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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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End Stage Liver Disease, Living Donor

Intervention / Treatment
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* Procedure: Intermittent hepatic inflow occlusion (IHIO)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IHIO<br>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)<br>* 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.<br>|
| Sham Comparator: Control<br>The donor liver parenchyma'll be transected without IHIO. | Procedure: Intermittent hepatic inflow occlusion (IHIO)<br>* 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.<br>|

What is the study measuring?
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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 |