Organ monitoring and identification of ischemic liver injury during ex situ porcine liver machine perfusion-A randomized controlled study

Abstract

The global shortage of donor livers has led to an increased reliance on extended-criteria donor livers, including those from donors after circulatory death. Utilizing marginal livers necessitates distinguishing between injured but recoverable livers and those that are irreversibly damaged. Bile duct injury, prevalent in these grafts, poses significant risks, as ischemic injuries can be challenging to assess and may lead to recipient bile duct strictures and ultimately graft failure. This study aimed to identify objective measurements that enhance existing viability criteria and facilitate the diagnosis of ischemic injuries. We employed ex situ machine perfusion (MP) to monitor porcine livers subjected to standardized biliary injury (BileINJ), standardized global liver injury (GlobalINJ), and no injury (CTRL, total n=23). Using microdialysis catheters and pCO 2 sensors, we analyzed liver tissue, hilar plate, and bile duct, in addition to standard viability assessments, collecting data on 77 variables. Principal component analysis indicated distinct clustering of the GlobalINJ and partially the BileINJ group away from the CTRL group during MP. Feature extraction models highlighted microdialysate lactate, lactate/pyruvate ratio, glycerol, tissue pCO 2 , and blood gas hematocrit as critical indicators for classifying liver state. Histopathological evaluations confirmed group-specific liver and bile injuries. We identified unique metabolic patterns that differentiate ischemically injured from non-injured porcine livers and were able to distinguish liver and biliary injury. Real-time monitoring of livers using microdialysis and tissue pCO 2 during MP is feasible and clinically available. Measurements taken in the hilar plate show the ability to identify bile duct damage while not introducing measurement devices to the vulnerable bile duct itself. Our findings enable more objective and timely selection of transplantable livers and warrant further investigation in clinical studies.

Keywords: functional assessment; ischemia reperfusion injury; liver function; liver transplantation; machine perfusion; organ preservation; organ transplantation.