Policy Changes Boost Survival in Pediatric Liver Transplants

Sarah Bangerth, MS

Credit: USC Transplant Lab, Research Team

A recent study led by Children’s Hospital Los Angeles showed that policy changes to prioritize organ transplants for sick children over adults have helped improve the survival of pediatric acute liver failure (PALF).¹

Over the years, the Organ Procurement and Transplantation Network had periodically tweaked its organ allocation policies to prioritize sicker children over adults. Liver transplantation is the only cure for the life-threatening PALF, but some children do not receive a transplant in time due to the lack of suitable organs. This network also worked on expanding the geographic area of donors to make them more readily available.

Investigators, led by Sarah Bangerth, MS, from the division of Abdominal Organ Transplantation and Hepatobiliary Surgery at Keck School of Medicine, University of Southern California, Los Angeles, sought to investigate how Organ Procurement and Transplantation Network’s changes in patient prioritization and organ allocation impacted waitlist mortality and survival after liver transplant among children. The primary endpoints were waitlist mortality and survival post-liver transplantation.

“We realized that nobody had actually studied this,” said Juliet Emamaullee, MD, PhD, FRCSC, FACS, research director at the division of Abdominal Organ Transplantation, in a press release.²

Using the Scientific Registry of Transplant Recipients, the retrospective cohort study included 1495 patients (< 18) with PALF.¹ Participants had a mean age of 5 (IQR, 1 – 11) years. Children were placed on the liver transplant waitlist between January 1989 and December 2020 based on Status 1/1A listing data and inclusion criteria.

The study included 3 eras: era 1 (January 1989 – June 15, 2000), era 2 (June 16, 2000 – February 1, 2012), era 3 (February 2, 2012 – December 2020). The transplant rate increased from era 1 (71.8%) to era 3 (86.6%). Moreover, the number of children on liver transplant waitlist or who died decreased from 1989 to 2020. Participants in the years 2012 – 2020 had the lowest cumulative incidence of waitlist mortality (P < .001).

Liver transplant recipients from 2012 – 2020 were more likely to receive a whole liver (72%; P < .001), with shorter median cold ischemic time (6.5 hours; IQR, 5.3 – 8.2; P < .001). Children are receiving transplants quicker in recent years despite an increase in distance between the donor and recipient hospitals from 1989 – 2000 (median distance in kilometers, 182.9; IQ, 16.5 – 643.0) to 2012 – 2000 (515.7 km; IQR, 108.6 – 1297.8; P < .001).

Donors in 2012 – 2020 were younger (median age: 14 years), shorter (median height: 152 cm), skinnier (median weight: 50 kg), and were more likely to be deceased (95%). Long-term patient and graft survival rates following liver transplantation were the greatest during 2012 – 2020, with statistically significant differences (P < .001 for patient survival and P = .01 for graft survival at 5 years, respectively.

Multivariate analysis revealed that back in 1989 – 2000, being < 2 years old (compared with ≥ 10 years) (subdistribution hazard ratio [sHR], 8.88; 95% CI, 2.11 – 36.49; P = .003), Hispanic (sHR, 0.08; 95% CI, 0.02 – 0.39; P = .002) and a receipt of deceased donor split grafts (compared with whole liver) (sHR, 0.17; 95% CI, 0.05-0.58; P = .005) were linked to a mortality risk following the liver transplant. However, this was all resolved by 2012 – 2000 (P = .34, P = .10, and P = .27, respectively).

Additionally, being younger than < 2 years old (sHR, 11.26; 95% CI, 2.01-63.24; P = .006) was linked to the risk of graft failure in 1989 – 2000 and 2000 – 2012 (sHR, 4.89; 95% CI, 1.56 – 15.30; P = .006), but this was no longer the case in 2012 – 2020 (P = .99).

“Most of the kids that we transplant are under five and so finding size-matched organs is really difficult,” Emamaullee said.² “The reason our center has been so successful is that we have been expansive in our willingness to split adult livers into a segmental graft—called a technical variant graft—to get those small kids transplanted with adult organs.”

Emamaullee recognized the challenge of using adult livers for children due to the size variation. Allocation policy changes allowed transplant centers to be more likely to get younger, smaller donors from a wider geographic area, making it possible for children to be better matched with an organ their size. However, split-liver grafts have improved over the years.

“Our study showed that these policy changes were associated with substantially decreased deaths on the pediatric waitlist, increased rates of liver transplant, and improved post-transplant outcomes,” Emamaullee said.

References

1. ^{Bangerth S, Vijayendra S, Ascher-Bartlett J, Etasami K, Kohli R, Emamaullee J. Strategic Changes in Organ Allocation Policy and Outcomes in Pediatric Acute Liver Failure. JAMA Surg. Published online October 02, 2024. doi:10.1001/jamasurg.2024.4085}
2. ^{Study shows changes to organ allocation policy reduced waiting time and increased transplants for children with pediatric acute liver failure. EurekAlert! October 2, 2024. https://www.eurekalert.org/news-releases/1060061.Accessed October 15, 2024.}