Another promising medical trial that could save lives thanks to genetically modified pigs: The FDA has given a select group of companies permission to use modified pig livers as a dialysis-like treatment for people with liver failure.

The process would involve circulating a patient’s blood through the pig liver to help clean the blood of contaminants, excess fluids and waste products to improve or stabilize the health of a patient. The clinical trial would include up to 20 patients who don’t qualify for a liver transplant.

UNOS Chief Medical Officer and former liver transplant surgeon Dr. Andrew Klein says this new advancement is based on a treatment that was first used in the 1970s called xenoperfusion. He spoke recently about what this new FDA trial could mean for saving lives.

How does this compare to a kidney dialysis machine?

Dr. Klein: One of the things that distinguishes a liver transplant from a kidney transplant, which happens more frequently, is in most cases with kidney failure, there are other therapies which can take over the kidney’s function for a period of time, such as dialysis. You don’t really have anything that could take over liver function aside from a new liver. That’s what this new development is trying to become, a sort of dialysis function for people experiencing liver failure.

Do you have experience with xenoperfusion?

Dr. Klein: In 1993 or 1994, I had a patient at John’s Hopkins, a woman who had acute liver failure, was comatose, and was listed as a candidate for a liver transplant. We didn’t have an organ available, but I had a young surgeon working with me who recalled xenoperfusion from the 1970’s as a viable potential treatment for this patient.

So, we got in touch with a farm that housed pigs in an appropriate way for research and went through a whole process. We got consent, procured a liver from the pig, brought it up to the ICU and started the process of perfusing the patient’s blood through the pig liver and then returning it to the patient.

Within 20 minutes, the patient woke up out of her coma and she improved clinically for a number of hours. Eventually the pig liver deteriorated but the good news is we got extra time to find a liver transplant for her. She was transplanted with a donated (human) liver, and she survived and went home.

So, this treatment is not entirely new, but what probably makes it novel and perhaps more durable is the fact that they’re using genetically modified pigs.

How could this be applied to patients today?

Dr. Klein: Two applications come to mind immediately. It could serve as a bridge to transplant, buying a patient time while transplant teams wait for a viable donated organ to become available. It could also be used as a standalone treatment that makes transplantation not necessary, giving the patient’s liver time to regenerate a certain amount and resume functions.

The companies running the FDA trial will need to determine what functions will be restored by this dialysis, will the treatment act as a liver cleanse, removing the body of toxins and waste products, and/or will it restore synthetic functions, such as resupplying the body with substances livers normally produce? I am really intrigued by this second potential application; it could be something that saves someone from being on the transplant waitlist entirely.

Positive results from this FDA trial could mean another step towards saving the lives of patients experiencing organ failure. Read how UNOS is building technology to connect patients with lifesaving organs and how else doctors are using genetically modified animals to save lives.

As more than 100,000 people await transplant, Donation after Circulatory Death (DCD) plays a significant role in our nation’s donation and transplant system. Last year, more than 7,200 DCD donors made up 43 percent of all deceased donors.

DCD refers to the recovery of organs from a patient who has died due to the irreversible loss of circulatory and respiratory function — when the heart has stopped beating and cannot be restarted. This is distinct from Donation after Brain Death (DBD), where death is declared based on irreversible loss of brain function. Both definitions of death are recognized under the Uniform Determination of Death Act (UDDA), which has guided state laws for over 40 years.

Typically, DCD is an option after a patient has suffered a catastrophic neurologic injury but does not meet the medical criteria for brain death.

The first step in the DCD process is the determination by the patient’s doctor that continued life-sustaining support of circulatory and lung function for this patient is futile, is not in the patient’s best interest, and that it should be withdrawn. If the patient’s doctor makes that determination according to their medical training and judgement, the doctor discusses withdrawing life-sustaining care with the patient’s legal next of kin.

It is important to note that individuals from the organ procurement organization (OPO), the organ recovery team, and the transplant team may not participate in the discussions or the decisions to withdraw life-sustaining care from a patient. Only after the next of kin has consented to withdraw care may members of the OPO enter into discussions with the next of kin to consider the option of organ donation if the patient dies after care is withdrawn.

If the next of kin want to pursue the option of organ donation, they must give consent to do so. The decision to withdraw care must occur before any discussions about consent to donate organs.

