Liu H, Li J, Wang B, Huang P, Guo W, Zhuang B, Liao L, Li Q, Wu X, Peng T, Lai Z, Tang S, Zhu B, Gao J, Lin S, Huang C, Liu C, Zeng M, Qian J, Zhang Q, Zhou J, Deng X, Li C, Wang K. Prospective multicenter validation of preoperative plasma ceramides as novel predictive biomarkers for clinically relevant post-hepatectomy liver failure. Int J Surg. 2025 Oct 1;111(10):6843-6856. doi: 10.1097/JS9.0000000000002791. Epub 2025 Jun 24.
- The definition and diagnostic criteria of post-hepatectomy liver failure were proposed by International Liver Group of Liver Surgery(ISGLS) in 2011.Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jie Zhou, MD. study director
Nanfang Hospital, Southern Medical University
Kai Wang, MD.PhD. principal investigator
Nanfang Hospital, Southern Medical University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Post-hepatectomy Liver Failure, run by Nanfang Hospital, Southern Medical University at 3 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Post-hepatectomy liver failure (PHLF) (time frame: On or after postoperative day 5 of hepatectomy.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03598465, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2024.