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

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

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.

Study Overview

• Status: Completed
• Conditions: Liver Transplantation; Transplant Recipient
• Intervention / Treatment: Procedure: sequential perfusion with ipv Ross solution and UW solution; Procedure: sole perfusion with UW solution

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 141
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200080
      • Shanghai First People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: sequential perfusion; 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; 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).
Placebo Comparator: sole perfusion; sole perfusion of liver grafts with high-viscosity UW solution only	Procedure: sole perfusion with UW solution; Totally 6 L of cold UW solution were infused (aortic: portal =1:1)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shanghai Jiao Tong University School of Medicine
• Investigators: Study Director: Zhi-Hai Peng, Prof., Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Publications and helpful links

General Publications

• Moench C, Moench K, Lohse AW, Thies J, Otto G. Prevention of ischemic-type biliary lesions by arterial back-table pressure perfusion. Liver Transpl. 2003 Mar;9(3):285-9. doi: 10.1053/jlts.2003.50015.
• Pirenne J, Van Gelder F, Coosemans W, Aerts R, Gunson B, Koshiba T, Fourneau I, Mirza D, Van Steenbergen W, Fevery J, Nevens F, McMaster P. Type of donor aortic preservation solution and not cold ischemia time is a major determinant of biliary strictures after liver transplantation. Liver Transpl. 2001 Jun;7(6):540-5. doi: 10.1053/jlts.2001.24641.
• Sanchez-Urdazpal L, Gores GJ, Ward EM, Maus TP, Buckel EG, Steers JL, Wiesner RH, Krom RA. Diagnostic features and clinical outcome of ischemic-type biliary complications after liver transplantation. Hepatology. 1993 Apr;17(4):605-9. doi: 10.1002/hep.1840170413.

Study record dates

Study Major Dates

• Study Start: July 1, 2004
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: December 30, 2010
• First Submitted That Met QC Criteria: January 5, 2011
• First Posted (Estimate): January 6, 2011

Study Record Updates

• Last Update Posted (Estimate): January 6, 2011
• Last Update Submitted That Met QC Criteria: January 5, 2011
• Last Verified: December 1, 2010

More Information

Terms related to this study

• Keywords: orthotopic liver transplantation; preservation solution; peribiliary plexus; nonanastomotic biliary strictures; primary non-function
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Constriction, Pathologic; Hypoglycemic Agents; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Vasodilator Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Antirheumatic Agents; Purinergic Agents; Antimetabolites; Protective Agents; Antioxidants; Free Radical Scavengers; Gout Suppressants; Purinergic P1 Receptor Agonists; Purinergic Agonists; Insulin; Pharmaceutical Solutions; Adenosine; Allopurinol
• Other Study ID Numbers: SFPH04618

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No