AJT Report: Living Donor Liver Transplants Poised for a Comeback?

[Clark]

http://onlinelibrary.wiley.com/doi/10.1111/ajt.13609/full

The AJT Report
Sue Pondrom
DOI: 10.1111/ajt.13609
American Journal of Transplantation
Volume 15, Issue 12, pages 3015–3016, December 2015
Currently, there are plans by many transplant centers in the United States to increase the number of living donor liver transplants (LDLTs), according to the United Network for Organ Sharing (UNOS). While the number of LDLTs ranged from 219 to 288 per year in the past 10 years, the country is on track to perform nearly 350 in 2015. However, the U.S. still lags far behind Asian countries.

Why did the U.S. fall behind eastern nations? What has changed to improve the rates of LDLTs in the U.S.? How is the international community responding to the country's current efforts?

A Climate of Risk Aversion
Adult-to-adult LDLT was popularized in the 1990 s. In 2001, 524 adult-to-adult LDLTs were performed in the U.S., according to UNOS. That number decreased to 362 in 2002, and fell to a low of 218 by 2008. The climate of risk aversion can be traced to changes in allocation and publicity about donor deaths between 2000 and 2010.
The 2002 implementation of the Model for End-Stage Liver Disease (MELD) scoring system provided exception points that allowed many patients with hepatocellular carcinoma (HCC) to receive deceased donor (DD) transplants, rather than finding live donors.

“When adult-to-adult LDLT first began in the U.S., there was great enthusiasm for transplant centers to start an LDLT program, whether they needed to or not,” says Elizabeth Pomfret, MD, PhD, chair at the Lahey Clinic Department of Transplantation and Hepatobiliary Diseases in Burlington, Mass., and past president of the International Liver Transplantation Society. Initially, she says, there were reports of great outcomes and very few complications. “That was clearly not the case,” she adds. “When the donor deaths occurred, they left the transplant community reeling. The small but ever-present risk to the donor could not be more apparent, and that significantly dampened the enthusiasm for LDLT in western countries with access to deceased donor liver transplantation (DDLT).”

According to James Trotter, MD, medical director of liver transplantation at Baylor University Medical Center in Dallas, the current system of allocation is based on death as a primary metric. “But there are things worse than death,” he says. “One of those is being completely nonfunctional with chronic liver disease and having no hope for transplant. I think all those forces are pushing people to look at this.”

Poised for an Upsurge
“I think changes in the U.S. allocation policies may stimulate LDLTs,” says Sandy Feng, MD, PhD, professor of transplant surgery at the University of California, San Francisco. “With the recent adoption of Share 35, the disease severity at transplant has increased significantly in areas of the country that had a relative excess of deceased donor livers and were transplanting at lower disease severity. A reduction in availability of deceased donor organs may stimulate more centers and their patients to consider LDLT as a solution.”

KEY POINTS
   •   Many U.S. transplant centers plan to increase the number of LDLTs they perform.
   •   Previously, the risk to the donor significantly dampened the enthusiasm for LDLT in western countries with access to deceased donor liver transplantation.
   •   As improved procedures have developed, a subsequent rise in the number of LDLTs performed has followed.
   •   Some advocate for a few high-volume centers to perform LDLTs in the U.S., rather than a large number of lower volume centers.

Similarly, beginning in October 2015, UNOS modified the maximum value of exception scores for patients with HCC to create a “better balance in transplant opportunities” between candidates with HCC exceptions and those with allocation priority based on their calculated MELD/Pediatric End-Stage Liver Disease (PELD) score. The reduced access to deceased donor livers for HCC patients may increasingly motivate centers and patients to pursue LDLT for HCC.

Dr. Trotter recently received a call from an institution at which surgeons were considering an LDLT program. Previously, patients with cancer at the institution had only a three- to six-month wait, but with the new policies, they won't get an upgrade on their MELD score for six months.

Another major contributor to the rise in LDLTs is improved procedures. “For the first time since adult LDLT began in the U.S., we are seeing many new programs starting up,” Dr. Pomfret says. She is concerned, however, that “some of the new centers might not have the necessary ‘field strength’ to start adult LDLT programs, as evidenced by several recent near-miss events and serious donor and recipient complications.”

