Study of Sequential Perfusion of Liver Grafts to Prevent Nonanastomotic Biliary Strictures After Liver Transplantation

Study Overview
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Brief Summary
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The study was designed to investigate whether, compared with conventional sole perfusion with high-viscosity solution of University of Wisconsin (UW), sequential perfusion of liver grafts with low-viscosity and high-viscosity preservation solutions could further decrease the incidence of nonanastomotic biliary strictures (NAS) after liver transplantation.

Detailed Description
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The exact etiology of nonanastomotic biliary strictures (NAS) with a patent hepatic artery after liver transplantation remains unclear so far. Microangiopathy is strongly suspected to be involved in the etiology, so sufficient flushing of peribiliary plexus (PBP) which directly nourishes the donor biliary tree may be pivotal to prevent NAS with a patent hepatic artery. Solution of University of Wisconsin (UW solution) is a standard for liver graft flushing, but accused of high viscosity and hyperaggregation effect on erythrocytes by ingredient hydroxyethyl starch as well as initial vasoconstriction by high potassium content, which together constitutes a hindrance to solution penetration and thorough flushing of liver microcirculation including PBP. Several studies have revealed the relationship of high viscosity of UW solution with the development of NAS. The investigators, therefore, have hypothesized that sequential perfusion with low-viscosity and high-viscosity preservation solutions might improve the patency of PBP in contrast with conventional sole perfusion with high-viscosity UW solution, and as a result, the incidence of NAS with a patent hepatic artery after liver transplantation would be significantly decreased.

Official Title
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Study of Sequential Perfusion of Liver Grafts With Low-viscosity and High-viscosity Preservation Solutions to Decrease the Incidence of Nonanastomotic Biliary Strictures After Liver Transplantation

Conditions
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Liver Transplantation, Transplant Recipient

Intervention / Treatment
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* Procedure: sequential perfusion with ipv Ross solution and UW solution
* Procedure: sole perfusion with UW solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age≥18 years ability to provide written informed consent prior to study entry receiving a whole liver graft primary transplantation Exclusion Criteria: participant in other clinical trials fulminant liver failure as the cause of transplantation primary biliary cirrhosis, autoimmune hepatitis or primary sclerosing cholangitis as primary liver disease retransplantation non-liver organ(s) failure prior to study entry donor/recipient ABO-blood-group-incompatibility

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: sequential perfusion<br>sequential perfusion of liver grafts with low-viscosity improved Ross solution and high-viscosity UW solution. | Procedure: sequential perfusion with ipv Ross solution and UW solution<br>* Totally 6 L of ipv Ross solution were initially infused (aortic: portal=1:1), followed by 2 L of cold UW solution infusion (aortic: portal=1:1).<br>|
| Placebo Comparator: sole perfusion<br>sole perfusion of liver grafts with high-viscosity UW solution only | Procedure: sole perfusion with UW solution<br>* Totally 6 L of cold UW solution were infused (aortic: portal =1:1)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with primary non-function (PNF) for safety assessment of sequential perfusion | PNF is defined as non-life-sustaining function of the graft unexplained by vascular complications or rejection, leading to death or retransplantation within postoperative 7 days. | 1 week | 
| Number of participants with nonanastomotic biliary strictures with a patent hepatic artery | nonanastomotic biliary strictures secondary to hepatic arterial thrombosis or stenosis will be excluded from calculation. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with initial poor function (IPF) | IPF is defined as a delayed function restoration with serum AST level greater than 2,000 U/L and prothrombin time greater than 16 seconds postoperative days 2 to 7. | 1 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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orthotopic liver transplantation, preservation solution, peribiliary plexus, nonanastomotic biliary strictures, primary non-function