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Management of children with acute liver failure is challenging. In this retrospective study, paediatric patients diagnosed with ALF at our centre, in the last 26 years, were divided into two groups (G1 = diagnosed from 1997 to 2009; G2 = from 2010 to 2022) and compared to see whether they differed with regard to aetiologies, need for liver transplantation (LT), and outcome. A total of 90 children (median age 4.6 years, range 1.2-10.4; M/F = 43/47) were diagnosed with ALF, by autoimmune hepatitis (AIH) in 16 (18%), paracetamol overdose in 10 (11%), Wilson disease in 8 (9%), and other causes in 19 (21%); 37 (41%) had indeterminate ALF (ID-ALF). Comparing the two periods, the clinical features, aetiologies, and median peak values of INR [3.8 (2.9-4.8) in G1 vs. 3.2 (2.4-4.8) in G2] were similar ( p > 0.05). The percentage of ID-ALF tended to be higher in G1 compared to G2 (50% vs. 32% in G2, p = 0.09). The overall percentage of patients diagnosed with Wilson disease, inborn errors of metabolism, neonatal hemochromatosis or viral infection was higher in G2 (34% vs. 13% in G1, p = 0.02). A total of 21/90 patients (23%; 5 with indeterminate ALF) were treated with steroids; 12 (14%) required extracorporeal liver support treatment. The need for LT was significantly higher in G1 compared to G2 (56% vs. 34%; p = 0.032). Among 37 children with ID-ALF, 6 (16%) developed aplastic anaemia (all in G2, p < 0.001). The survival rate at last follow up was of 94%. On a KM curve, the transplant-free survival was lower in G1 compared to G2. In conclusion, we report a lower need for LT in children diagnosed with PALF during the most recent period compared to the first era. This suggests improvements over time in the diagnosis and management of children with PALF.

Background: The current gold standard to diagnose T-cell-mediated acute rejection (TCMR) requires liver histology. Using data from the ChilSFree study on immune response after paediatric liver transplantation (pLT), we aimed to assess whether soluble cytokines can serve as an alternative diagnostic tool in children suspected to have TCMR., Methods: A total of n = 53 blood samples obtained on the day of or up to 3 days before liver biopsy performed for suspected TCMR at median 18 days (range 7-427) after pLT in n = 50 children (38% female, age at pLT 1.8 (0.5-17.5) years) were analysed for circulating cytokine levels using Luminex-based Multiplex technology. Diagnostic accuracy of cytokine concentrations was assessed using a multivariable model based on elastic net regression and gradient boosting machine analysis., Results: TCMR was present in 68% of biopsies. There was strong evidence that patients with TCMR had increased levels of soluble CXCL8, CXCL9, CXCL10, IL-16, IL-18, HGF, CCL4, MIF, SCGF-β, and HGF before biopsy. There was some evidence for increased levels of sCD25, ICAM-1, IL-6, IL-3, and CCL11. Diagnostic value of both single cytokine levels and a combination of cytokines and clinical markers was poor, with AUROCs not exceeding 0.7., Conclusion: Patients with TCMR showed raised levels of cytokines and chemokines reflective of T-cell activation and chemotaxis. Despite giving insight into the mechanisms of TCMR, the diagnostic value of soluble cytokines for the confirmation of TCMR in a clinical scenario of suspected TCMR is poor.

(1) Background: Post-transplant lymphoproliferative disease (PTLD) is a significant complication of solid organ transplantation (SOT). However, there is lack of consensus in PTLD management. Our aim was to establish a present benchmark for comparison between international centers and between various organ transplant systems and modalities; (2) Methods: A cross-sectional questionnaire of relevant PTLD practices in pediatric transplantation was sent to multidisciplinary teams from 17 European center members of ERN TransplantChild to evaluate the centers' approach strategies for diagnosis and treatment and how current practices impact a cross-sectional series of PTLD cases; (3) Results: A total of 34 SOT programs from 13 European centers participated. The decision to start preemptive treatment and its guidance was based on both EBV viremia monitoring plus additional laboratory methods and clinical assessment (61%). Among treatment modalities the most common initial practice at diagnosis was to reduce the immunosuppression (61%). A total of 126 PTLD cases were reported during the period 2012-2016. According to their histopathological classification, monomorphic lesions were the most frequent (46%). Graft rejection after PTLD remission was 33%. Of the total cases diagnosed with PTLD, 88% survived; (4) Conclusions: There is still no consensus on prevention and treatment of PTLD, which implies the need to generate evidence. This might successively allow the development of clinical guidelines.

Italy was one of the first industrialized countries to implement a program of routine vaccination against hepatitis B virus (HBV) infection. However, currently, no HBV vaccine is administered at birth if the screened mother is HBsAg negative, whilst babies born to HBsAg positive mothers are given vaccine and hepatitis B immunoglobulin, within 12-24 post-delivery hours. A single center retrospective analysis of policies and practices to prevent mother-to-child transmission of HBV was carried out, to evaluate their adherence to HBV care guidelines. Paired maternal-infant medical records for consecutive live births, between January 2015 and December 2019, were reviewed at the AOU Città della Salute e Scienza di Torino, where a total of 235/35,506 babies (0.7%) were born to HBsAg positive mothers. Markers of active viral replication, i.e., HBV DNA level and/or HBeAg, were reported in only 66/235 (28%) of the mothers' medical records. All newborns had immunoprophylaxis at birth: 61% at <12 h, 31% between 12 and 24 h, 7% between 24 and 36 h and 1% at >36 h. In 2019, two cases of vertical HBV transmission occurred, despite timely immunoprophylaxis, as their mothers' viral load was detected too late for antiviral prophylaxis. Missed early identification of pregnant women with high viremia levels or late vaccinations may contribute to perinatal HBV infection. Immunoprophylaxis should be given to babies born to HBsAg positive mothers at the latest within 12 h. In Italy, policies aimed at achieving the WHO 2030 goal of eliminating viral hepatitis should be further implemented.

Background. Percutaneous transhepatic cholangiography (PTC) is an established treatment in the management of biliary strictures. The aim of our study was to determine the incidence of PTC-related infectious complications in transplanted children, and identify their precise aetiol-ogy. Methods. We retrospectively reviewed all PTC performed from January 2017 to October 2020 in our center. Before the procedure, all patients received antibiotic prophylaxis defined as first line, while second line was used in case of previously microbiological isolation. Cholangitis was defined as fever (>38.5°) and elevated inflammatory markers after PTC, while sepsis included hemodynamic instability in addition to cholangitis. Results. One hundred and fifty-seven PTCs from 50 pediatric recipients were included. The overall incidence of cholangitis and sepsis after PTC was 44.6% (70/157) and 3.2% (5/157), respectively, with no fatal events. Blood cultures yielded positive results in 15/70 cases (21.4%). Enterococcus faecium and Pseudomonas aeruginosa were the most common isolated pathogens. Multidrug-resistant (MDR) pathogens were found in 11/50 patients (22%). Conclusion. PTC is associated with a relatively high rate of post-procedural cholangitis, although with low rate of sepsis and no fatal events. Blood cultures allowed to find a precise aetiology in roughly a quarter of the cases, showing prevalence of Enterococcus faecium and Pseudomonas aeruginosa .