Donor Safety
After some of the deaths, the transplant community and regulators focused on donor safety, creating donor advocacy teams and improving informed consent, says Charles Miller, MD, director of liver transplantation at the Cleveland Clinic. He and his colleagues set up a focus group of interested surgeons and nurses and allowed them to work on the topic both clinically and academically. “We also created a crisis plan,” he added. “I think the real understanding is not if, it's when a disaster happens.” In 2002, Dr. Miller led a transplant team at Mt. Sinai in New York through a donor death.
Dr. Miller was the editor of the International Liver Transplantation Society practice guidelines for LDLT, which he presented at the organization's 2014 annual meeting. He notes that in most instances, a right lobe is needed for an adult transplant. However, for donor safety reasons, left lobe LDLT is pursued whenever possible. “We think using the donor's left lobe is probably safer,” says John Roberts, MD, chief of the division of transplantation at the University of California, San Francisco. “As far as I know, there's never been a left lobe donor who's needed a transplant, but some right lobe donors have.” He adds that he appreciates the flexibility of matching donor size to recipient size (see “UCSF: A Growing Program,” below).

With right and left lobes, donors have two good options to choose from, Dr. Miller says. “There is a differential risk between right and left lobes for both donor and recipient. Everyone would like to err on the side of donor safety with a left lobe as long as there is good expectation for success in the recipient, and we are learning more and more how to use left lobes successfully.”

International Opinion
Asia has long been a leader in LDLT. “The AJT Report” contacted several liver surgeons to ask their opinion of the current upsurge in LDLT in the U.S.

Looking back at the history of LDLT in the U.S., Sung-Gyu Lee, MD, of the Asan Medical Center in Seoul, South Korea, and an international leader in LDLT, says that donor safety guidelines of keeping resection to no more than 70% in the donor were ignored in the U.S., and that donor surgeon inexperience contributed to the disasters.

Yaman Tokat, MD, with the Florence Nightingale Organ Transplant Center in Istanbul, Turkey, recommends that a few experienced centers perform LDLT in the U.S., as opposed to each center attempting to perform two or three a year. “Otherwise,” he adds, “no experience will be gathered.” His center performs 110 to 130 liver transplants a year, 80% to 90% of which are LDLTs.

In Japan, the number of LDLTs performed is approximately 350 to 400 per year, according to Hiroto Egawa, MD, who is with Kyoto University Hospital in Kyoto, Japan. He says many U.S. and European surgeons have visited his center and that of Dr. Lee in South Korea. He noted that only “surgeons who have tremendous skills” should do LDLTs in the U.S.

Arvinder S. Soin, MD, at the Medanta Institute of Liver Transplantation and Regenerative Medicine in Gurgaon, Haryana, India, echoes the importance of high-volume centers. “Having gone through years of DDLT and hepatobiliary practice earlier, and now nearly 2,000 LDLTs over the past 10 years, it is clear to me that neither DDLT nor standard hepatobiliary surgery prepares a surgeon adequately for all the complexities of LDLT.” He suggests that an experience of at least 200 LDLTs is needed during a surgeon's training period. “Furthermore,” he adds, “they should aim at a case volume of at least 25 LDLTs a year to maintain the expertise.”

UCSF: A GROWING PROGRAM
This year, John Roberts, MD, expects the University of California, San Francisco (UCSF) to perform approximately 30 LDLTs. The model at UCSF has been the Multi Organ Transplant Program at University Health Network in Toronto. He's also doing his best to use the safer left lobe from the donor when possible.
As Gary Levy, MD, does in his Toronto program, UCSF hepatologists first speak with each liver candidate, telling them about their risk of death* and the possibility of LDLT as an option. Patients are told about a website they can refer friends and family to. In a nonconfrontational manner, the website explains living donation and offers readers a chance to fill out a questionnaire citing their interest in donating and their health history. “Some patients find it difficult to speak to potential donors. The website has made that process much easier,” says Dr. Roberts.
When UCSF receives the questionnaire, they refer the potential donor to a nearby, local lab for blood work. Some never get the blood work, but for those who do, the chances of a becoming a live donor are greatly increased. Once the patient comes to UCSF, a determination is made whether a left lobe can be used, or if it should be the right.
Dr. Levy says his program in Toronto performs 65 to 75 LDLTs each year. The numbers are increasing, resulting in a lower death rate among listed patients. Prior to initiating LDLT it was 35%,” he says. “Now, that has dropped to 18%.”