Faster discharge with lactated ringers than normal saline in first 72 h of acute pancreatitis: A multicenter randomized trial.

Objectives: Data driven strategies for acute pancreatitis (AP) in pediatrics are limited; adult data suggests lactated ringers (LR) compared to normal saline (NS) resulted in favorable outcomes, but has not been studied in pediatrics. Our objective was to evaluate the efficacy of LR during the first 48 h of an AP episode compared with NS.

Study Design: A multisite randomized controlled clinical trial, from 2015 to 2020 (Clinical Trials.

An online course introducing medical students to research.

Introduction: Research is an important aspect of many medical students' training. However, many medical students are not required to complete a scholarly project, and formal research training is often fragmented across the medical school curriculum. Thus, we developed an online, structured, asynchronous set of modules to introduce trainees to multiple topics relevant to the conduct of research.

Serum biomarkers correlated with liver stiffness assessed in a multicenter study of pediatric cholestatic liver disease.

Background And Aims: Detailed investigation of the biological pathways leading to hepatic fibrosis and identification of liver fibrosis biomarkers may facilitate early interventions for pediatric cholestasis.

Approach And Results: A targeted enzyme-linked immunosorbent assay-based panel of nine biomarkers (lysyl oxidase, tissue inhibitor matrix metalloproteinase (MMP) 1, connective tissue growth factor [CTGF], IL-8, endoglin, periostin, Mac-2-binding protein, MMP-3, and MMP-7) was examined in children with biliary atresia (BA; n = 187), alpha-1 antitrypsin deficiency (A1AT; n = 78), and Alagille syndrome (ALGS; n = 65) and correlated with liver stiffness (LSM) and biochemical measures of liver disease. Median age and LSM were 9 years and 9.

Fat Soluble Vitamin Assessment and Supplementation in Cholestasis.

Malnutrition in children with chronic cholestasis is a prevalent issue and a major risk factor for adverse outcomes. Fat soluble vitamin (FSV) deficiency is an integral feature of cholestatic disease in children, often occurring within the first months of life in those with neonatal cholestasis and malnutrition. This review focuses on FSVs in cholestasis, with particular emphasis on a practical approach to surveillance and supplementation that includes approaches that account for differing local resources.

Neurodevelopmental Outcomes in Children With Inherited Liver Disease and Native Liver.

Objective: To evaluate neurodevelopmental status among children with inherited cholestatic liver diseases with native liver and variables predictive of impairment.

Methods: Participants with Alagille syndrome (ALGS), progressive familial intrahepatic cholestasis (PFIC), and alpha 1 antitrypsin deficiency (A1AT) enrolled in a longitudinal, multicenter study and completed the Wechsler Preschool and Primary Scale of Intelligence-III or Intelligence Scale for Children-IV. Full Scale Intelligence Quotient (FSIQ) was analyzed continuously and categorically (>100, 85-99, 70-84, <70).

Genetic spectrum and clinical characteristics of 3β-hydroxy-Δ-C-steroid oxidoreductase (HSD3B7) deficiency in China.

Background: Biallelic variants in HSD3B7 cause 3β-hydroxy-Δ-C-steroid oxidoreductase (HSD3B7) deficiency, a life-threatening but treatable liver disease. The goal of this study was to obtain detailed information on the correlation between the genotype and phenotype of HSD3B7 deficiency and to report on responses to primary bile acid therapy.

Methods: The medical records of a cohort of 39 unrelated patients with genetically and biochemically confirmed HSD3B7 deficiency were examined to determine whether there exist genotype-phenotype relationships in this bile acid synthesis disorder.

Cholbam® and Zellweger spectrum disorders: treatment implementation and management.

Background: Zellweger spectrum disorders (ZSDs) are a rare, heterogenous group of autosomal recessively inherited disorders characterized by reduced peroxisomes numbers, impaired peroxisomal formation, and/or defective peroxisomal functioning. In the absence of functional peroxisomes, bile acid synthesis is disrupted, and multisystem disease ensues with abnormalities in the brain, liver, kidneys, muscle, eyes, ears, and nervous system.

Main Body: Liver disease may play an important role in morbidity and mortality, with hepatic fibrosis that can develop as early as the postnatal period and often progressing to cirrhosis within the first year of life.

Mutation Analysis and Disease Features at Presentation in a Multi-Center Cohort of Children With Monogenic Cholestasis.

Objectives: To advance our understanding of monogenic forms of intrahepatic cholestasis.

