Gestational and Developmental Contributors of Pediatric MASLD.

Pediatric metabolic dysfunction-associated steatotic liver disease (MASLD) is common and can be seen as early as in utero. A growing body of literature suggests that gestational and early life exposures modify the risk of MASLD development in children. These include maternal risk factors, such as poor cardiometabolic health (e.g., obesity, gestational diabetes, rapid weight gain during pregnancy, and MASLD), as well as periconceptional dietary exposures, degree of physical activity, intestinal microbiome, and smoking. Paternal factors, such as diet and obesity, also appear to play a role. Beyond gestation, early life dietary exposures, as well as the rate of infant weight gain, may further modify the risk of future MASLD development. The mechanisms linking parental health and environmental exposures to pediatric MASLD are complex and not entirely understood. In conclusion, investigating gestational and developmental contributors to MASLD is critical and may identify future interventional targets for disease prevention.

Nutritional deficiencies in children.

PURPOSE OF REVIEW: The purpose of this review is to summarize commonly encountered nutritional deficiencies in children and their implications. Considering data suggesting that the majority of children with the United States consume unhealthy diets, the growing interest in the consumption of limiting diets, as well as the insidious clinical presentation of nutritional deficiencies, this is a timely and highly relevant review. RECENT FINDINGS: The underlying socioeconomic and medical circumstances that predispose to nutritional deficiencies in the Western world are covered. The high index of suspicion required to recognize nutritional deficiencies and the limitations of available testing are also discussed. Finally, the need for the development of accurate nutritional biomarkers is presented as a future research priority. SUMMARY: Nutritional deficiencies are not uncommon, even in high resource countries. Clinicians should remain vigilant and include nutritional deficiencies in the differential diagnoses of patients presenting with nonspecific symptoms.

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. Skin lipidomics were performed to explore pathophysiologic mechanisms. RESULTS: Seventy-three patients with histologically confirmed NAFLD completed the Household Food Security Survey Module. Of these, the majority were male (81%) and non-Hispanic (53%), with a mean age at biopsy of 13 ± 3 years. Food insecurity was seen in 42% (n = 31). Comparison of features between food insecure and food secure subgroups revealed no differences in sex, ethnicity, BMI z-score, aminotransferases, or histologic severity. However, children experiencing food insecurity presented on average 2 years before their food secure counterparts (12.3 ± 3.0 vs 14.4 ± 3.6 years, P = .015). A subset of 31 patients provided skin samples. Skin lipidomics revealed that food insecurity was associated with down-regulated features from the lipoamino acid class of lipids, previously linked to inflammation and adipocyte differentiation. CONCLUSIONS: Food insecurity is highly prevalent in children with NAFLD and is associated with earlier presentation. Lipidomic analyses suggest a possible pathophysiologic link that warrants further exploration.

Thermoneutral Housing Enables Studies of Vertical Transmission of Obesogenic Diet-Driven Metabolic Diseases.

Vertical transmission of obesity is a critical contributor to the unabated obesity pandemic and the associated surge in metabolic diseases. Existing experimental models insufficiently recapitulate "human-like" obesity phenotypes, limiting the discovery of how severe obesity in pregnancy instructs vertical transmission of obesity. Here, via utility of thermoneutral housing and obesogenic diet feeding coupled to syngeneic mating of WT obese female and lean male mice on a C57BL/6 background, we present a tractable, more "human-like" approach to specifically investigate how maternal obesity contributes to offspring health. Using this model, we found that maternal obesity decreased neonatal survival, increased offspring adiposity, and accelerated offspring predisposition to obesity and metabolic disease. We also show that severe maternal obesity was sufficient to skew offspring microbiome and create a proinflammatory gestational environment that correlated with inflammatory changes in the offspring in utero and adulthood. Analysis of a human birth cohort study of mothers with and without obesity and their infants was consistent with mouse study findings of maternal inflammation and offspring weight gain propensity. Together, our results show that dietary induction of obesity in female mice coupled to thermoneutral housing can be used for future mechanistic interrogations of obesity and metabolic disease in pregnancy and vertical transmission of pathogenic traits.

