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Background and aims: Alagille syndrome (ALGS) is a multisystem disorder, characterized by cholestasis. Existing outcome data are largely derived from tertiary centers, and real-world data are lacking. This study aimed to elucidate the natural history of liver disease in a contemporary, international cohort of children with ALGS. Approach and results: This was a multicenter retrospective study of children with a clinically and/or genetically confirmed ALGS diagnosis, born between January 1997 and August 2019. Native liver survival (NLS) and event-free survival rates were assessed. Cox models were constructed to identify early biochemical predictors of clinically evident portal hypertension (CEPH) and NLS. In total, 1433 children (57% male) from 67 centers in 29 countries were included. The 10 and 18-year NLS rates were 54.4% and 40.3%. By 10 and 18 years, 51.5% and 66.0% of children with ALGS experienced >= 1 adverse liver-related event (CEPH, transplant, or death). Children (>6 and = 5.0 and = 10.0 mg/dl had an 8.0-fold (95% CI, 3.4-18.4) increased risk of developing CEPH compared with those 10.0 mg/dl were associated with a 4.8 (95% CI, 2.4-9.7) and 15.6 (95% CI, 8.7-28.2) increased risk of transplantation relative to = 5.0 mg/dl, with 79% reaching adulthood with native liver (p < 0.001). Conclusions: in this large international cohort of ALGS, only 40.3% of children reach adulthood with their native liver. A TB, This study received funding support from the following agencies: The Alagille Syndrome Alliance, Mirum Pharmaceuticals Inc. and Albireo Pharma, Inc. who provided unrestricted educational grants to the Hospital for Sick Children (SickKids Foundation). The study sponsors were not involved in the conduct of the research study or preparation of the manuscript.

The incidence of choledocolithiasis is reported to be increasing in children. As for the adult population, several different therapeutic strategies have been described, however it is unclear which of those should be considered the gold standard. There is evidence-based literature in adults that supports a combined "rendez-vous" endoscopic retrograde cholangiopancreatography-laparoscopic cholecystectomy technique. This allows management of the choledocholithiasis during the same anesthetic episode as the cholecystectomy. By contrast, there are just two case reports in children reporting this approach. The aim of this study is to report our experience with this technique in a series of children with choledocholithiasis.All patients who underwent the "rendez-vous technique" at our institution between 2009 and 2020 were reviewed and evaluated for outcomes and complications.Eleven children with cholecysto-choledocholithiasis were evaluated: the procedure was successful in 10 whereas in one patient it was aborted due to technical difficulties. All patients resolved their clinical condition without major complications.To our knowledge, this is the first consistent series of "rendez-vous technique" in the pediatric population, proving its feasibility and safety.

OBJECTIVES: Sofosbuvir/Ledipasvir (SOF/LDV) has been approved by the European Medicine Agency (EMA) for the treatment of children and adolescents (at least 3 years of age) with chronic hepatitis C (CHC) genotype 1, 3, and 4 infection. The aim of this study was to evaluate the efficacy and safety of SOF/LDV in adolescents (12 to

BACKGROUND Hematopoietic stem cell transplantation (HSCT) is curative in patients with primary immunodeficiencies. However, pre-HSCT conditioning entails unacceptably high risks if the liver is compromised. The presence of a recurrent opportunistic infection affecting the biliary tree and determining liver cirrhosis with portal hypertension posed particular decisional difficulties in a 7-year-old child with X-linked CD40-ligand deficiency. We aim at adding to the scanty experience available on such rare cases, as successful management with sequential liver transplantation (LT) and HSCT has been reported in detail only in 1 young adult to date. METHODS A closely sequential strategy, with a surgical complication-free LT, followed by reduced-intensity conditioning, allowed HSCT to be performed only one month after LT, preventing Cryptosporidium parvum recolonization of the liver graft. RESULTS Combined sequential LT and HSCT resolved the cirrhotic evolution and corrected the immunodeficiency so that the infection responsible for the progressive sclerosing cholangitis did not recur. CONCLUSIONS Hopefully, this report of the successful resolution of a potentially fatal combination of immunodeficiency and chronic opportunistic infection with end-stage organ damage in a child will encourage others to adapt a sequential transplant approach to this highly complex pathology. However, caution is to be exercised to carefully balance the risks intrinsic to transplant surgery and immunosuppression in primary immunodeficiencies.