Methods: Analyses included participants with pathogenic biallelic mutations in adenosine triphosphate (ATP)-binding cassette subfamily B member 11 (ABCB11) (bile salt export pump; BSEP) or adenosine triphosphatase (ATPase) phospholipid transporting 8B1 (ATP8B1) (familial intrahepatic cholestasis; FIC1), or those with monoallelic or biallelic mutations in adenosine triphosphate (ATP)-binding cassette subfamily B member 4 (ABCB4) (multidrug resistance; MDR3), prospectively enrolled in the Longitudinal Study of Genetic Causes of Intrahepatic Cholestasis (LOGIC; NCT00571272) between November 2007 and December 2013. Summary statistics were calculated to describe baseline demographics, history, anthropometrics, laboratory values, and mutation data.

Use of a Comprehensive 66-Gene Cholestasis Sequencing Panel in 2171 Cholestatic Infants, Children, and Young Adults.

Objectives: Cholestasis is caused by a wide variety of etiologies, often genetic in origin. Broad overlap in clinical presentations, particularly in newborns, renders prioritizing diagnostic investigations challenging. In this setting, a timely, comprehensive assessment using a multigene panel by a clinical diagnostic laboratory would likely prove useful.

Outcomes of Childhood Cholestasis in Alagille Syndrome: Results of a Multicenter Observational Study.

Alagille syndrome (ALGS) is an autosomal dominant multisystem disorder with cholestasis as a defining clinical feature. We sought to characterize hepatic outcomes in a molecularly defined cohort of children with ALGS-related cholestasis. Two hundred and ninety-three participants with ALGS with native liver were enrolled.

Longitudinal Outcomes in Young Patients with Alpha-1-Antitrypsin Deficiency with Native Liver Reveal that Neonatal Cholestasis is a Poor Predictor of Future Portal Hypertension.

Objectives: To identify predictors of portal hypertension, liver transplantation, and death in North American youth with alpha-1-antitrypsin (AAT) deficiency, and compare with patients with AAT deficiency elsewhere.

Study Design: The Childhood Liver Disease Research Network Longitudinal Observational Study of Genetic Causes of Intrahepatic Cholestasis is a prospective, cohort study of pediatric cholestatic liver diseases, including AAT deficiency, enrolling PIZZ and PISZ subjects 0-25 years of age seen since November 2007 at 17 tertiary care centers in the US and Canada. Data from standard-of-care baseline and annual follow-up visits were recorded from medical records, history, physical examination, and laboratory studies.

Implementing a Process to Systematically Identify and Address Poor Medication Adherence in Pediatric Liver Transplant Recipients.

Objectives: Poor adherence to medication following pediatric liver transplantation remains a major challenge, with some estimates suggesting that 50% of adolescent liver transplant recipients exhibit reduced medication adherence. To date, no gold standard has emerged to address this challenge; however, system interventions are most likely to be successful. We sought to implement a system to identify and address adherence barriers in a liver transplant clinic.

Who's at Risk? A Prognostic Model for Severity Prediction in Pediatric Acute Pancreatitis.

Objectives: The aim of the study was to validate and optimize a severity prediction model for acute pancreatitis (AP) and to examine blood urea nitrogen (BUN) level changes from admission as a severity predictor.

Study Design: Patients from 2 hospitals were included for the validation model (Children's Hospital of the King's Daughters and Children's National Hospital). Children's Hospital of the King's Daughters and Cincinnati Children's Hospital Medical Center data were used for analysis of BUN at 24 to 48 hours.

Open-label Phase 3 Continuation Study of Cholic Acid in Patients With Inborn Errors of Bile Acid Synthesis.

Background: In patients with bile acid synthesis disorders (BASD), impairment in the primary bile acid synthetic pathway leads to reduced primary bile acids, upregulated synthesis of cholesterol, and production and accumulation of hepatotoxic atypical bile acids. Primary bile acid therapy downregulates bile acid synthesis, reduces the production of hepatotoxic intermediates, and produces a functional bile acid pool fostering normal liver function.

Methods: This phase 3, open-label, single-arm study included patients with BASD who had received cholic acid (10-15 mg · kg · day) as part of a previous study, or were newly diagnosed.

Bile Acid Synthesis Disorder Masquerading as Intractable Vitamin D-Deficiency Rickets.

Vitamin D-deficiency rickets, not responding to large treatment doses of oral vitamin D, suggest rare receptor mutations, malabsorption, or hepatobiliary dysfunction. We present a set of twins of Hispanic origin who presented with refractory vitamin D-deficiency rickets and failure to thrive (FTT) at 6 months of age. On follow-up, mild elevations in serum alanine transaminases and normal aspartate aminotransferase were noted.

Long-Term Cholic Acid Treatment in a Patient with Zellweger Spectrum Disorder.