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. APPROACH AND RESULTS: We enrolled children with biopsy-proven NAFLD in the Nonalcoholic Steatohepatitis Clinical Research Network within 90 days of liver biopsy. We staged liver fibrosis in consensus using the Nonalcoholic Steatohepatitis Clinical Research Network scoring system. We evaluated existing pediatric and adult models for fibrosis and developed a new pediatric model using the least absolute shrinkage and selection operator with linear and spline terms for discriminating moderate-to-severe fibrosis from none or mild fibrosis. The model was internally validated with 10-fold cross-validation. We evaluated 1055 children with NAFLD, of whom 26% had moderate-to-severe fibrosis. Existing models performed poorly in classifying fibrosis in children, with area under the receiver operator curves (AUC) ranging from 0.57 to 0.64. In contrast, our new model, fibrosis in pediatric NAFLD was derived from fourteen common clinical variables and had an AUC of 0.79 (95% CI: 0.77-0.81) with 72% sensitivity and 76% specificity for identifying moderate-to-severe fibrosis. CONCLUSION: Existing fibrosis prediction models have limited clinical utility in children with NAFLD. Fibrosis in pediatric NAFLD offers improved performance characteristics for risk stratification by identifying moderate-to-severe fibrosis in children with NAFLD.

Prevalence of incidental sonographic findings of hepatic steatosis in children under 4 years of age.

BACKGROUND: The age of onset of nonalcoholic fatty liver disease (NAFLD) and its prevalence in young children is incompletely understood. OBJECTIVE: We sought to evaluate the prevalence of ultrasound findings of hepatic steatosis in a cohort of children less than 4 years of age. MATERIALS AND METHODS: This is an institutional review board-approved retrospective review of ultrasounds performed on children less than 4 years of age from January 2022 to August 2022 at a single quaternary care center. Two independent blinded reviewers evaluated for qualitative and semi-quantitative findings of hepatic steatosis. Per prior literature, hepatorenal index (HRI)>1.75 was used as a threshold suggestive of hepatic steatosis. Chi-square, Mann-Whitney U test, and logistic regression analyses were performed for univariable and multivariable statistical analyses. Kappa statistics were used to assess agreement between reviewers. RESULTS: Eighty-five males and 102 females, median age of 1.1 years (interquartile range 2.1 years), were included. Qualitative findings of hepatic steatosis were seen in 26/187 (14%; 95% CI 10-20%). An HRI>1.75 was present in 15/187 (8%; 95% CI: 5-13%) of examinations, including 11 females and 4 males, and 7/123 (6%) participants <2 years old. Among participants with overweight or obesity, 8/43 (19%) had HRI>1.75 vs. 7/144 (5%) participants without overweight or obesity (P=0.004). Each percentile increase in anthropometrics percentile (weight-to-length or BMI, depending on age) was associated with 22 increased odds of HRI>1.75 (P=0.02). CONCLUSION: Prevalence of sonographic findings of hepatic steatosis in an unselected sample of preschool-age children is 8-14%, and are more common in participants with overweight/obesity.

Weight increase in people with cystic fibrosis on CFTR modulator therapy is mainly due to increase in fat mass.

Background: Ivacaftor, the first CFTR modulator drug, leads to significant long-term improvement in lung function and weight gain. The mechanism as well as the long-term impact of ivacaftor on weight, resting energy expenditure (REE) and body composition remains to be explored. Methods: This prospective observational study included 18 people with CF (pwCF) (age: median (range) 20 (6-58) years) carrying at least one CFTR gating mutation commencing ivacaftor. Assessments of body composition, REE and laboratory investigations were performed at baseline and 6, 12 and 24 months after treatment initiation. Results: Treatment with ivacaftor was associated with a significantly positive change in BMI z-score at 24 months. Fat mass (mean (95% CL) of 6.5 kg (4.0; 9.0) from baseline, p = 0.0001), but not fat-free mass changed under ivacaftor treatment. There was a significant positive correlation between weight and fat mass change. Overall, there was no significant change in measured REE from baseline (mean (95% CL) of 108 kcal/d (-12; 228), p = 0.07) in our cohort. Pancreatic function and other nutritional markers did not change with treatment, with the exception of an increase in serum vitamin A levels (p = 0.006). Conclusion: The weight gain observed in ivacaftor treated pwCF is predominantly secondary to increases in fat mass warranting early counseling of people starting on CFTR-modulating treatment with respect to healthy diet and physical exercise.

Age-related trajectory of bone density in children with intestinal failure: A longitudinal retrospective cohort study.

