For many years, the public has associated organ transplant with an image of a medical professional running, cooler in hand, to transport an organ to a recipient as fast as possible. Though this scenario still exists in liver transplant, a new image has come into view in which transplant professionals do not use cold storage. Instead of a hypothermic process in which livers are flushed and statically stored using cold preservation solution to slow metabolism, livers now can be stored using normothermic machine perfusion (NMP), a so-called liver in a box, in which organs remain alive, oxygenated and metabolically functional in an ex vivo setting.
Cold storage induces some organ injury and progressive cellular function degradation, and in some cases is associated with long-term negative outcomes, including allograft dysfunction and biliary complications. In contrast, NMP pumps warm, oxygenated blood, delivering nutrients and substrate needed for metabolic function.
“This changes organ preservation,” says Amit K. Mathur, M.D., an abdominal transplant surgeon at Mayo Clinic in Arizona. “It leads to functional improvement without the obligatory organ injury that occurs with death and the classic organ recovery process. This pump is designed to mimic physiological perfusion, with blood pumping into arteries much like it occurs in the human body, allowing blood to circulate through the organ with dual arterial and portal venous supply, normal venous return, and recirculation after reoxygenation and nutrient provision. It allows the liver to recover in a normal homeostatic state while on the device, stabilizing the organ. The recipient gets a better liver.”
Dr. Mathur also indicates there is evidence that NMP can lower biliary and hepatocellular injury. The device is especially useful for transplants in which a donor has fatty liver disease, is older or became a donor after circulatory death. The organs in these transplants are more sensitive to such injuries at baseline.
What prompted creation of a liver in a box
Two companies have developed FDA-approved liver NMP devices. Key transplant community concerns prompted its development:
- Many more patients have been listed for transplant than organs have been available — what Dr. Mathur calls a “never-ending demand we’ve not been able to overcome.”
- For patients offered transplant, physicians want to improve and optimize outcomes.
Though the liver in a box is relatively new in the U.S., Dr. Mathur indicates that European groups have used the device clinically for some time and have seen positive results.
Liver in a box benefits, economic challenge
Dr. Mathur notes multiple benefits to the use of NMP devices in liver transplant:
- Expands geographical reach since cold injury is minimized
- Eases logistics of minimizing cold storage
- Makes more transplants possible by optimizing function of donor livers with known risk factors for dysfunction and complications
- Provides easier access to organs for waitlisted patients
Dr. Mathur adds that the device may also be protective for negative immediate or long-term outcomes and may improve livers, in contrast to cold storage.
A potential downside to liver NMP is that it requires increased staff support compared with transplants done without the device. Each use of the device also costs significant money, according to Dr. Mathur.
“We want to increase access and optimize outcomes, but we need to balance the cost factor,” says Dr. Mathur.
Mayo Clinic’s liver in a box involvement
Mayo Clinic participated in one of the two large U.S. trials that studied liver NMP. Observing trial results, Mayo Clinic began using the technology at its Arizona campus in January 2022.
Since Mayo Clinic started using liver NMP, Mayo Clinic in Arizona transplant surgeons have performed more than 40 transplants with it. Mayo Clinic in Florida also has this technology available and has done two transplants. Mayo Clinic in Minnesota is working through the process to use it as well.
Hospital staff reactions to use of liver NMP
Dr. Mathur indicates that staff members have reacted with energy and enthusiasm for the liver NMP system. Multiple Mayo Clinic in Arizona liver transplant surgeons have been trained in the technology, which allows it to be readily available for patients. He also indicates liver transplant anesthesia teams have been positive about the device’s role.
“It’s an incredible challenge in a liver transplant to maintain patient stability,” says Dr. Mathur. “Using the device, anesthetists have observed more physiological stability with fewer transfusions and vasoactive medications needed.”
He also mentions ICU colleagues’ satisfaction with the liver in a box because of patient stability during the perioperative period plus decreased ICU time and, potentially, overall length of stay.
“We are carefully monitoring our outcomes, quality and costs with this technology” he says. “I believe it will prove to be an intelligent investment.”
Though the liver in a box is commercially available, it’s not yet widely disseminated, says Dr. Mathur, indicating that an institution’s successful use of the device requires resources.
Encouragement for referring physicians
While the device can make a significant difference in some liver transplants, surgeons will not necessarily elect to use it in every case. Surgeons choose to use liver in a box versus using it at the request of a patient or referring physician. Dr. Mathur is glad to have the option to use this device when it serves a patient’s situation.
Rather than focus on transplant centers offering liver NMP, physicians considering patient referral should consider other details, suggests Dr. Mathur.
“If you’re looking for a potential liver transplant for a patient, you should look for a place performing transplants at a very high rate and with broad organ acceptance patterns,” he says, indicating that Mayo Clinic fits this profile. These data are publicly available.
For physicians considering Mayo Clinic referral for a liver transplant opinion, he states that they can make referrals feeling comfortable that their patient will receive a timely and safe transplant. Despite high liver transplant waitlist mortality nationwide, Dr. Mathur indicates that Mayo Clinic’s liver transplant waitlist mortality is fairly low.
Dr. Mathur also notes that at Mayo Clinic Transplant Center, use of advanced technologies such as liver NMP is commonplace overall. He indicates that there is potential to increase the center’s transplant rates. The liver perfusion device in particular will help Mayo Clinic Transplant Center achieve its goals and optimize results, he says. Since Mayo Clinic is considered a leader in extended-criteria organ use with suboptimal donor characteristics, this pursuit strongly motivates Mayo Clinic transplant surgeons to continue work with liver NMP