Effect of Intermittent Hepatic Inflow Occlusion During Donor Hepatectomy In Living Donor Liver Transplantation

Effect of Intermittent Hepatic Inflow Occlusion During Donor Hepatectomy In Adult Living Donor Liver Transplantation Using Right Hemiliver Grafts

Intermittent hepatic inflow occlusion (IHIO), also called Pringle maneuver, is a safe and effective procedure for major hepatectomy in patients with liver disease. In addition, ischemic preconditioning with IHIO has been reported to have protective effects in patients undergoing liver resection. The role of IHIO, however, has not been fully elucidated in donors and recipients during living donor liver transplantation.

Study Overview

• Status: Unknown
• Conditions: End Stage Liver Disease; Living Donor
• Intervention / Treatment: Procedure: Intermittent hepatic inflow occlusion (IHIO)

Detailed Description

Intermittent hepatic inflow occlusion (IHIO) by clamping of the portal triad, also called Pringle maneuver, is a safe and effective procedure in major hepatectomy in patients with liver disease. IHIO minimizes blood loss and operation time during liver resection. In addition, ischemic preconditioning with IHIO has been reported to have protective effects in patients undergoing liver resection. In the setting of living donor liver transplantation (LDLT), one of the most important concerns is liver donor safety. Several studies have shown the safety of IHIO in donors for liver transplantation (LT). However, the effect of preconditioning with IHIO during donor hepatectomy on LDLT recipients remains unclear. Several small series have assessed the effects on recipients of ischemic preconditioning during whole liver transplantation from deceased donors. The role of IHIO, however, has not been fully elucidated in liver donors and recipients during LDLT. In this randomized, prospective study, we'll evaluate the efficacy of IHIO in the recipients and donors.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Donors and recipient of LDLT, saged ≥18 years, who will undergo LDLT with donors undergoing right hemihepatectomy and recipients receiving right hemiliver grafts
• Informed consent agreement

Exclusion Criteria:

• if the recipients has fulminant hepatic failure
• if the graft to recipient body weight ratio (GRWR) is <0.9
• if a frozen biopsy of the donor liver taken prior to donor hemihepatectomy shows >30% macrovesicular steatosis
• if liver transplantation is ABO incompatible
• if recipients has received previous organ transplants
• if recipients has received or were scheduled to receive multi-organ transplants

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IHIO; Intermittent hepatic inflow occlusion (IHIO) by clamping of the portal triad, minimizes blood loss and operation time during liver resection. In addition, ischemic preconditioning with IHIO has been reported to have protective effects in patients undergoing liver resection. IHIO'll be usually performed 3 times during donor liver parenchymal resection, with each IHIO consisting of clamping of the hepatoduodenal ligament for 15 minutes, followed by reperfusion for 5 minutes.	Procedure: Intermittent hepatic inflow occlusion (IHIO); Intermittent hepatic inflow occlusion (IHIO)'ll be usually performed 3 times during donor liver parenchymal resection, with each IHIO consisting of clamping of the hepatoduodenal ligament for 15 minutes, followed by reperfusion for 5 minutes.
Sham Comparator: Control; The donor liver parenchyma'll be transected without IHIO.	Procedure: Intermittent hepatic inflow occlusion (IHIO); Intermittent hepatic inflow occlusion (IHIO)'ll be usually performed 3 times during donor liver parenchymal resection, with each IHIO consisting of clamping of the hepatoduodenal ligament for 15 minutes, followed by reperfusion for 5 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum alanine aminotransferase (ALT) concentration within 5 days post-operative	The primary end-point of this study is peak serum alanine aminotransferase (ALT) concentration within 5 days post-operation on donors and recipients.	pre-operative and every day till 5 days post-operative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
post-operative clinical courses, such as liver function tests, hospital stay, and morbidity	Secondary end-points in recipients include those involving post-operative clinical courses, such as liver function tests, graft function, stay in the intensive care unit and in-hospital mortality, hospital stay and in donors post-operative clinical courses, such as liver function tests, hospital stay and morbidity requiring additional interveition or delay of hospital stay.	During post-operative 1 months or hospitalization
Serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)- α, and hepatocyte growth factor (HGF)	Blood samples for measurement of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)- α, and hepatocyte growth factor (HGF) will be taken from donors immediately after anesthesia induction and 2 hours after graft removal, and from recipients immediately after anesthesia induction, during the anhepatic phase, 2 hours after reperfusion, and at 1 and 3 days post-operatively.	In donors immediately after anesthesia induction and 2 hours after graft removal, and in recipients immediately after anesthesia induction, during the anhepatic phase, 2 hours after reperfusion, and at 1 and 3 days post-operatively.
Caspase-3 and malondialdehyde in liver biopsy	Biopsy samples'll be taken from donors at the time of laparotomy, just before portal vein and hepatic artery clamping after parenchymal resection, and from recipients two hours after reperfusion. Hepatocyte injury will be determined by measuring the concentrations of caspase-3, and malondialdehyde (MDA) by ELISA.	In donors at the time of laparotomy, just before portal vein and hepatic artery clamping after parenchymal resection, and in recipients two hours after reperfusion

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Investigators: Principal Investigator: Jae-Won Joh, MD., PhD, Samsung Medical Center

Publications and helpful links

General Publications

• Park JB, Joh JW, Kim SJ, Kwon CH, Chun JM, Kim JM, Moon JI, Lee SK. Effect of intermittent hepatic inflow occlusion with the Pringle maneuver during donor hepatectomy in adult living donor liver transplantation with right hemiliver grafts: a prospective, randomized controlled study. Liver Transpl. 2012 Jan;18(1):129-37. doi: 10.1002/lt.22409.

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): June 1, 2010
• Study Completion (Anticipated): August 1, 2010

Study Registration Dates

• First Submitted: July 27, 2010
• First Submitted That Met QC Criteria: July 27, 2010
• First Posted (Estimate): July 28, 2010

Study Record Updates

• Last Update Posted (Estimate): July 28, 2010
• Last Update Submitted That Met QC Criteria: July 27, 2010
• Last Verified: July 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Liver Diseases; End Stage Liver Disease
• Other Study ID Numbers: 2007-09-096