To obtain optimal visualization of the colonic mucosa during gastrointestinal endoscopic procedures, an adequate bowel preparation is mandatory, but a standardized protocol is still lacking for pediatric patients. Polyethylene glycol (PEG) is currently the most used laxative, but the amount of liquid to be taken orally is a large volume for the pediatric population and it may not be well tolerated. The aim of our preliminary trial was to evaluate efficacy, tolerability, and safety of sodium picosulphate-magnesium citrate (SPMC) used as bowel preparation before colonoscopy in children. Fifty children who needed a colonoscopy were prospectively enrolled between April and December 2013 and SPMC was administered to them as bowel preparation. A questionnaire about the product tolerance was completed by the patients' parents. The grade of bowel preparation and any related side effect were evaluated. The mean value of the Boston Bowel Preparation Scale was 7, out of a maximum of 9. Only 5 patients had an inadequate bowel preparation. Seventy percent of the patients considered the taste of the preparation very palatable. The remaining 26% considered it not palatable or not palatable at all. During the preparation, 18% of children complained of nausea, 20% abdominal pain, 2% vomiting, and 2% manifested headache. Bowel preparation with SPMC offers an efficient alternative to PEG and allows, on equal terms of efficacy, tolerability and safety, a much lower amount of laxative to ingest, and remarkable quality, especially in infants and toddlers.

In February 2020, the COVID-19 pandemic overwhelmed Italy. We retrospectively reviewed all attendances and emergency (A&E) admissions due to foreign-body ingestions (FBIs) to an Italian pediatric referral hospital, from February 24 to April 24, 2020, COVID-19 lockdown and compared them with the same period in the previous 4 years. A total of 101 cases were recorded. Mean age of admission was 4.6 years. Groups did not differ for gender (P = 0.4) or age (P = 0.3). Among FBIs ingestions, 24.0% occurred in children with

The detection of antimitochondrial antibodies (AMAs) is an important criterion for the diagnosis of primary biliary cirrhosis (PBC). During the last decade, the mitochondrial autoantigens have been cloned, sequenced, and identified as members of the 2-oxo-acid dehydrogenase pathway, including the E2 subunits of pyruvate dehydrogenase (PDC-E2), branched-chain 2-oxo-acid dehydrogenase (BCOADC-E2), and 2-oxo-glutarate dehydrogenase (OGDC-E2). We have developed a rapid and sensitive diagnostic test for use in PBC based on a triple hybrid recombinant molecule (r-MIT3) that contains the autoepitopes of PDC-E2, BCOADC-E2, and OGDC-E2. To help understand the frequency and antigen specificity of AMAs in an asymptomatic population and to identify patients with early disease, we investigated the prevalence of AMA, by enzyme-linked immunosorbent assay (ELISA), in a cohort of 1,530 people from northern Italy. Positive sera were further analyzed for immunoglobulin (Ig) isotypes, subclasses, and epitopes of AMA by a combination of ELISA and immunoblotting. In this cohort of 1,530 people, 9 (0.5%) reacted to r-MIT3 by ELISA. Of the 9 reactive sera, 2 recognized PDC-E2, 2 of 9 recognized BCOADC-E2, 1 of 9 recognized OGDC-E2, 2 of 9 recognized both PDC-E2 and BCOADC-E2, and 1 of 9 recognized PDC-E2 and OGDC-E2. AMA reactivity was primarily IgM and IgA. Epitope mapping revealed an AMA pattern of reactivity to PDC-E2 that differed from that found in patients with histologically proven PBC in most of the sera. However, 1 sera of a 72-year-old female with a normal alkaline phosphatase had an AMA profile identical to typical PBC. After a variable follow-up period (8-14 months), sera from 8 of 9 of these people were re-obtained for AMA and relative epitope mapping. Interestingly, the reactivity had a wider AMA pattern than before.