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.

Longitudinal evaluation of pediatric and young adult metabolic dysfunction-associated steatotic liver disease defined by MR elastography.

Objectives: To inform clinical monitoring of children and young adults with metabolic dysfunction-associated steatotic liver disease (MASLD) by characterizing the real-world natural history of MASLD and identifying baseline predictors of liver disease progression.

Materials And Methods: This retrospective study included consecutive patients ages < 23 years with MASLD who underwent serial MR elastography (MRE) and/or MR fat fraction (FF) examinations between 09/2009 and 11/2022. Outcomes of MASLD were defined based on maximum ratio values.

Prevalence of subclinical hypothyroidism and longitudinal thyroid-stimulating hormone changes in youth with metabolic dysfunction-associated steatotic liver disease: An observational study.

Background: Studies on adults have shown an association between overt or subclinical hypothyroidism and metabolic dysfunction-associated steatotic liver disease (MASLD). The goal of this study was to assess the relationship between thyroid-stimulating hormone (TSH) levels and the histological characteristics of MASLD in youth.

Methods: This observational study used prospectively collected liver biopsy and clinical data from youth enrolled in 2 pediatric clinical trials in the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN).

Environmental toxicants modulate disease severity in pediatric metabolic dysfunction-associated steatohepatitis.

Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is common in children. We hypothesized environmental toxins could drive progression to metabolic dysfunction-associated steatohepatitis (MASH), and assayed serum toxins and metabolites in children with histologically characterized MASLD/MASH.

Methods: Environmental chemicals, common in household items, perfluoroalkyl substances (PFAS), polybrominated flame retardants (polybrominated diphenyl ethers [PBDEs]), and metabolic profiles were assayed in children enrolled in the multicenter NASH Clinical Research Network Pediatric Database 2.

Renal impairment is prevalent in pediatric NAFLD/MASLD and associated with disease severity.

Objectives: Renal impairment is prevalent in adults with nonalcoholic fatty liver disease (NAFLD/metabolic dysfunction associated steatotic liver disease [MASLD]) and is associated with increased mortality. Pediatric data are limited. Our objective was to determine the prevalence of hyperfiltration or chronic kidney disease (CKD) in children with NAFLD/MASLD and determine links with liver disease severity.

Presurgery health influences outcomes following vertical sleeve gastrectomy in adolescents.

Objective: Weight loss following vertical sleeve gastrectomy (VSG) in youth can range from 10% to 50%. We examined whether there are differences in demographic or metabolic parameters before VSG in youth who achieve above-average weight loss (AAWL) versus below-average weight loss (BAWL) at 1 year post VSG and if youth with BAWL still achieve metabolic health improvements at 1 year post VSG.

Methods: Demographic, anthropometric, and clinical lab data were collected before VSG and at 1, 3, 6, and 12 months after VSG.

Prognostic factors in resolution of nonalcoholic fatty liver disease post bariatric surgery in adolescents.

Background: The long-term effect of bariatric surgery on adolescent non-alcoholic fatty liver disease is not clear.

Objectives: To evaluate longitudinal change in serum alanine aminotransferase (ALT) levels and to determine the factors independently associated with this change over 2 years after bariatric surgery in adolescents with severe obesity.

Setting: An observational prospective cohort from the Teen-LABS Consortium.

Food Insecurity and Pediatric Nonalcoholic Fatty Liver Disease Severity.

Objective: To determine the association between food insecurity and pediatric nonalcoholic fatty liver disease (NAFLD).

Methods: Cross-sectional study of patients < 21 years of age with histologically confirmed NAFLD. The Household Food Security Survey Module was administered to determine food insecurity status.

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.

Clinical Performance of Transient Elastography With Comparison to Quantitative Magnetic Resonance Imaging, Ultrasound, and Biopsy in Children and Adolescents With Known or Suspected Fatty Liver Disease.

Performance of vibration-controlled transient elastography (VCTE) is inadequately validated in pediatric nonalcoholic fatty liver disease (NAFLD). We aimed to assess the technical performance of VCTE in pediatric NAFLD and define the agreement between VCTE and reference standards of imaging and/or biopsy. This prospective study recruited participants with known or suspected NAFLD who underwent a research VCTE examination (FibroScan Mini 430).

Nonalcoholic Steatohepatitis in Children.

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in children. Although environmental factors are major contributors to early onset, children have both shared and unique genetic risk alleles as compared with adults with NAFLD. Treatment relies on reducing environmental risk factors, but many children have persistent diseases.

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.

Histologic Severity of Nonalcoholic Fatty Liver Disease Associates with Reduced Bone Mineral Density in Children.

Background: Lower whole body bone mineral density (BMD) has been reported in children with nonalcoholic fatty liver disease (NAFLD), but potential mediators remain uncertain.

Aims: To assess BMD at multiple skeletal sites in children with confirmed NAFLD and controls with obesity, adjusting for known determinants of BMD, and examine potential mediators.