BACKGROUND: Longitudinal changes in bone health in children with intestinal failure (IF) are unclear. We aimed to better understand the trajectory of bone mineral status over time in children with IF and identify clinical factors that influence the trajectory. METHODS: Clinical records of patients attending the Intestinal Rehabilitation Center of Cincinnati Children's Hospital Medical Center between 2012 and 2021 were reviewed. Children diagnosed with IF before age 3 years with at least two lumbar spine dual-energy x-ray absorptiometry scans were included. We abstracted information on medical history, parenteral nutrition, bone density, and growth. We calculated bone density z scores with and without adjustment for height z scores. RESULTS: Thirty-four children with IF met inclusion criteria. Children were shorter than average with a mean height z score of -1.5 ± 1.3. The mean bone density z score was -1.5 ± 1.3 with 25 of the cohort having a z score < -2.0. After height adjustment, the mean bone density z score was -0.42 ± 1.4 with 11% below -2.0. Most dual-energy x-ray absorptiometry scans (60%) had a feeding tube artifact. Bone density z scores increased slightly with age and lower parenteral nutrition dependency and were higher in scans without an artifact. Etiologies of IF, line infections, prematurity, and vitamin D status were not associated with height-adjusted bone density z scores. CONCLUSION: Children with IF were shorter than expected for age. Deficits in bone mineral status were less common when adjusting for short stature. Etiologies of IF, prematurity, and vitamin D deficiency were not associated with bone density.

Presence of Alpha 1 Antitrypsin Risk Variants is Not Associated With Histologic Severity of Pediatric NAFLD.

BACKGROUND: Among adults with nonalcoholic fatty liver disease (NAFLD), alpha-1-antitrypsin (A1AT) heterozygosity has been linked to advanced liver disease; pediatric data remain unclear. OBJECTIVE: The objective of this study is to determine whether A1AT PiZ or PiS variants are associated with liver disease severity in youth with NAFLD. METHODS: Retrospective study of youth with confirmed NAFLD. Multivariable logistic regression used to determine independent associations between A1AT risk variants and histologic severity [NAFLD activity score (NAS) ≥5 and/or significant fibrosis (stage ≥2)]. RESULTS: The cohort included 269 patients, mean age 12 [±3] years with NAFLD and A1AT phenotyping (n = 260) and/or A1AT levels (n = 261). The mean NAS of the cohort was 4.2 [±1.5]; 50% had any, and 18% had significant fibrosis. Most (86%) had the MM A1AT phenotype, while 7% had the MS and 3% the MZ phenotype (the rest had other, nonpathogenic variants). Mean A1AT level was 123 mg/dL [±20]. A1AT levels did not differ by low versus high NAS (122 ± 2 vs 126 ± 19 mg/dL, P = 0.12) or by no/mild versus significant fibrosis (123 ± 20 vs 126 ± 20 mg/dL, P = 0.23, respectively). Carriers and noncarriers of the PiS or PiZ variants had similar NAS (mean NAS 3.8 ± 1.6 vs 4.2 ± 1.4; P = 0.25, respectively). Fibrosis severity did not differ by carrier vs noncarrier group: 38% versus 52% had any fibrosis ( P = 0.17) and 14% versus 18% had significant fibrosis ( P = 0.80, respectively). Multivariable modeling showed no association between A1AT risk variants and histologic severity. CONCLUSION: While not uncommon, carriage of the A1AT PiZ or PiS risk variants was not associated with histologic severity 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.

Background: 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. Methods: This prospective study recruited participants with known or suspected NAFLD who underwent a research VCTE examination (FibroScan Mini 430). Ten valid VCTE liver stiffness measurements (kPa) and controlled attenuation parameter (CAP) (dB/m) measurements were obtained for each participant. Available clinically acquired MR elastography and magnetic resonance imaging proton density fat fraction (PDFF), liver ultrasound shear wave elastography, and biopsy served as references standards. Results: Eighty-four consecutive participants were included (55 males, mean age 15.0 ± 3.5 years, mean BMI 36.6 ± 9.4 kg/m2). VCTE examinations were complete in 80/83 participants. 37/83 participants were examined with an XL probe. There was no significant correlation between CAP and PDFF [n = 16; r = 0.17 (95% confidence interval [CI]: -0.34 to 0.61), p = 0.5] or between VCTE liver stiffness and MR elastography stiffness [n = 27; r = 0.31 (95% CI: -0.07 to 0.62), p = 0.10]. For prediction of any fibrosis stage ≥1 on biopsy (n = 9/15 participants), VCTE median liver stiffness >5.1 kPA had an area under receiver operating characteristic curve of 0.52 (95% CI: 0.26-0.78) with a sensitivity of 88.9% and specificity of 16.6% (p > 0.99). Conclusions: Complete VCTE examinations could be obtained in most pediatric patients with NAFLD. Neither VCTE liver stiffness nor CAP correlated well with measures of liver fat or stiffness by established imaging modalities and biopsy.

