Long-term outcome of combined radiologic and surgical strategy for the management of biliary complications after pediatric liver transplantation.

OBJECTIVES: We aimed to analyze the risk factors for management failure of BC after pediatric liver transplantation (pLT) by retrospectively analyzing primary pLT performed between 1997 and 2018 (n = 620 patients). RESULTS: In all, 117/620 patients (19%) developed BC. The median (range) follow-up was 9 (1.4-21) years. Patient survival at 1, 5 and 10 years was 88.9%, 85.7%, 84.4% and liver graft survival was 82.4%, 77.4%, and 74.3% respectively. Graft not patient survival was impaired by BC (p = 0.01). Multivariate analysis identified the number of dilatation courses > 2 (p = 0.008), prolonged cold ischemia time (p = 0.004), anastomosed multiple biliary ducts (p = 0.019) and hepatic artery thrombosis (p = 0.01) as factors associated with impaired graft survival. The number of dilatation courses > 2 (p < 0.001) and intrahepatic vs anastomotic stricture (p = 0.014) were associated with management failure. Thus, repeated (> 2) radiologic dilatation courses are associated with impaired graft survival and management failure. Overall, graft but not patient survival was impaired by BC.

Variability of Care and Access to Transplantation for Children with Biliary Atresia Who Need a Liver Replacement.

Background & Aims: Biliary atresia (BA) is the commonest single etiology indication for liver replacement in children. As timely access to liver transplantation (LT) remains challenging for small BA children (with prolonged waiting time being associated with clinical deterioration leading to both preventable pre- and post-transplant morbidity and mortality), the care pathway of BA children in need of LT was analyzed­from diagnosis to LT­with particular attention to referral patterns, timing of referral, waiting list dynamics and need for medical assistance before LT. Methods: International multicentric retrospective study. Intent-to-transplant study analyzing BA children who had indication for LT early in life (aged < 3 years at the time of assessment), over the last 5 years (2016−2020). Clinical and laboratory data of 219 BA children were collected from 8 transplant centers (6 in Europe and 2 in USA). Results: 39 patients underwent primary transplants. Children who underwent Kasai in a specialist -but not transplant- center were older at time of referral and at transplant. At assessment for LT, the vast majority of children already were experiencing complication of cirrhosis, and the majority of children needed medical assistance (nutritional support, hospitalization, transfusion of albumin or blood) while waiting for transplantation. Severe worsening of the clinical condition led to the need for requesting a priority status (i.e., Peld Score exception or similar) for timely graft allocation for 76 children, overall (35%). Conclusions: As LT currently results in BA patient survival exceeding 95% in many expert LT centers, the paradigm for BA management optimization and survival have currently shifted to the pre-LT management. The creation of networks dedicated to the timely referral to a pediatric transplant center and possibly centralization of care should be considered, in combination with implementing all different graft type surgeries in specialist centers (including split and living donor LTs) to achieve timely LT in this vulnerable population.

Features of Nodules in Explants of Children Undergoing Liver Transplantation for Biliary Atresia.

(1) Background: In patients with biliary atresia (BA) liver nodules can be identified either by pre-transplant imaging or on the explant. This study aimed to (i) analyze the histopathology of liver nodules, and (ii) to correlate histopathology with pretransplant radiological features. (2) Methods: Retrospective analysis of liver nodules in explants of BA patients transplanted in our center (2000−2021). Correlations with pretransplant radiological characteristics, patient age at liver transplantation (LT), time from Kasai hepatoportoenterostomy (KPE) to LT, age at KPE and draining KPE. (3) Results: Of the 63 BA-patients included in the analysis, 27/63 (43%) had nodules on explants. A majority were benign macroregenerative nodules. Premalignant (low-grade and high-grade dysplastic) and malignant (hepatocellular carcinoma) nodules were identified in 6/63 and 2/63 patients, respectively. On pretransplant imaging, only 13/63 (21%) patients had liver nodules, none meeting radiological criteria for malignancy. The occurrence of liver nodules correlated with patient age at LT (p < 0.001), time KPE-LT (p < 0.001) and draining KPE (p = 0.006). (4) Conclusion: In BA patients, pretransplant imaging did not correlate with the presence of liver nodules in explants. Liver nodules were frequent in explanted livers, whereby 25% of explants harboured malignant/pre-malignant nodules, emphasizing the need for careful surveillance in BA children whose clinical course may require LT.

