Failure to Rescue Pediatric Recipients of Living Donor Liver Transplantation: A Single-Center Study of Technical Complications in 500 Primary Grafts.

BACKGROUND: The concept of failure to rescue (FTR) has been used to evaluate the quality of care in several surgical specialties but has not been well-studied after living donor liver transplantation (LDLT) in children. METHODS: This study retrospectively reviewed 500 pediatric LDLT performed at a single center between 1993 and 2022. The recipient outcomes were assessed by means of patient and graft survival rates, retransplantation rates, and arterial/portal/biliary complication rates. Graft and patient losses secondary to these complications were calculated regarding FTR for patients (FTRp) and grafts (FTRg). RESULTS: Overall 1- and 5-year patient survival rates were 94.5% and 92.1%, respectively, the corresponding figures for graft survival being 92.7% and 89.8%. One-year hepatic artery complication rate was 3.6% (n = 18 cases), the respective rates for portal vein complications and biliary complications being 5.7% (n = 57) and 15.6% (n = 101). One-year FTRp rates for hepatic artery thrombosis, portal vein thrombosis, anastomotic biliary stricture, and intrahepatic biliary stricture were 28.6%, 9.4%, 3.6%, and 0%, respectively. The corresponding FTRg rates being 21.4%, 6.3%, 0%, and 36.4%. CONCLUSION: Such novel analytical method may offer valuable insights for optimizing quality of care in pediatric LDLT.

Premature senescence of the liver in Alagille patients.

INTRODUCTION: Alagille syndrome (ALGS) is an autosomal dominant disease characterized by a multisystem involvement including bile duct paucity and cholestasis, caused by JAG1 or NOTCH2 mutations in most of the cases. Jagged1-Notch2 interactions are known to be crucial for intrahepatic biliary tract development, but the Notch signaling pathway is also involved in the juxtacrine transmission of senescence and in the induction and modulation of the senescence-associated secretory phenotype (SASP). AIM: Our aim was to investigate premature senescence and SASP in ALGS livers. METHODS: Liver tissue from ALGS patients was prospectively obtained at the time of liver transplantation (n = 5) and compared to control livers (n = 5). RESULTS: We evidenced advanced premature senescence in the livers of five JAG1 mutated ALGS pediatric patients through increased senescence-associated beta-galactosidase activity (p<0.05), increased p16 and p21 gene expression (p<0.01), and increased p16 and γH2AX protein expression (p<0.01). Senescence was located in hepatocytes of the whole liver parenchyma as well as in remaining bile ducts. The classical SASP markers TGF-ß1, IL-6, and IL-8 were not overexpressed in the livers of our patients. CONCLUSIONS: We demonstrate for the first time that ALGS livers display important premature senescence despite Jagged1 mutation, underlying the complexity of senescence and SASP development pathways.

Nasobiliary drainage prior to surgical biliary diversion in progressive familial intrahepatic cholestasis type II.

Progressive familial intrahepatic cholestasis (PFIC) can cause intense pruritus that is refractory to medical therapy. Surgical biliary diversion techniques, including partial internal biliary diversion (PIBD), have been developed over the years to relieve pruritus without requiring liver transplantation. No clinical or genetic features can currently predict postoperative pruritus response. We present three PFIC type 2 (PIFC 2) patients who underwent transient endoscopic nasobiliary drainage (NBD) prior to PIBD surgery. Two patients repeatedly responded to NBD and presented with complete pruritus resolution after subsequent PIBD. NBD failed technically in the third patient, and PIBD was partially successful. Mild post-endoscopic biological pancreatitis occurred in 2/6 NBD procedures and resolved spontaneously. The only adverse effect observed within 7 years post-PIBD was very mild transient osmotic diarrhea.Conclusion: Our limited data suggest that NBD is a safe and effective way to predict pruritus response before performing permanent biliary diversion surgery in PFIC patients. What is Known: • Surgical biliary diversion techniques have been developed to relieve intractable pruritus in progressive familial intrahepatic cholestasis (PFIC). • No clinical or genetic features can currently predict pruritus response to surgery. What is New: • Our data suggest that nasobiliary drainage could be a safe and effective tool to predict pruritus response to biliary diversion and avoid unnecessary surgery in PFIC patients.