BMI Metrics Are Poor Predictors of Pediatric Nonalcoholic Fatty Liver Disease Severity.

Background: Alternative BMI metrics are superior to BMI z score (BMIz) in tracking obesity but have not been evaluated in patients with nonalcoholic fatty liver disease (NAFLD). Our objective was to evaluate whether BMI-adjusted z score (BMIaz) or BMI expressed as a percentage of the 95th percentile (%BMIp95) are better predictors of degree of alanine aminotransferase (ALT) elevation, a surrogate for NAFLD severity, compared with BMIz in patients with NAFLD. Methods: A retrospective study of 776 subjects aged 2-18 years with BMIz > 1.0 followed in a NAFLD subspecialty clinic was conducted. Regression analysis was used to determine predictors of elevated ALT. Results: There was no association between BMIz, BMIaz, or %BMIp95 and degree of ALT elevation using linear or logistic regression. Conclusion: These results do not support the use of alternative BMI metrics for evaluating NAFLD severity. Future studies should investigate longitudinal assessments and correlation with histology.

Nonalcoholic Fatty Liver Disease in Young Children with Obesity.

Background: To evaluate the prevalence of suspected nonalcoholic fatty liver disease (NAFLD) in young children with obesity and determine associated risk factors. Methods: Retrospective single-center study of children with obesity, ages 2-6 years. Suspected NAFLD was defined as an alanine aminotransferase (ALT) >30 U/L. Multivariable analyses were performed to determine predictors of elevated ALT. Results: Among 237 children 2-6 years old, 35% had elevated ALT. Multivariable analysis showed that higher BMI z score [odds ratio (OR): 1.5 confidence interval (95% CI: 1.04-1.92)] and higher gamma-glutamyl transferase (GGT) [OR: 21.3 (95% CI: 3.7-121.1)] predicted elevated ALT. Of those with ≥2 ALT levels, 38% (n = 33/86) had a persistently elevated ALT (median ALT >30 U/L). Only 7% of patients with ALT >30 U/L underwent further testing to evaluate for alternative causes of liver disease. Conclusion: Suspected NAFLD is common in young children with obesity and predicted by obesity severity and GGT. Other cardiometabolic markers were equivalent between those with normal vs. elevated ALT, suggesting NAFLD onset may precede development of comorbidities. Earlier screening will enable prompt diagnosis and intervention, which may prevent or delay the onset of cardiometabolic diseases commonly associated with NAFLD in adolescence and adulthood.

Clinically Meaningful Body Mass Index Change Impacts Pediatric Nonalcoholic Fatty Liver Disease.

OBJECTIVE: To investigate the prevalence and characteristics of children with nonalcoholic fatty liver disease (NAFLD) who reduce their body mass index (BMI) z-score (BMIz) by >.25, a goal in obesity medicine, and to determine the BMIz decrease needed for serum aminotransferase normalization. STUDY DESIGN: This retrospective, single-center study included patients aged <18 years followed for NAFLD. Patients who had undergone weight loss surgery or had other reasons for weight loss/gain were excluded. Logistic regression was used to determine the odds of achieving a BMIz change of >-.25, as well as predictors of this outcome. RESULTS: Of the 784 children who met the study criteria (median age, 13 years; 66% male; 24% Hispanic), 541 had a lowest BMIz at >90 days following the baseline clinic visit. Of these children, 168 (31%) had a BMIz change of >-.25 from baseline over a median of 367 days (IQR, 201-678 days). Decreases in serum aminotransferase and lipid levels were seen in both groups (with and without a BMIz change of >-.25); however, these decreases were more pronounced in children who achieved a BMIz drop of >.25. Hemoglobin A1c concentration did not change in either group. Young age (OR, .861; 95% CI, .81-.92; P < .01) and non-Hispanic ethnicity (OR of non-Hispanic vs Hispanic, .61; 95% CI, .38-.97; P < .04) were predictors of a BMIz change >-.25. The BMIz decrease associated with normalization of serum alanine aminotransferase was .27. CONCLUSIONS: A BMIz reduction of >.25 is associated with significant changes in serum aminotransferase levels. These findings can further guide the clinical management of children with NAFLD.