Effect of Centralization on Surgical Outcome of Children Operated for Liver Tumors in Switzerland: A Retrospective Comparative Study.

BACKGROUND: Pediatric liver surgery is complex, and complications are not uncommon. Centralization of highly specialized surgery has been shown to improve quality of care. In 2012, pediatric liver surgery was centralized in Switzerland in one national center. This study analyses results before and after centralization. METHODS: Retrospective monocentric comparative study. Analysis of medical records of children (0-16 years) operated for any liver tumor between 1 January 2001 and 31 December 2020. Forty-one patients were included: 14 before centralization (before 1 January 2012) and 27 after centralization (after 1 January 2012). Epidemiological, pre-, intra-, and post-operative data were collected. Fischer's exact and t-test were used to compare groups. RESULTS: The two cohorts were homogeneous. Operating time was reduced, although not significantly, from 366 to 277 min. Length of postoperative stay and mortality were not statistically different between groups. Yet, after centralization, overall postoperative complication rate decreased significantly from 57% to 15% (p = 0.01), Clavien > III complications decreased from 50% to 7% (p < 0.01), and hepatic recurrences were also significantly reduced (40% to 5%, p = 0.03). CONCLUSION: Centralization of the surgical management of liver tumors in Switzerland has improved quality of care in our center by significantly reducing postoperative complications and hepatic recurrence.

Cholangitis Definition and Treatment after Kasai Hepatoportoenterostomy for Biliary Atresia: A Delphi Process and International Expert Panel.

(1) Background: Acute cholangitis during the first year after Kasai hepatoportoenterostomy (HPE) has a negative impact on patient and native liver survival. There are no consistent guidelines for the definition, treatment, and prophylaxis of cholangitis after HPE. The aim of this study was to develop definition, treatment, and prophylaxis guidelines to allow for expeditious management and for standardization in reporting. (2) Methods: the Delphi method, an extensive literature review, iterative rounds of surveys, and expert panel discussions were used to establish definition, treatment, and prophylaxis guidelines for cholangitis in the first year after HPE. (3) Results: Eight elements (pooled into two groups: clinical and laboratory/imaging) were identified to define cholangitis after HPE. The final proposed definitions for suspected and confirmed cholangitis are a combination of one element, respectively, two elements from each group; furthermore, the finding of a positive blood culture was added to the definition of confirmed cholangitis. The durations for prophylaxis and treatment of suspected and confirmed cholangitis were uniformly agreed upon by the experts. (4) Conclusions: for the first time, an international consensus was found for guidelines for definition, treatment, and prophylaxis for cholangitis during the first year after Kasai HPE. Applicability will need further prospective multicentered studies.

Impact of length of donor ICU stay on outcome of patients after pediatric liver transplantation with whole and ex situ split liver grafts.

BACKGROUND: Patients who have a prolonged stay in the intensive care unit (ICU) are often excluded for organ donation because of supposed deleterious effects of a lengthy ICU stay. We aimed to determine the effects of a prolonged donor stay in the ICU on the outcome of liver transplantation (LT) in children. METHODS: Retrospective review of 89 pediatric LT patients, age 0-18 years, period 2003-2018, including patients having undergone whole organ or in situ split LT. The patients were divided into two groups according to the donor length of stay in the ICU. A prolonged stay was defined as >5 days. Recipient, graft, and donor characteristics were compared; outcome parameters included recipient and graft survival rates and postoperative complications. RESULTS: Group short (donor ICU stay <5 days) included 75 patients, group long (donor ICU stay >5 days) 14 patients. Baseline characteristics between recipients did not differ. Donors in group long had significantly more infectious complications and a higher gamma glutamyl transferase (gGT) the day of organ recovery. Incidence of biliary complications post-LT was significantly higher in group long (p = .029). Patient and graft survival rates did not differ significantly between groups. CONCLUSIONS: Donors with a prolonged stay in the ICU should still be considered for liver donation if they fulfill most other selection criteria. Recipients from donors having stayed in ICU >5 days may be at increased risk of biliary complications.

