Longitudinal response to standard of care in pediatric metabolic dysfunction-associated steatotic liver disease: Rates of improvement and worsening, and factors associated with outcomes.

Background Aims: Longitudinal outcomes in children with metabolic dysfunction-associated steatotic liver disease (MASLD) remain unclear due to the absence of a standardized monitoring approach. This study aimed to 1) define improvement and worsening in children with MASLD, 2) estimate rates of improvement or deterioration with standard of care (SOC) over one and two years, and 3) identify baseline and longitudinal factors associated with improvement or worsening.

Approach And Results: Using data from two large randomized controlled trials, we derived definitions for composite improvement and worsening of MASLD based on associations between changes in ALT, GGT, and liver histology after one and two years.

Systematic review of exercise for the treatment of pediatric metabolic dysfunction-associated steatotic liver disease.

Background & Aims: Steatotic liver disease affects approximately 1 in 10 children in the U.S. and increases the risk of cirrhosis, diabetes, and cardiovascular disease.

Patient perspective on exercise practices, preferences, and barriers in pediatric nonalcoholic fatty liver disease: A multicenter survey.

Background/aims: Nonalcoholic fatty liver disease (NAFLD) is prevalent among children, and lifestyle modification is the primary treatment approach. However, the optimal exercise duration, frequency, and intensity for managing NAFLD remain undefined. This study aimed to gain insights from the patient perspective by examining exercise behaviors, preferences, and barriers in children with NAFLD.

Pentadecanoic Acid Supplementation in Young Adults with Overweight and Obesity: A Randomized Controlled Trial.

Background: Obesity and its associated comorbidities are major public health concerns for which nutrition is central to disease prevention and management. Pentadecanoic acid (C15:0) has the potential for beneficial effects on obesity, but supplementation has not been studied in humans.

Objectives: The primary objective was to investigate changes in plasma C15:0 levels after daily supplementation for 12 wk.

Development of Fibro-PeN, a clinical prediction model for moderate-to-severe fibrosis in children with nonalcoholic fatty liver disease.

Background And Aims: Liver fibrosis is common in children with NAFLD and is an important determinant of outcomes. High-performing noninvasive models to assess fibrosis in children are needed. The objectives of this study were to evaluate the performance of existing pediatric and adult fibrosis prediction models and to develop a clinical prediction rule for identifying moderate-to-severe fibrosis in children with NAFLD.

Prevalence of Elevated ALT in Adolescents in the US 2011-2018.

Objective: The objective of this study is to characterize suspected nonalcoholic fatty liver disease (NAFLD) using elevated alanine aminotransferase (ALT) in a diverse and nationally representative cohort of adolescents and to characterize higher ALT elevation in adolescents with obesity.

Methods: Data from the National Health and Nutrition Examination Survey 2011-2018 were analyzed for adolescents 12-19 years. Participants with causes for elevated ALT other than NAFLD were excluded.

Incidence of Type 2 Diabetes in Children With Nonalcoholic Fatty Liver Disease.

Background & Aims: Type 2 diabetes (T2D) is a growing problem in children. Children with NAFLD are at potentially high risk for developing T2D; however, the incidence of T2D in this population is unknown. This study aimed to determine the incidence of T2D in children with NAFLD and identify associated risk factors.

Nonalcoholic fatty liver disease risk and histologic severity are associated with genetic polymorphisms in children.

Background And Aims: NAFLD is the most common chronic liver disease in children. Large pediatric studies identifying single nucleotide polymorphisms (SNPs) associated with risk and histologic severity of NAFLD are limited. Study aims included investigating SNPs associated with risk for NAFLD using family trios and association of candidate alleles with histologic severity.

A unique pancreatic phenotype in a child with a WDR19-related ciliopathy: A case report and literature review of pancreatic involvement in ciliopathies.

Ciliopathies are a group of genetic disorders caused by ciliary dysfunction. Thirty-five distinct multi-organ phenotypes have been recognized, with 187 genes associated. We performed a literature review of pancreatic involvement in ciliopathies and found that pancreatic disease is an uncommon phenotype described in only a handful of these genetic disorders.

Dietary sugar restriction reduces hepatic de novo lipogenesis in adolescent boys with fatty liver disease.

BACKGROUNDHepatic de novo lipogenesis (DNL) is elevated in nonalcoholic fatty liver disease (NAFLD). Improvements in hepatic fat by dietary sugar reduction may be mediated by reduced DNL, but data are limited, especially in children. We examined the effects of 8 weeks of dietary sugar restriction on hepatic DNL in adolescents with NAFLD and correlations between DNL and other metabolic outcomes.

Dairy Fat Intake, Plasma Pentadecanoic Acid, and Plasma Iso-heptadecanoic Acid Are Inversely Associated With Liver Fat in Children.

Objectives: We sought to evaluate the relevance of pediatric dairy fat recommendations for children at risk for nonalcoholic fatty liver disease (NAFLD) by studying the association between dairy fat intake and the amount of liver fat. The effects of dairy fat may be mediated by odd chain fatty acids (OCFA), such as pentadecanoic acid (C15:0), and monomethyl branched chain fatty acids (BCFA), such as iso-heptadecanoic acid (iso-C17:0). Therefore, we also evaluated the association between plasma levels of OCFA and BCFA with the amount of liver fat.