Health-Related Social Needs Facing Youth with NonAlcoholic Fatty Liver Disease.

Background: The objective of this study was to identify the prevalence of health-related social needs among youth with nonalcoholic fatty liver disease (NAFLD). Methods: Retrospective review of prospectively administered health-related social needs questionnaires from Steatohepatitis Clinics. Results: Patients with NAFLD (n=271) were predominantly male (72%), and non-Hispanic (68%). The most common unmet need was food insecurity (13%, n=36). Families who endorsed food insecurity at the first visit were 27-fold more likely to have unmet health-related social needs persist at subsequent visits than those who were food-secure at their first visit (95% CI: 6.7-111). Conclusion: Screening for social, economic, and environmental needs may identify previously unrecognized family challenges and may enhance intervention delivery, inform resource allocation, and improve outcomes.

American Association of Clinical Endocrinology Clinical Practice Guideline for the Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Primary Care and Endocrinology Clinical Settings: Co-Sponsored by the American Association for the Study of Liver Diseases (AASLD).

OBJECTIVE: To provide evidence-based recommendations regarding the diagnosis and management of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) to endocrinologists, primary care clinicians, health care professionals, and other stakeholders. METHODS: The American Association of Clinical Endocrinology conducted literature searches for relevant articles published from January 1, 2010, to November 15, 2021. A task force of medical experts developed evidence-based guideline recommendations based on a review of clinical evidence, expertise, and informal consensus, according to established American Association of Clinical Endocrinology protocol for guideline development. RECOMMENDATION SUMMARY: This guideline includes 34 evidence-based clinical practice recommendations for the diagnosis and management of persons with NAFLD and/or NASH and contains 385 citations that inform the evidence base. CONCLUSION: NAFLD is a major public health problem that will only worsen in the future, as it is closely linked to the epidemics of obesity and type 2 diabetes mellitus. Given this link, endocrinologists and primary care physicians are in an ideal position to identify persons at risk on to prevent the development of cirrhosis and comorbidities. While no U.S. Food and Drug Administration-approved medications to treat NAFLD are currently available, management can include lifestyle changes that promote an energy deficit leading to weight loss; consideration of weight loss medications, particularly glucagon-like peptide-1 receptor agonists; and bariatric surgery, for persons who have obesity, as well as some diabetes medications, such as pioglitazone and glucagon-like peptide-1 receptor agonists, for those with type 2 diabetes mellitus and NASH. Management should also promote cardiometabolic health and reduce the increased cardiovascular risk associated with this complex disease.

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 = 15.8 years; Mean BMI = 37 kg/m 2 ) participated in focus groups. To supplement qualitative data, adolescents and their caregiver completed measures assessing illness perceptions, adolescent quality of life, and eating/activity behaviors. RESULTS: Focus group themes suggested reactions to diagnosis varied from unconcerned to anxious. NAFLD diagnosis occurred within the context of other psychological/medical concerns and was not perceived to affect most adolescents' daily lives. Although adolescents understood general contributors to NAFLD, comprehension of their diagnosis varied. Adolescents were more likely to make lifestyle changes when families were supportive, and they preferred tailored recommendations for health behavior change from the healthcare team. Notably, 62.5% of adolescents were more concerned about their weight than NAFLD. Almost half (43.8%) identified as food insecure. CONCLUSIONS: Adolescents with NAFLD may benefit from personalized treatment. Care could be enhanced by ensuring comprehension of diagnosis, problem-solving personal, and family barriers and increasing family support. Harnessing adolescents' desire for weight loss may be a more salient driver for change in disease status. Interventions should also address systemic barriers such as food insecurity to ensure equitable care.

Nutritional outcomes of patients with pediatric and congenital heart disease requiring ventricular assist devices.