Methods: We assessed age-, sex-, and race-specific, and height-adjusted BMD z-scores of whole body, lumbar spine, hip, femoral neck and forearm by dual-energy-x-ray absorptiometry in 79 children, 8-19 years old: 46 with biopsy-confirmed NAFLD [29 steatohepatitis (NASH)/17 fatty liver (NAFL)] and 33 controls without liver disease.

Comparison of Quantitative Liver US and MRI in Patients with Liver Disease.

Background Quantitative US techniques can be used to identify changes of liver disease, but data regarding their diagnostic performance and relationship to MRI measures are sparse. Purpose To define associations between quantitative US and MRI measures of the liver in children, adolescents, and young adults with liver disease and to define the predictive ability of quantitative US measures to detect abnormal liver stiffening and steatosis defined with MRI. Materials and Methods In this prospective study, consecutive patients aged 8-21 years and known to have or suspected of having liver disease and body mass index less than 35 kg/m underwent 1.

Exposure to per- and Polyfluoroalkyl Substances and Markers of Liver Injury: A Systematic Review and Meta-Analysis.

Background: Experimental evidence indicates that exposure to certain pollutants is associated with liver damage. Per- and polyfluoroalkyl substances (PFAS) are persistent synthetic chemicals widely used in industry and consumer products and bioaccumulate in food webs and human tissues, such as the liver.

Objective: The objective of this study was to conduct a systematic review of the literature and meta-analysis evaluating PFAS exposure and evidence of liver injury from rodent and epidemiological studies.

Insight Into the Adolescent Patient Experience With Nonalcoholic Fatty Liver Disease.

Objectives: Nonalcoholic fatty liver disease (NAFLD) is the leading chronic liver disease in youth, yet little is known about the adolescent patient's experience with NAFLD, which is key for treatment engagement. We examined adolescents' experiences with NAFLD diagnosis, thoughts on how NAFLD affects their daily life, understanding and perceptions of diagnosis and treatment, and impressions of how to improve care.

Methods: Utilizing a mixed-method design, adolescents with NAFLD (N = 16; Mean age = 15.

Variation in Alanine Aminotransferase in Children with Non-Alcoholic Fatty Liver Disease.

Background: Pediatric non-alcoholic fatty liver disease (NAFLD) is a major public health concern. Aminotransferase (ALT) is frequently used for screening and monitoring, but few studies have reported typical patterns of ALT elevation in children. Methods: TARGET-NASH is a real-world longitudinal observational cohort of patients with NAFLD receiving care across the United States.

Randomized placebo-controlled trial of losartan for pediatric NAFLD.

Background And Aims: To date, no pharmacotherapy exists for pediatric NAFLD. Losartan, an angiotensin II receptor blocker, has been proposed as a treatment due to its antifibrotic effects.

Approach And Results: The Nonalcoholic Steatohepatitis Clinical Research Network conducted a multicenter, double-masked, placebo-controlled, randomized clinical trial in children with histologically confirmed NAFLD at 10 sites (September 2018 to April 2020).

Non-Invasive Approaches to Estimate Liver Steatosis and Stiffness in Children With Non-Alcoholic Fatty Liver Disease.

Objectives: To develop pediatric-specific models that predict liver stiffness and hepatic steatosis in non-alcoholic fatty liver disease (NAFLD), based on clinical and laboratory data.

Methods: Children with NAFLD, who had undergone magnetic resonance imaging with proton density fat fraction (MRI-PDFF) for steatosis quantification and/or magnetic resonance elastography (MRE) for liver stiffness assessment were included. We used data from patients imaged between April 2009 to July 2018 to develop a predictive model for fat fraction and stiffness.

Impedance-based measures of muscle mass can be used to predict severity of hepatic steatosis in pediatric nonalcoholic fatty liver disease.

Objectives: The objective of this study was to investigate the association between measures of body composition based on bioelectrical impedance analysis (BIA) and histologic severity of liver disease in a pediatric cohort with nonalcoholic fatty liver disease (NAFLD).

Methods: This was a cross-sectional study of patients < 20 y old with histologically confirmed NAFLD followed in our Steatohepatitis Center from 2017 to 2019. Contemporaneous body-composition data were obtained using a multifrequency octopolar BIA device (InBody 370, InBody, Seoul, South Korea).

Intestinal Guanylate Cyclase-C mRNA Expression in Duodenum and Colon of Children.

Objectives: Guanylate cyclase-C (GC-C) agonists, which increase intestinal secretion and accelerate transit, are used to treat chronic constipation and constipation-predominant irritable bowel syndrome and are being evaluated for pediatric use. Prior studies suggest GC-C receptor density may be higher in young children, potentially amplifying GC-C agonism with treatment implications. We aimed to quantitate duodenal and colonic GC-C mRNA expression in children.