Literature
Clinical Pearls & Morning Reports
Published November 15, 2023
What strategies are currently used to expand the pool of available livers for transplantation?
In the United States, the Model for End-Stage Liver Disease (MELD) score, or the complementary Pediatric End-Stage Liver Disease (PELD) score for children under the age of 12 years, has been used since 2002 to assess the need for a liver transplant. Read the NEJM Review Article here.
Clinical Pearls
Q: What are the predominant indications for liver transplantation in high-income countries?
A: Since the introduction of direct-acting antiviral therapies in high-income countries, there has been a precipitous decline in the number of patients placed on the waiting list because of hepatitis C virus (HCV) infection, and alcohol-associated liver disease and metabolic dysfunction–associated steatotic liver disease, formerly called non–alcohol-related fatty liver disease, have become the predominant indications for liver transplantation.
Q: Are patients worldwide prioritized for liver transplantation based on the greatest urgency?
A: In the United States, prioritization of patients awaiting transplants from deceased donors is guided by the federal final rule for transplantation, which dictates that transplantation centers must allocate donor livers on the basis of the greatest urgency, while negating inequities based on waiting time or geography and avoiding futile transplantation. The MELD and PELD scores have been the main tools for prioritizing patients on the waiting list. In contrast, in the United Kingdom, deceased-donor livers have been allocated since 2018 according to the anticipated benefit for the patient rather than urgency.
Morning Report Questions
Q: What strategies are currently used to expand the pool of available livers for transplantation?
A: Most deceased-donor livers are from persons receiving life support who have irreversible cerebral and brain-stem injury (declared brain death). One strategy to expand the pool of usable donor livers is the use, in carefully selected circumstances, of organs from deceased donors infected by HCV virus or the human immunodeficiency virus. Another strategy is donation after circulatory death, with death declared on the basis of the cessation of both circulatory and respiratory function in patients who retain brain-stem function, despite severe, irreversible neurologic injury. There is an urgent need to increase the number of livers available for pediatric liver-transplant candidates, especially infants. Given the ability of the liver to regenerate, one strategy that appears to be helpful is to split a liver from a deceased donor into two allografts, typically with one piece transplanted in a small child and the other in an adult.
Q: What is the current management of donated livers prior to transplantation?
A: The standard of care for more than 30 years has been to flush the organ from a deceased donor with preservation solution at 4°C, in order to reduce cellular metabolic processes, and then to transport the organ to the transplantation site under conditions of static cold storage. Even though static cold storage is effective, continued cold ischemia leads to mitochondrial changes, including decreased cellular respiration and the accumulation of succinate and NADH with concomitant ATP depletion. On reperfusion, reactive oxygen species are released from the mitochondria, leading to further cellular injury. In contrast, machine perfusion before implantation aims to ensure more consistent tissue quality, while extending the preservation time and reducing the discard rate. Machine perfusion of donor livers with oxygenated solutions may mitigate ischemia–reperfusion injury and allow for successful transplantation of higher-risk livers. Two ex vivo machine perfusion strategies currently used are hypothermic machine perfusion and normothermic machine perfusion. Normothermic machine perfusion of the donor liver pumps oxygenated, ABO-compatible blood at 37°C through the hepatic artery and portal vein simultaneously. This approach has led to significant reductions in early allograft dysfunction and ischemic-type biliary strictures, as compared with static cold storage.