Observations on the ex situ perfusion of livers for transplantation

Abstract

Normothermic ex situ liver perfusion might allow viability assessment of livers before transplantation. Perfusion characteristics were studied in 47 liver perfusions, of which 22 resulted in transplants. Hepatocellular damage was reflected in the perfusate transaminase concentrations, which correlated with posttransplant peak transaminase levels. Lactate clearance occurred within 3 hours in 46 of 47 perfusions, and glucose rose initially during perfusion in 44. Three livers required higher levels of bicarbonate support to maintain physiological pH, including one developing primary nonfunction. Bile production did not correlate with viability or cholangiopathy, but bile pH, measured in 16 of the 22 transplanted livers, identified three livers that developed cholangiopathy (peak pH < 7.4) from those that did not (pH > 7.5). In the 11 research livers where it could be studied, bile pH > 7.5 discriminated between the 6 livers exhibiting >50% circumferential stromal necrosis of septal bile ducts and 4 without necrosis; one liver with 25‐50% necrosis had a maximum pH 7.46. Liver viability during normothermic perfusion can be assessed using a combination of transaminase release, glucose metabolism, lactate clearance, and maintenance of acid‐base balance. Evaluation of bile pH may offer a valuable insight into bile duct integrity and risk of posttransplant ischemic cholangiopathy.

Manipulation of Lipid Metabolism During Normothermic Machine Perfusion: Effect of Defatting Therapies on Donor Liver Functional Recovery

“…It was associated with enhanced mitochondrial functioning, decreased vascular resistances, and reduced markers of hepatocellular injury and inflammation with improved biliary function. These parameters are suggested as being indicative of transplantability for extended criteria donor (ECD) organs undergoing NMP, according to the evidence available to date . Therefore, manipulation of the hepatic lipid metabolism during NMP may defat steatotic organs and increase their functional recovery, potentially halting the harmful effects of reperfusion injury.…”

Pretransplant sequential hypo- and normothermic machine perfusion of suboptimal livers donated after circulatory death using a hemoglobin-based oxygen carrier perfusion solution

“…[1][2][3][4][5] (Dual) hypothermic oxygenated perfusion ([D]HOPE) can be applied to resuscitate the mitochondria and increase hepatic adenosine triphosphate (ATP) content, resulting in less cell injury, including less choliangiocyte injury. [11][12][13] The use of RBC, however, has several drawbacks. 2,6-8 (D)HOPE and NMP may therefore have a complementary effect when applied sequentially.…”

Implementing an innovated preservation technology: The American Society of Transplant Surgeons’ (ASTS) Standards Committee White Paper on Ex Situ Liver Machine Perfusion

“…20 Based on the literature and current knowledge we recommend that the data elements summarized in Table 2 be routinely collected and available through UNet in order to allow accurate assessment of donor quality and permit retrospective review of all posttransplant graft and patient deaths. 20 Based on the literature and current knowledge we recommend that the data elements summarized in Table 2 be routinely collected and available through UNet in order to allow accurate assessment of donor quality and permit retrospective review of all posttransplant graft and patient deaths.…”