Clinical Pearls & Morning Reports
Van Rijn et al. conducted a multicenter, randomized, controlled trial in which patients undergoing transplantation of a liver obtained from a donor after circulatory death received that liver after preservation with hypothermic oxygenated machine perfusion (after static cold preservation during transportation) or conventional static cold storage alone. Read the NEJM Original Article here.
Q: Are nonanastomotic biliary strictures a common complication after liver transplantation?
A: Nonanastomotic biliary strictures are a major complication after liver transplantation, resulting in cholestasis and cholangitis and, frequently, in the use of biliary interventions or even transplantation of a new liver graft. The incidence of nonanastomotic biliary strictures is approximately 3 times as high after the transplantation of livers obtained from donors after circulatory death as after the transplantation of livers obtained from brain-dead donors.
Q: What is a key mechanism in the pathogenesis of nonanastomotic bile duct strictures after liver transplantation?
A: Ischemia–reperfusion injury is a key mechanism in the pathogenesis of bile-duct injury and the subsequent development of biliary strictures after transplantation. Although conventional static cold preservation provides some protection against ischemia–reperfusion injury, more-advanced preservation methods are needed to improve outcomes after transplantation of livers obtained from donors after circulatory death. Oxygenated ex situ machine perfusion is a dynamic preservation method that has been developed to reduce the incidence and severity of ischemia–reperfusion injury and to improve outcomes after organ transplantation. Preclinical studies have shown that a short period (1 to 2 hours) of hypothermic oxygenated machine perfusion restores mitochondrial function and reduces the production of radical oxygen species and damage-associated molecular patterns after transplantation. This relatively simple technique can be performed after static cold storage.
A: In this trial, symptomatic nonanastomotic biliary strictures occurred in 5 of 78 patients (6%) in the machine-perfusion group and in 14 of 78 (18%) in the control group (risk ratio, 0.36; 95% confidence interval [CI], 0.14 to 0.94; P=0.03). Early allograft dysfunction occurred in 20 machine-perfused livers (26% of the patients), as compared with 31 control livers (40% of the patients) (adjusted risk ratio, 0.61; 95% CI, 0.39 to 0.96). There were no relevant differences between the two groups in the use of renal-replacement therapy, in the durations of stay in the intensive care unit or hospital, or in graft and patient survival at 1 year. There was no relevant clinical difference between the two groups in the severity of adverse events.
A: In contrast to normothermic machine perfusion, hypothermic machine perfusion is currently not considered to be a tool for viability testing before transplantation; rather, it is a method to reduce the incidence of ischemia–reperfusion injury. This makes it suited for donor livers with an increased risk of development of ischemia-related complications, such as livers obtained from donors after circulatory death. To this end, hypothermic and normothermic machine perfusion serve different goals and are not competing techniques. The two techniques can be applied sequentially with complementary benefits. Whether hypothermic machine perfusion is also beneficial in the transplantation of livers obtained from brain-dead donors is the subject of ongoing clinical trials.