If the next of kin decide to withdraw care, the patient is typically moved to an operating room by the hospital nursing staff, where the patient’s doctor directs the hospital nursing staff to disconnect the patient from artificial ventilatory support. As the patient’s blood pressure and blood oxygenation levels fall, different organs will tolerate different periods of oxygen deprivation. After a patient’s heart has stopped beating, the treating physician makes the determination that the patient has suffered circulatory death. Circulatory death determination varies between states and hospitals but generally there is a requirement for 2-5 minutes of sustained cessation of heartbeat before a person is declared dead. Declaration of death is made solely by the treating physician. Only after death is declared, the OPO and organ recovery team may enter the operating room. At that point, organ recovery begins.

Many transplant centers have adopted a defined acceptable time limit between withdrawal of care and cessation of heartbeat (cardiac asystole) for donated organs to be acceptable for transplantation. If this limit is exceeded, the patient will not be eligible for organ donation. In 30-40% of potential DCD cases, organ donation is cancelled for this reason.

The United Network for Organ Sharing (UNOS) has long served as a federal contractor for the U.S. Health Resources and Services Administration to support the national Organ Procurement and Transplantation Network; however, UNOS has no involvement in death declaration, nor does UNOS create policy or law related to death declaration. UNOS is not a healthcare provider, and as such, does not make any clinical decisions related to patient care or organ donation. UNOS does not provide clinical care, participate in decisions to withdraw life-sustaining treatment or regulate hospitals.

UNOS remains steadfast in its support of improving outcomes for patients and increasing safe access to life-saving organ transplants with our proposed reforms that would strengthen many aspects of the organ donation and transplantation ecosystem both within and outside the purview of the Organ Procurement and Transplantation Network. To read more about these reforms please visit our advocacy agenda and our action agenda.

Andrew Klein is Chief Medical Officer for the United Network for Organ Sharing. He received a bachelor’s degree from Duke University, an M.D. and an MBA from Johns Hopkins University.

Hospitals throughout the United States play vital roles in saving and enhancing lives through organ donation and transplantation. But an individual hospital’s responsibilities can differ, depending on whether it is a donor hospital or a transplant hospital.

Donor hospitals

More than 5,000 hospitals in the United States have the potential to admit and care for people who may become organ donors. These range from small, rural community hospitals to major metro trauma centers – any facility with intensive or advanced acute care capabilities. Potential organ donors may meet medical criteria for donation either via brain death (complete, irreversible loss of brain function) or donation after circulatory death (DCD), occurring and pronounced in a hospital setting.

Donor hospitals are responsible for declaring patient death according to applicable state law and accepted medical practice. In addition, all donor hospitals must comply with state and federal laws and regulations regarding identification and referral of potential organ donors to their assigned organ procurement organization (OPO). In general, donor hospitals are overseen by the Centers for Medicare & Medicaid Services (CMS). CMS provides regulations, including conditions of participation, that apply to all hospitals seeking Medicare reimbursement.

Donor hospitals are not members of the national Organ Procurement and Transplantation Network (OPTN) and are not subject to OPTN policies and requirements unless they are also a transplant hospital. The national OPTN, overseen by the federal Health Resources and Services Administration (HRSA), does not have policies governing donor hospitals. The OPO managing the logistics of the donation process is, however, accountable to CMS requirements and to OPTN policies and bylaws.

Transplant hospitals

There are 251 hospitals in the United States accredited to perform transplants of at least one organ type. Each of these hospitals is accountable to state and federal standards for quality of patient care and ensuring patient safety. CMS has a number of applicable regulations and conditions of participation that apply specifically to transplant hospitals.

Each transplant hospital must also be a member of the OPTN and must abide by the OPTN policies and bylaws that govern the transplant process and standards for ensuring patient safety.

Can a donor hospital also be a transplant hospital?

Yes, an individual institution can be both a donor and a transplant hospital. As a transplant hospital, it must be an OPTN member and meet the standards the OPTN establishes. But if it is functioning in its donor hospital capacity, there are no additional OPTN standards or requirements that would apply to it.

The majority of donor hospitals in the United States are not OPTN members and would not be compelled to become OPTN members by any law or regulation. However, they remain responsible for all other state or federal requirements that apply to any part of the donation process.

UNOS Chief Medical Officer Dr. Andrew Klein wrote an opinion piece sharing his first-hand experiences as a liver transplant surgeon and his thoughts about how Congress could help address some of the challenges he encountered. Dr. Klein served as the founding director of the Johns Hopkins Comprehensive Transplant Center and the Cedars-Sinai Comprehensive Transplant Center.

Below is the beginning of Dr. Klein’s opinion article. The full article is published in Nephrology News and Issues. Learn more about his recommendations to strengthen the system.