Perioperative Complications after Kasai Hepatoportoenterostomy: Data from the Swiss National Biliary Atresia Registry.

INTRODUCTION: Hepatoportoenterostomy (HPE) is the first-line treatment for biliary atresia (BA) patients. This study aims to describe perioperative complications after HPE and to analyze their impact on outcome. MATERIALS AND METHODS: Patients with HPE (Swiss National Biliary Atresia Registry, 1994-2017) were retrospectively analyzed. Perioperative complications were defined as complications occurring up to 30 days after surgery. Surgical complications were defined as directly related to the surgical act; medical complications were defined as any other deviation from the uneventful postoperative course. RESULTS: Sixty-two patients were included. Median age at HPE was 63 days (18-126). Twenty six patients out of 62 (42%) had ≥ 1 complications: 6/62 (10%) surgical, 24/62 (39%) medical, that is, we observed 7 surgical and 28 medical complications. As for medical complications, cholangitis was the most frequent: 19/28 (68%). Lower gestational age at birth correlated with more overall complications (p = 0.02). Age, weight at HPE, syndromic BA, and postoperative steroid administration were not significantly correlated. There were no perioperative deaths. Perioperative complications did not correlate with overall survival (p = 0.14) and survival with native liver (p = 0.55). CONCLUSION: HPE is often associated with perioperative medical complications. Lower gestational age at birth was significantly associated with more complications. Perioperative complications had no impact on overall outcome.

International survey on anticoagulation and antiplatelet strategies after pediatric liver transplantation.

In pediatric LT, anticoagulants and antiplatelet agents are regularly used to reduce the risk of vascular thrombosis. As evidence for optimal strategy is lacking, local practices vary greatly. The present survey aimed to compile an international overview of anticoagulation and antiplatelet strategies in pediatric LT. An online survey was sent to 98 pediatric LT centers in North and South America, Europe, Asia, and Australia. Twenty-four centers answered the survey. 20/24 (83%) use some sort of anticoagulation and antiplatelet therapy, yielding 20 different strategies. Perioperative vascular problems, size of the hepatic artery, and patient weight were the most frequent determinants of changes in anticoagulant and antiplatelet strategy. Early HAT rates were reported to be 5% or less in 79% of responding centers. Anticoagulation and antiplatelet strategies were not significantly associated with early HAT rates (P = 0.63), or with the number of pediatric LTs performed per year and center (P = 0.92). Internationally, there is a wide variety in anticoagulation and antiplatelet strategies after pediatric LT. Efforts must be made to design a prospective multicentric trial to identify the optimal antithrombotic strategy.

Perioperative Complications in Neonatal Surgery: Biliary Atresia and Choledochal Malformations.

Biliary atresia (BA) and congenital choledochal malformations (CCM) are rare. Both pathologies must (BA) or may (CCM) be operated during the neonatal period or early infancy. We briefly describe the classical operative techniques for both pathologies, followed by the most common and severe perioperative complications encountered during and up to 30 days after surgery in children operated for BA and CCM early in life. For patients with BA, intestinal complications represent the most common and hazardous perioperative surgical complications. Cholangitis is the most frequently encountered medical complication post hepato-porto-enterostomy. For CCM, it seems that neonates encounter little perioperative complications; however, reports are scarce; bile leak and/or cholangitis are the most reported. Overall, for patients with CCM, the literature is ambivalent whether more perioperative complications occur in the younger or in the older patient, and whether these occur more frequently in those symptomatic or asymptomatic at operation. It is difficult to give clear advice for when children with asymptomatic CCM should be operated, and benefits and risks must be carefully counterbalanced. Perioperative mortality for both BA and CCM is low and is reported to be around 1 to 2%.