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

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.

• sequential perfusion with ipv Ross solution and UW solution (Procedure): 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).
• sole perfusion with UW solution (Procedure): Totally 6 L of cold UW solution were infused (aortic: portal =1:1)

Primary outcomes

• Number of participants with primary non-function (PNF) for safety assessment of sequential perfusion [1 week]: 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.
• Number of participants with nonanastomotic biliary strictures with a patent hepatic artery [5 years]: nonanastomotic biliary strictures secondary to hepatic arterial thrombosis or stenosis will be excluded from calculation.

Secondary outcomes

• Number of participants with initial poor function (IPF) [1 week]: 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.

Sex: All, ages: 18 Years to 65 Years

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

• 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. PMID 12619026
• 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. PMID 11443584
• 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. PMID 8477965

• Zhi-Hai Peng, Prof., Study director, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine