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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.Children with NAFLD enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network were followed longitudinally. Incidence of T2D was determined by using clinical history and fasting laboratory values. Cumulative incidence curves were developed for time to T2D. A Cox regression multivariable model was constructed using best subsets Akaike's Information Criteria selection.This study included 892 children with NAFLD and with a mean age of 12.8 years (2.7) followed for 3.8 years (2.3) with a total 3234 person-years at risk. The incidence rate of T2D was 3000 new cases per 100,000 person-years at risk. At baseline, 63 children had T2D, and during follow-up, an additional 97 children developed incident T2D, resulting in a period prevalence of 16.8%. Incident T2D was significantly higher in females versus males (hazard ratio [HR], 1.8 [1.0-2.8]), associated with BMI z-score (HR, 1.8 [1.0-3.0]), and more severe liver histology including steatosis grade (HR, 1.3 [1.0-1.7]), and fibrosis stage (HR, 1.3 [1.0-1.5]).Children with NAFLD are at high risk for existing and incident T2D. In addition to known risk factors for T2D (female and BMI z-score), severity of liver histology at the time of NAFLD diagnosis was independently associated with T2D development. Targeted strategies to prevent T2D in children with NAFLD are needed.

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.

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. While 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.

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.This retrospective, single-center study included patients aged18 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.Of the 784 children who met the study criteria (median age, 13 years; 66% male; 24% Hispanic), 541 had a lowest BMIz at90 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.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.

BACKGROUND & AIMS: A subset of patients with non-alcoholic steatohepatitis (NASH) respond to treatment with vitamin E. The characteristics of responders are not known. The objective of this study was to investigate the outcomes of vitamin E use in clinical practice and to determine factors associated with response to treatment. METHODS: A pediatric cohort with NASH treated with vitamin E for 6–24 months was studied retrospectively. Vitamin E response was defined as serum alanine aminotransferase (ALT) normalization or >50% ALT reduction from baseline. Univariate and multivariate backward logistic regression was used to determine the clinical, biochemical and histologic predictors of response to vitamin E. Available paired liver biopsy data were analyzed to determine histologic response. RESULTS: Of the 151 children prescribed vitamin E, 73 met inclusion/exclusion criteria. Of those 28 (38%) were vitamin E responders. Higher baseline serum alkaline phosphatase (ALP) levels, steatosis grade and NAFLD Activity Score (NAS) were associated with response to vitamin E (ALP: odds ratio (OR), 14.1; 95% confidence interval (CI), 1.7–118.6; steatosis: OR 2.5, 95%CI, 1.2–5.0; NAS: OR 1.6, 95%CI, 1.1–2.4). In a multivariate stepwise logistic regression model, ALP and steatosis grade rendered an area under the curve of 0.75 (p

To investigate the effect of high fructose diet on ultrastructure and content of hepatic mitochondria, we randomized 6-8 weeks old male C57Bl6/J mice to ad lib chow or high-fat-high-fructose (HF2) diet for 32 weeks. HF2-fed mice gained more weight, had higher plasma alanine aminotransferase, and fasting glucose levels and increased hepatic triglyceride content at all time points compared to chow-fed mice. HF2-fed mice had lower mitochondrial to nuclear DNA ratio compared to chow-fed mice. HF2-fed mice had lower average mitochondrial surface area and the number of mitochondria compared to chow-fed mice. HF2-fed mice had higher expression of the hepatic endoplasmic reticulum stress marker Chop, compared to chow-fed mice. A diet high in fat and fructose leads to enhanced hepatic mitochondrial aging, depletion, and dysfunction, which may be important determinants of nonalcoholic steatohepatitis pathogenesis.

OBJECTIVES The aim of the study was to determine whether pediatric patients with nonalcoholic fatty liver disease (NAFLD) exposed to psychotropic medications have more severe liver disease compared to their counterparts who are not on these medications. We hypothesize that use of psychotropic agents is associated with liver disease severity. METHODS Children and adolescents with biopsy-confirmed NAFLD were included in this study. Histology data, detailed clinical information, and results of serum biochemistries performed within 3 months of the liver biopsy were collected retrospectively. Univariate and multivariate modeling was used to determine differences between the groups and to control for confounders. RESULTS A total of 228 patients were included, 17 (8%) of whom where on psychotropic medications at the time of the liver biopsy. Patients on psychotropic medications were more likely to also be on metformin (53% vs 18%, P

Serum immunoglobulin A (IgA) is a biomarker of liver disease severity in adult nonalcoholic fatty liver disease (NAFLD). The objective of this study was to assess whether this is true in pediatric NAFLD. This was a retrospective study of children followed in the Steatohepatitis Center of a tertiary care center (2010-2017). Serum IgA levels, histology and biochemical markers of hepatocellular injury and metabolic dysregulation were collected. Of the 600 children with available serum IgA levels (mean age 14 ± 3 years, 62% boys, 80% non-Hispanic), IgA was elevated in 4%. The group with elevated IgA levels was younger and had a greater representation of Hispanic ethnicity compared with those with normal or low IgA. Body mass index and aminotransferases were not different between the groups. Histology was available for 170 children and was not different in those with elevated, normal and low IgA. In contrast to adults, serum IgA is not a biomarker of liver disease severity in pediatric NAFLD.

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.

OBJECTIVES: To determine the prevalence of alternative causes of liver disease in a cohort of youth with overweight and obesity undergoing evaluation for suspected nonalcoholic fatty liver disease (NAFLD). METHODS: Multicenter, retrospective cohort study of patients aged ≤18 years with overweight and obesity and evidence of elevated serum aminotransferases and/or hepatic steatosis on imaging, referred for suspected NAFLD to Cincinnati Children’s Hospital Medical Center (2009–2017) or Yale New Haven Children's Hospital (2012–2017). Testing was performed to exclude the following: autoimmune hepatitis (AIH), Wilson disease, viral hepatitis (B and C), thyroid dysfunction, celiac disease, α-1 antitrypsin deficiency, and hemochromatosis. RESULTS: A total of 900 children with overweight and obesity (63% boys, 26% Hispanic ethnicity) were referred, with a median age of 13 years (range: 2–18). Most had severe obesity (n = 666; 76%) with a median BMI z score of 2.45 (interquartile range [IQR]: 2.2–2.7). Median alanine aminotransferase level at presentation was 64 U/L (IQR: 42–95). A clinically indicated liver biopsy was performed in 358 children (40%) at a median of 6 months (IQR: 1–14) post initial visit; of those, 46% had confirmed nonalcoholic steatohepatitis. Positive autoantibodies were observed in 13% of the cohort, but none met criteria for AIH. Only 19 (2%) were found to have other causes of liver disease, with no cases of viral hepatitis or Wilson disease detected. CONCLUSIONS: In a large, multicenter cohort, the vast majority of children with overweight and obesity with presumed or confirmed NAFLD tested negative for other causes of liver disease. In contrast to a previous pediatric report, no patient was diagnosed with AIH.

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 confi(rmed 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). BIA data collected were skeletal muscle mass, appendicular muscle mass, and percentage body fat. Skeletal and appendicular muscle mass were corrected for height (dividing by the square of height), generating their respective indices. Univariate linear and logistic regression, followed by multivariable logistic regression analyses, were used. RESULTS: Of the 79 children included (27% female, 73% male; 38% Hispanic; median age, 13 y; median body mass index Z-score, 2.43), the median NAFLD Activity Score was 4 (interquartile range, 3–5). In multivariable regression analyses, the skeletal muscle mass index was negatively associated with hepatic steatosis after controlling for confounders (odds ratio, 0.76; 95% confidence interval, 0.62–0.93). Similarly, the appendicular muscle mass index was negatively associated with severity of hepatic steatosis severity (odds ratio, 0.69; 95% confidence interval, 0.53–0.90). In contrast, percentage body fat was not associated with hepatic steatosis. NAFLD Activity Score, lobular inflammation, ballooning scores, and fibrosis stage were not associated with measures of body composition. CONCLUSIONS: There is an inverse association between BIA-based measures of muscle mass and severity of hepatic steatosis in children with NAFLD. BIA data could further inform clinical decision making in this context

Background Autoantibodies are frequently positive in adults with nonalcoholic fatty liver disease (NAFLD) without concurrent autoimmune hepatitis (AIH). The clinical significance of this is unknown in children. Objective To determine the prevalence of autoantibody positivity in pediatric NAFLD and to evaluate its association with disease severity. Methods Multicenter, retrospective study of patients ≤18 years of age with biopsy-confirmed NAFLD. Descriptive statistics were used and groups were compared using Wilcoxon-Mann Whitney or χ2 testing, and multivariable logistic regression was used for binary or ordinal outcomes. Results One hundred and thirty six patients with a median age of 14 years were included. The median body mass index Z-score was 2.5 (interquartile range 2.2, 2.6). Positive antinuclear antibody (ANA), anti-smooth muscle antibody (ASMA), anti-liver-kidney microsomal antibody, or any combination of autoantibodies were observed in 22%, 14%, 0%, and 33% of patients, respectively. The proportion of patients with a steatosis score ≥2 was significantly higher in those with positive ANA (P = .045). In the multivariable regression analysis, positive ANA was associated with increased odds of steatosis score ≥2 (odds ratio, 5.91; 95% confidential interval, 1.50-23.26), after controlling for potential confounders. No other significant histology differences were seen between the groups. Conclusions Positive ANA and ASMA are common in children with NAFLD; however, anti-LKM positivity is not. ANA positivity is associated with more severe steatosis.

BACKGROUND AND AIMS: Longitudinal studies on childhood predictors of Nonalcoholic Fatty Liver Disease (NAFLD) progression are lacking. The objective of this study was to determine whether baseline clinical or laboratory measures predict liver disease outcomes in a pediatric NAFLD cohort. METHODS: Retrospective study of patients with presumed NAFLD using baseline and follow up clinical and laboratory measures. Disease outcomes were defined using the mean serum alanine aminotransferase (ALT) levels from 24-36 months after first visit. Logistic regression assessed the relationship between ALT progression/regression and predictor variables. Multivariable regression determined the best model for predicting the ALT outcome. Markov process modeling explored the likelihood for a patient to transition between ALT states. RESULTS: 816 patients identified, 144 had sufficient data at 24-36 months and 567 had paired ALT data over any 12 month period. Regression was seen in 26%, while 30% progressed. No baseline clinical or laboratory measurements had significant effect on disease outcomes. Markov modeling demonstrated that subjects were more likely to remain in their baseline ALT group or to worsen, than to improve. CONCLUSIONS: Routinely obtained baseline clinical or laboratory measures cannot help risk-stratify youth with presumed NAFLD in terms of long-term outcomes. Close clinical, radiographic, and histologic evaluation of patients is warranted to determine those at risk of progression.

OBJECTIVES: To determine the prevalence of renal impairment in a large cohort of youths with histologically confirmed nonalcoholic fatty liver disease (NAFLD), and to determine its association with liver disease severity. STUDY DESIGN: Clinical, laboratory, and histology data were collected retrospectively in a pediatric cohort with biopsy-confirmed NAFLD at a tertiary care center between 2010 and 2017. Histological NAFLD severity was scored using validated criteria. Glomerular filtration rate (GFR) was calculated and categorized as low (136 mL/min/1.73 m(2)). Univariate and multivariate modeling were used to determine differences between the GFR groups and to control for confounders. RESULTS: The cohort comprised 179 patients (82% non-Hispanic; median age; 14 years; IQR, 12–16 years). One-third of the patients had abnormal renal function, including 36 (20%) with glomerular hyperfiltration and 26 (15%) with low GFR. In multivariable logistic regression, compared with normal GFR, hyperfiltration was independently associated with higher NAFLD activity score (aOR, 2.96; 95% CI, 1.49–5.87; P = .002), after adjusting for age, sex, ethnicity, obesity severity, presence of type 2 diabetes mellitus, and medications. CONCLUSIONS: In this large cohort with histologically confirmed NAFLD, renal impairment was highly prevalent and associated with liver disease severity, independent of obesity severity. Screening patients with confirmed NAFLD for renal complication is recommended.

OBJECTIVE: To assess liver disease progression using paired magnetic resonance imaging (MRI) measurements of liver fat fraction (FF) and stiffness. STUDY DESIGN: Retrospective cohort study including patients with nonalcoholic fatty liver disease who had undergone repeat MRI studies. Descriptive statistics were used, as well as Pearson or Spearman correlation when appropriate. Mixed model analyses were used to determine relationships between liver FF/stiffness and predictor variables. RESULTS: Sixty-five patients (80% non-Hispanic, mean age 14 ± 3 years) were included. Time from first to last MRI was 27 ± 14 months. Over time, body mass index z score remained stable, and there were no significant differences in mean serum aminotransferases, insulin, glucose, triglycerides, low-density lipoprotein, and high-density lipoprotein (HDL) levels. However, the proportion of patients with alanine aminotransferase (ALT) < 50 U/L increased. MRI FF and stiffness decreased in 29% and 20% of patients, respectively, and increased in 25% and 22% of patients, respectively. There was a weak positive correlation between FF change and ALT change (r = 0.41, P = .053) and a moderate negative correlation between change in FF and change in serum HDL levels (r = −0.58, P = .004). After adjusting for HDL, increase in serum insulin was the only variable predictive of increase in FF (P = .061). There was no correlation between change in liver stiffness and change in ALT (r = .02, P = .910). CONCLUSIONS: MRI-determined hepatic FF and stiffness improved in a minority of patients overtime. ALT levels were not reflective of the change in FF or stiffness. MRI-based imaging is complementary in the assessment of NAFLD progression.

BACKGROUND AND OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is linked to obesity. Obesity is associated with lower socioeconomic status (SES). An independent link between pediatric NAFLD and SES has not been elucidated. The objective of this study was to evaluate the distribution of socioeconomic deprivation, measured using an area-level proxy, in pediatric patients with known NAFLD and to determine whether deprivation is associated with liver disease severity. METHODS: Retrospective study of patients

BACKGROUND: Paediatric non-alcoholic fatty liver disease (NAFLD) is highly prevalent among children with obesity. The primary objective of this study was determining whether obesity severity is associated with NAFLD severity. By using paediatric classifications for severe obesity, clinicians may be able to better risk stratify patients, which in turn would guide more effective management and treatment. METHODS: Retrospective cohort study including patients followed at Cincinnati Children's Medical Center for NAFLD. Patients were categorized as overweight or class I, II, III obese based on established body mass index (BMI) cut-offs. Liver disease severity was determined using biochemical, imaging (magnetic resonance elastography [MRE]), and histologic evidence of liver injury. RESULTS: Three cohorts were studied individually based on the method used to assess disease severity (biochemical n = 767, imaging n = 366, and histology n = 249). Between the three cohorts, there were significant differences in age, proportion of patients with class II and class III obesity, and serum alanine transaminase (ALT) levels. In the biochemistry cohort, the odds of having ALT > 80 U/L were highest in patients with class III obesity (P = .026). In the imaging cohort, liver stiffness was significantly different between BMI groups of patients (P = .001). In the histology cohort, those with class III obesity had significantly higher odds of NAFLD activity score (NAS) ≥ 5 (P = .012). DISCUSSION: Obesity severity is associated with liver disease severity. Patients with more severe obesity are more likely to have more advanced liver disease, a finding that can assist in risk stratification, as well as monitoring and treatment approaches.

