Long-term ex situ normothermic perfusion of human split livers for more than 1 week

Abstract

Current machine perfusion technology permits livers to be preserved ex situ for short periods to assess viability prior to transplant. Long-term normothermic perfusion of livers is an emerging field with tremendous potential for the assessment, recovery, and modification of organs. In this study, we aimed to develop a long-term model of ex situ perfusion including a surgical split and simultaneous perfusion of both partial organs. Human livers declined for transplantation were perfused using a red blood cell-based perfusate under normothermic conditions (36 °C) and then split and simultaneously perfused on separate machines. Ten human livers were split, resulting in 20 partial livers. The median ex situ viability was 125 h, and the median ex situ survival was 165 h. Long-term survival was demonstrated by lactate clearance, bile production, Factor-V production, and storage of adenosine triphosphate. Here, we report the long-term ex situ perfusion of human livers and demonstrate the ability to split and perfuse these organs using a standardised protocol.

Indocyanine green: A novel marker for assessment of graft quality during ex situ normothermic machine perfusion of human livers

“…We have previously reported, in part, the characteristics and survival of these grafts (Table 1). 6,7,16 In brief, five livers were retrieved through the donation after the brain death (DBD) pathway, and three were retrieved through the donation after the circulatory death (DCD) pathway (Table 1). All livers were deemed unsuitable for clinical use prior to retrieval.…”

“…Unfortunately, graft evaluation by transplantation was not possible in this study because the livers were considered unsuitable for transplantation prior to donor retrieval, and a protocol for transplantation of marginal organs after machine perfusion does not yet exist at our center. However, using our novel protocol for long‐term perfusion of split livers, we were able to evaluate these organs in the long term (>7 days), which improved our understanding of each graft's performance 7 . Further, our best surrogate for organ quality was overall length of organ survival.…”

“…A perfusate consisting of 4 units of packed red cells, 2 units of fresh frozen plasma, 200 mL of 20% albumin, and 1 L of normal saline was prepared. Using our protocol for long‐term perfusion of human split livers, whole livers were perfused at 36°C for 16–24 h and then surgically split into a left lateral segment graft (LLSG) and an extended right graft (ERG), which were then perfused on two separate perfusion machines 6,7,16 . Liver splitting allowed us to assess these organs individually and increase the number of grafts available for assessment.…”

“…Ex situ machine perfusion facilitates the assessment of donor liver quality prior to transplantation and can potentially resuscitate grafts that would otherwise be considered unsuitable 5 . Our group has recently demonstrated the ability to perfuse human livers using ex situ machine perfusion for >7 days under normothermic conditions, which could allow more sophisticated evaluation of these organs prior to transplant 6,7 . However, the markers currently available for assessment of graft viability are limited by differences in perfusion protocols (thus impacting generalisability), lack of long‐term follow‐up to assess biliary complications, and/or prolonged processing which prevents timely transplant decision‐making 5 .…”

Ex Vivo Tissue-Resident Macrophage Replacement Prior to Allogeneic Transplantation

“…Recent advances in normothermic machine perfusion afford time in which a given organ can be altered prior to transplant. In some cases this time window can be more than a week [3].…”