Tailoring allocation policies and improving access to pediatric liver transplantation over a 16-year period

Background: Pediatric liver transplantation (pLT) waiting-list (WL) mortality is still an issue. We analysed the Italian pLT WL to evaluate the intention-to-treat (ITT) success rate and to identify factors influencing success. Methods: All children (<18 years) listed for pLT in Italy during 2002-2018, were included [Era 1 (2002-2007):centre-based allocation; Era 2 (2008-2014):national allocation; Era 3(2015-2018):national allocation+mandatory-split policy]. Results: 1,424 patients [age:2.0 years (IQR:1.0-9.0); weight:12.0 kg (IQR:7-27)] were listed for pLT. Indications included cirrhosis (70.1%), acute liver failure (13.3%), metabolic disease (7.4%), tumour (7.2%) and undetermined (2%). Median WL time was 2 days (IQR:1-5) for status 1 patients and 44 days (IQR:15-120) for non-status 1. 1,302 (91.4%) were transplanted (67.3% with split grafts), while 50 children (3.5%) dropped from WL (2.5% death, 1.0% clinical deterioration). Predictive factors for receiving LT included status 1 (HR:1.66, p=0.001), status 1B (HR:1.96, p=0.016), status 2A (HR:2.15, p=0.024) and each additional point of PELD/MELD score. Children with recipient's weight >25 kg, blood group O or awaiting pLT combined with other organs had less chance to be transplanted. ITT patient survival rates were 90.5% at 1 year and 87.5% at 5 years remaining stable across Eras. Risk factors for ITT survival were re-transplantation (HR:5.83, p<0.001), status 1 (HR:2.28, p=0.006), status 1B (HR:2.90, p=0.014), status 2A (HR:9.12, p<0.001), recipient weight <6 kg (HR:4.53, p< 0.001) and low-volume activity (HR:4.38, p=0.001). Conclusions: In Italy, continuous adaption of pediatric organ allocation policies has produced a unique allocation model. National organ exchange organisation, pediatric prioritisation rules and mandatory-split policy are key factors to maximise the use of donors for pediatric candidates and to minimise WL mortality without compromising outcomes. Impact and implications: Children candidate to pediatric liver transplantation still suffers of high mortality worldwide. During the last decades, in Italy a continuous adaption of organ allocation policies has produced excellent outcomes for children awaiting liver transplantation. The mortality rate of pediatric liver transplant candidates has been minimized to almost zero, mainly using grafts from deceased-donors. Pediatric priorization rules, national organ exchange organization and mandatory-split liver policy resulted in a unique allocation model for pediatric liver transplantation candidates and represent a landmark for the pediatric transplant community.