Zellweger spectrum disorders (ZSDs) are a subgroup of peroxisomal biogenesis disorders with a generalized defect in peroxisome function. Liver disease in ZSDs has been associated with the lack of peroxisomal β-oxidation of C-bile acid intermediates to form primary C-bile acids, which prevents normal physiologic feedback and leads to accumulation of hepatotoxic bile acid intermediates. Primary bile acid therapy, oral cholic acid (CA), as adjunctive treatment for ZSDs, restores physiologic feedback inhibition on bile acid synthesis and inhibits formation of hepatotoxic bile acid intermediates.

Opportunities for life course research through the integration of data across Clinical and Translational Research Institutes.

Introduction: Early life exposures affect health and disease across the life course and potentially across multiple generations. The Clinical and Translational Research Institutes (CTSIs) offer an opportunity to utilize and link existing databases to conduct lifespan research.

Methods: A survey with Lifespan Domain Taskforce expert input was created and distributed to lead lifespan researchers at each of the 64 CTSIs.

Inborn Errors of Bile Acid Metabolism.

Inborn errors of bile acid metabolism are rare causes of neonatal cholestasis and liver disease in older children and adults. The diagnosis should be considered in the context of hyperbilirubinemia with normal serum bile acids and made by urinary liquid secondary ionization mass spectrometry or DNA testing. Cholic acid is an effective treatment of most single-enzyme defects and patients with Zellweger spectrum disorder with liver disease.

Bone Density in Children With Chronic Liver Disease Correlates With Growth and Cholestasis.

Osteopenia and bone fractures are significant causes of morbidity in children with cholestatic liver disease. Dual-energy X-ray absorptiometry (DXA) analysis was performed in children with intrahepatic cholestatic diseases who were enrolled in the Longitudinal Study of Genetic Causes of Intrahepatic Cholestasis in the Childhood Liver Disease Research Network. DXA was performed on participants aged >5 years (with native liver) diagnosed with bile acid synthetic disorder (BASD), alpha-1 antitrypsin deficiency (A1AT), chronic intrahepatic cholestasis (CIC), and Alagille syndrome (ALGS).

Long-Term Cholic Acid Therapy in Zellweger Spectrum Disorders.

Zellweger spectrum disorders (ZSDs), a subgroup of peroxisomal biogenesis disorders, have a generalized defect in peroxisome function. Liver disease in ZSDs has been linked to accumulation of C-bile acid intermediates due to the lack of peroxisomal β-oxidation of these intermediates to form primary C-bile acids. Oral treatment with primary bile acid, cholic acid (CA), inhibits formation of hepatotoxic C-bile acids by restoring normal physiologic feedback inhibition on bile acid synthesis.

Serum Unconjugated Bile Acids and Small Bowel Bacterial Overgrowth in Pediatric Intestinal Failure: A Pilot Study.

Background: We determined qualitative and quantitative serum unconjugated bile acid (SUBA) levels among children with history of intestinal failure (IF) and suspected small bowel bacterial overgrowth (SBBO).

Methods: This was a single-center, case-control pilot study conducted at Cincinnati Children's Hospital Medical Center. Children with history of IF and suspected SBBO were enrolled as subjects.

Chapter 9. Words From Partner Societies.

On the occasion of the 50th anniversary of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), its close partner associations submitted comments and felicitations which are presented here. These include words from the Latin American (LASPGHAN), North American (NASPGHAN) and Panarabian Societies (PASPGHAN) and the Commonwealth Association (CAPGHAN) of Paediatric Gastroenterology, Hepatology and Nutrition, the Federation of International Societies of Paediatric Gastroenterology, Hepatology and Nutrition (FISPGHAN), the European Academy of Pediatrics (EAP), the European Pediatric Association/Union of National Pediatric Societies (EPA-UNEPSA), the International Pediatric Association (IPA), the European Crohn's and Colitis Organisation (ECCO), European Society for Clinical Nutrition and Metabolism (ESPEN) , the Federation of European Nutrition Societies (FENS), and United European Gastroenterology (UEG).

Pancreatic Enzyme Replacement Therapy Use in Infants With Cystic Fibrosis Diagnosed by Newborn Screening.

Objectives: The aim of the study is to describe pancreatic enzyme practices during the first year of life in infants with cystic fibrosis (CF) and evaluate associations between dosing and outcomes, including growth and gastrointestinal (GI) symptoms.

Methods: We analyzed data from a subset of infants who were in a prospective cohort study conducted at 28 US CF centers. Anthropometric measurements and medications were recorded at each visit.

Bile Acid Synthesis Disorders in Arabs: A 10-year Screening Study.

Objectives: Early diagnosis of bile acid synthesis disorders (BASDs) is important because, untreated, these conditions can be fatal. Our objectives were to screen children with cholestasis or unexplained liver disease for BASD and in those with confirmed BASD to evaluate the effectiveness of cholic acid therapy.

Methods: A routine serum total bile acid measurement was performed on children with cholestasis, liver cirrhosis, and liver failure.