Incidence of Depression and Anxiety in a Cohort of Adolescents With Nonalcoholic Fatty Liver Disease.

Objectives: To determine the incidence of clinically diagnosed depression and anxiety in adolescents with nonalcoholic fatty liver disease (NAFLD).

Methods: This was a prospective, longitudinal cohort study between January 1, 2012 and July 1, 2018 conducted in a Children's Hospital Pediatric Gastroenterology Clinic. Participants included adolescents 12 to 17 years old at baseline with biopsy-confirmed NAFLD.

Incidence of Nonalcoholic Fatty Liver Disease in Children: 2009-2018.

Background And Objectives: In 2007, the American Academy of Pediatrics recommended that children with obesity should be screened for nonalcoholic fatty liver disease (NAFLD). Population epidemiology reveals that NAFLD is common in children; however, little is known about rates of clinical diagnosis. In this study, we aim to determine screening practices, annual incidence, and clinical characteristics of NAFLD in children within an integrated community health system.

Alanine Aminotransferase and Gamma-Glutamyl Transpeptidase Predict Histologic Improvement in Pediatric Nonalcoholic Steatohepatitis.

Background And Aims: Predictive, noninvasive tools are needed to monitor key features of nonalcoholic fatty liver disease (NAFLD) in children that relate to improvement in liver histology. The purpose of this study was to evaluate the relationship between liver chemistries and liver histology using data from the CyNCh (Cysteamine Bitartrate Delayed-Release for the Treatment of NAFLD in Children) clinical trial.

Approach And Results: This study included 146 children.

Evaluation of Quantitative Imaging Biomarkers for Early-phase Clinical Trials of Steatohepatitis in Adolescents.

Objectives: Early-phase pediatric nonalcoholic fatty liver disease (NAFLD) clinical trials are designed with noninvasive parameters to assess potential efficacy. Increasingly, these parameters include magnetic resonance imaging (MRI)-derived proton density fat fraction (PDFF) and MR elastography (MRE)-derived shear stiffness as biomarkers of hepatic steatosis and fibrosis, respectively. Understanding fluctuations in these measures is essential for calculating trial sample sizes, interpreting results, and planning clinical drug trials in children with NAFLD.

Normal range for MR elastography measured liver stiffness in children without liver disease.

Background: Magnetic resonance elastography (MRE) can determine the presence and stage of liver fibrosis. Data on normative MRE values, while reported in adults, are limited in children.

Purpose: To determine the distribution of MRE-measured liver stiffness in children without liver disease.

Microbiome Signatures Associated With Steatohepatitis and Moderate to Severe Fibrosis in Children With Nonalcoholic Fatty Liver Disease.

Background & Aims: The intestinal microbiome might affect the development and severity of nonalcoholic fatty liver disease (NAFLD). We analyzed microbiomes of children with and without NAFLD.

Methods: We performed a prospective, observational, cross-sectional study of 87 children (age range, 8-17 years) with biopsy-proven NAFLD and 37 children with obesity without NAFLD (controls).

Effect of a Low Free Sugar Diet vs Usual Diet on Nonalcoholic Fatty Liver Disease in Adolescent Boys: A Randomized Clinical Trial.

Importance: Pediatric guidelines for the management of nonalcoholic fatty liver disease (NAFLD) recommend a healthy diet as treatment. Reduction of sugary foods and beverages is a plausible but unproven treatment.

Objective: To determine the effects of a diet low in free sugars (those sugars added to foods and beverages and occurring naturally in fruit juices) in adolescent boys with NAFLD.

Clinical Practice Approach to Nonalcoholic Fatty Liver Disease by Pediatric Gastroenterologists in the United States.

Objectives: Nonalcoholic fatty liver disease (NAFLD) is common; however, no information is available on how pediatric gastroenterologists in the United States manage NAFLD. Therefore, study objectives were to understand how pediatric gastroenterologists in the US approach the management of NAFLD, and to identify barriers to care for children with NAFLD.

Methods: We performed structured one-on-one interviews to ascertain each individual pediatric gastroenterologist's approach to the management of NAFLD in children.

A Bibliometric Analysis of Clinical and Translational Research in Pediatric Gastroenterology From 1970 to 2017.

Objectives: Pediatric gastroenterology is a clinical and research discipline principally developed over the past 50 years. Bibliometric methods provide quantitative analysis and identify research trends. Study aims were to characterize the growth and trends in pediatric gastroenterology clinical and translational research using citation analysis.

Clinically Actionable Hypercholesterolemia and Hypertriglyceridemia in Children with Nonalcoholic Fatty Liver Disease.

Objective: To determine the percentage of children with nonalcoholic fatty liver disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or triglycerides was indicated based on National Heart, Lung, and Blood Institute guidelines.

Study Design: This multicenter, longitudinal cohort study included children with NAFLD enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. Fasting lipid profiles were obtained at diagnosis.

Successful Outcome and Biliary Drainage in an Infant with Concurrent Alpha-1-Antitrypsin Deficiency and Biliary Atresia.

We describe the rare instance of concomitant biliary atresia and alpha-1-antitrypsin deficiency and the first documented successful portoenterostomy in this scenario. The potential for dual pathology must be recognized and underscores that prompt diagnosis of biliary atresia, despite concomitant alpha-1-antitrypsin deficiency, is essential to afford potential longstanding native liver function.