Machine Perfusion Could Help Address Transplant Crisis for Pediatric Liver Diseases

Ahmad Anouti, MD
Credit: UT Southwestern

New data from the North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) 2024 annual meeting sheds new light on the potential of machine perfusion in pediatric liver transplants.

An evolving area of research and policy, with recent data reflecting the benefit of allocation strategies, the data from NASPGHAN 2024 details the effect of machine perfusion among a cohort of 22 pediatric patients, with results indicating use of a machine-perfused marginal graft was not associated with increased mortality in liver transplant patients. However, investigators suggest further investigation is needed to better understand the optimal patient population for this emerging modality.^1,2

“I think this is something to be taken with a grain of salt. When you think about pediatric liver transplantation, you think about the main issue as the shortage—but, there are centers in the US that have no one on the wait list because of living donations. So, the question, for me, becomes: when it comes to machine perfusion or transplanting suboptimal graphs, what's the end goal?,” explained Ahmad Anouti, MD, of the Digestive and Liver Disease, The University of Texas Southwestern Medical Center. “The end goal is to combat this shortage [and] get patients off the waitlist and doing well and machine perfusion is definitely a good alternative. However, if I have the perfect optimal graph, certain kids do not need perfusion.”

With the aforementioned question in mind, Anouti and colleagues from the University of Texas, Case Western Reserve University, and the Mayo Clinic launched a study to better understand characteristics and outcomes of machine-perfused livers among pediatric live transplant recipients in the US. With this in mind, investigators designed their study as an analysis of data recorded within the United Network for Organ Sharing (UNOS) database from January 2016 through April 2024.¹

After performing a search of the UNOS database, investigators identified 22 pediatric patients who received perfused livers. Among this cohort, 81.8% (n=18) had normothermic perfusion and 9.1% (n=2) had hypothermic perfusion. This cohort had a mean age of 7.91±7.04 years, 31.8% were White, and approximately 50% were female. The survival rate among the cohort was 100%.¹

Analysis of cohort characteristics suggested the rate of utilization of machine perfusion increased with time with 4.5% in 2016, 9.1% in 2022, 68.2% in 2023, and 18.2% in 2024. Among the cohort, the leading liver indications for receiving perfused livers were extrahepatic biliary atresia (36.4%), congenital hepatic fibrosis (9.1%), and unspecified cholestatic liver disease (9.1%). Investigators highlighted there were no significant differences in the characteristics between patients received hypothermic and normothermic perfusion.¹

Investigators used logistic regression modeling to assess variables influencing the decision to perfuse livers for pediatric patients. They then applied the Least Absolute Shrinkage and Selection Operator (Lasso) method—a machine learning technique—to identify key predictive variables within the logistic regression model that impacted perfusion decisions. Following the Lasso selection, a gradient boosting decision tree algorithm was employed to determine the relative likelihood importance of each variable in the Lasso regression model.¹

According to instigators, this statistical approach allowed for an evaluation of each variable's influence in relation to others within the predictive framework. In addition to these analyses, investigators pointed out an additional sensitivity analysis was performed to compare the characteristics of hypothermic and normothermic perfused pediatric patients.¹

Upon analysis, results indicated top volume (Odds Ratio [OR], 3.74, 95% CI, 3.19 to 4.38) and middle volume (OR, 2.61; 95% CI, 2.26 to 3.01) centers had a significantly increased association with utilizing machine perfusion for pediatric livers relative to low volume centers. Further analysis found significant increases in association with machine perfusion among the latest transplant era (09/2021 through 2024) (OR, 14.43; 95% CI, 12.89 to 16.19) and with donation after circulatory death (OR, 7.68; 95% CI, 6.99 to 8.44).¹

Using their decision tree model, investigators determined transplant era (47.4%), donation after circulatory death (25.2%), top (4.7%) and middle (2.2%) volume centers had the highest importance of likelihood to impact the decision for perfusion. Investigators pointed out, when accounting for these variables, the modeling tree returned an area under the curve of 0.91, a sensitivity of 66.6%, and a specificity of 96.4% for assessing the likelihood of perfusion among pediatric patients.¹

“I think key point is, again, do not shy away from machine perfusion, but it is not for everybody,” Anouti added.

References:

1. Anouti A, Dahshi H, Heimbach J, Cotter T, Hassan S. ADVANCEMENTS IN PEDIATRIC LIVER TRANSPLANTATION: THE ROLE OF MACHINE PERFUSION Presented at NASPHGAN 2024 in Hollywood, Florida, from November 7 – November 9, 2024.
2. Derman C. Policy changes boost survival in pediatric liver transplants. HCP Live. October 18, 2024. Accessed November 9, 2024. https://www.hcplive.com/view/policy-changes-boost-survival-in-pediatric-liver-transplants.