BACKGROUND: Ventricular assist devices (VADs) support children with heart failure. The objective is to report on the nutrition outcomes of children requiring VAD. METHODS: This was a retrospective study performed in a tertiary care center. All patients undergoing VAD placement from 2010 to 2018 were included. Exclusion criteria were VAD placement in outside hospitals, missing baseline anthropometrics, and death in the first 15 days post-VAD. Clinical, demographic, and nutrition data were collected from baseline and at 2 months post-VAD. Descriptive statistics were used. RESULTS: Of the 52 patients who had undergone VAD placement, 49 (65% male, 80% with cardiomyopathy; median age at VAD, 8 years) met the study criteria. The median length of stay following VAD was 63 days. Eight patients (16%) had malnutrition at baseline (five mild, two moderate, and one severe). At 2 months post-VAD, seven (of 49) patients had undergone heart transplantation and three (6%) were deceased. The proportion of patients with malnutrition was significantly different at 2 months post-VAD (P = 0.009), with six patients showing evidence of malnutrition (three mild, two moderate, and one severe; body mass index z score at baseline vs 2 months: 0.11 (± 1.72) vs 0.43 (± 0.94), P = 0.049). The percent of required energy consumed increased from 77% at baseline to 90% at 2 months post-VAD (P = 0.021). The proportion of patients fed solely enterally also increased (62% vs 84%, respectively; P = 0.042). CONCLUSION: VADs are associated with improved nutrition outcomes. Future studies should investigate the impact of VADs on body composition and longer-term outcomes.

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). Inclusion criteria were age 8-17 years, histologic NAFLD activity score ≥ 3, and serum alanine aminotransferase (ALT) ≥ 50 U/l. Children received 100 mg of losartan or placebo orally once daily for 24 weeks. The primary outcome was change in ALT levels from baseline to 24 weeks, and the preset sample size was n = 110. Treatment effects were assessed using linear regression of change in treatment group adjusted for baseline value. Eighty-three participants (81% male, 80% Hispanic) were randomized to losartan (n = 43) or placebo (n = 40). During an enrollment pause, necessitated by the 2019 coronavirus pandemic, an unplanned interim analysis showed low probability (7%) of significant group difference. The Data and Safety Monitoring Board recommended early study termination. Baseline characteristics were similar between groups. The 24-week change in ALT did not differ significantly between losartan versus placebo groups (adjusted mean difference: 1.1 U/l; 95% CI = -30.6, 32.7; p = 0.95), although alkaline phosphatase decreased significantly in the losartan group (adjusted mean difference: -23.4 U/l; 95% CI = -41.5, -5.3; p = 0.01). Systolic blood pressure decreased in the losartan group but increased in placebo (adjusted mean difference: -7.5 mm Hg; 95% CI = -12.2, -2.8; p = 0.002). Compliance by pill counts and numbers and types of adverse events did not differ by group. CONCLUSIONS: Losartan did not significantly reduce ALT in children with NAFLD when compared with placebo.

Body composition measured by bioelectrical impedance analysis is a viable alternative to magnetic resonance imaging in children with nonalcoholic fatty liver disease.

OBJECTIVE: To determine the relationship between bioelectrical impedance analysis (BIA) and magnetic resonance imaging (MRI) obtained measures of body composition in children with nonalcoholic fatty liver disease (NAFLD). METHODS: Youth with obesity and NAFLD who had BIA and abdominal MRI testing were included. BIA measured skeletal muscle mass (SMM), appendicular lean mass (ALM), trunk muscle mass (TMM), and percent body fat. MRI measured total psoas muscle surface area (tPMSA) and fat compartments. Univariate analysis described the relationship between BIA- and MRI-derived measurements. Multivariable regression analyses built a model with body composition measured via MRI. RESULTS: 115 patients (82 (71%) male, 38 (33%) Hispanic, median age14 years) were included. There was a strong correlation between tPMSA and SMM, ALM, and TMM (correlation coefficients [CCs]: 0.701, 0.689, 0.708, respectively; all P < .001). Higher SMM, ALM, and TMM were associated with higher tPMSA. This association remained after controlling for age, sex, ethnicity, type 2 diabetes mellitus status, and body mass index z-score. Total fat mass by BIA and MRI-determined total, subcutaneous, and intraperitoneal fat area correlated significantly (CCs: 0.813, 0.808, 0.515, respectively; all P < .001). In univariate regression, higher total fat mass by BIA was associated with increased total fat area and increased fat in each of the four regions measured by MRI. After controlling for confounders, the association between total fat mass by BIA and total fat area by MRI persisted. CONCLUSIONS: BIA measures of muscle and fat mass correlate strongly with MRI measures of tPMSA and fat areas in children with obesity and NAFLD.