BACKGROUND/OBJECTIVES: To determine associations between serum 25-hydroxyvitamin D (25(OH)-D) concentrations and histologic nonalcoholic fatty liver disease (NAFLD) severity. SUBJECTS/METHODS: Clinical, laboratory, and histology data were collected retrospectively in a pediatric cohort with biopsy-confirmed NAFLD. Serum 25(OH)-D concentrations were used to define vitamin D deficiency (≤20 ng/ml), insufficiency (21–30 ng/ml), and sufficiency (≥31 ng/ml). RESULTS: In all, 234 patients (78% non-Hispanic, median age 14 years) were included. The majority (n = 193) were either vitamin D insufficient (50%) or deficient (32%). Eighty-four patients (36%) reported taking vitamin D supplements at the time of biopsy; serum 25(OH)-D concentrations were not higher in those supplemented. There were no differences in the demographic, clinical, and laboratory characteristics of the three vitamin D status groups. Severity of steatosis, ballooning, lobular/portal inflammation, and NAFLD activity score were also not different between the groups. The proportion of patients with significant fibrosis (stage ≥ 2) was higher in those with insufficiency (29%) compared to those who were sufficient (17%) or deficient (15%, p = 0.04). After controlling for important covariates selected from age, body mass index, ethnicity, vitamin D supplementation, and season, the insufficient group had increased odds of a higher fibrosis score compared to the sufficient group (adjusted OR, 2.04; 95%CI, 1.02–4.08). CONCLUSIONS: Vitamin D deficiency and insufficiency are common in children with NAFLD, but not consistently related with histologic disease severity. Prospective longitudinal studies are needed to determine optimal dosing strategies to achieve sufficiency and to determine whether adequate supplementation has an impact on histology.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most common pediatric chronic liver disease. Little is known about outcomes in recognized youth. METHODS: We compared paired liver biopsies from 122 of 139 children with NAFLD (74% male; 64% white; 71% Hispanic; mean age, 13 ± 3 years; age range, 8–17 years) who received placebo and standard of care lifestyle advice in 2 double-blind, randomized clinical trials within the nonalcoholic steatohepatitis (NASH) clinical research network from 2005 through 2015. We analyzed histologic changes with respect to baseline and longitudinal change in clinical variables using regression analysis. RESULTS: At enrollment, 31% of the children had definite NASH, 34% had borderline zone 1 NASH, 13% had borderline zone 3 NASH, and 21% had fatty liver but not NASH. Over a mean period of 1.6 ± 0.4 years, borderline or definite NASH resolved in 29% of the children, whereas 18% of the children with fatty liver or borderline NASH developed definite NASH. Fibrosis improved in 34% of the children but worsened in 23%. Any progression to definite NASH or in fibrosis occurred in 36% of the children, and both occurred in 11% of the children. Any improvement in NASH or fibrosis occurred in 52%, and both occurred in 20% of children. Type 2 diabetes developed in 5% of the cohort. Any progression to NASH and/or fibrosis was associated with adolescent age, higher waist circumference, levels of alanine or aspartate aminotransferase, total and low-density lipoprotein-cholesterol at baseline, increasing level of alanine aminotransferase, and hemoglobin A1C (P < .05). Progression to NASH and/or fibrosis were also associated with increasing level of gamma-glutamyl transferase and development of type 2 diabetes (P < .01). Increasing level of gamma-glutamyl transferase also associated with reduced odds of any improvement (P = .003). CONCLUSIONS: One-third of children with NAFLD enrolled in placebo groups of clinical trials had histologic features of progression within 2 years, in association with increasing obesity and serum levels of aminotransferases and loss of glucose homeostasis.

OBJECTIVE: To investigate the association between muscle mass and liver disease severity in pediatric patients with non-alcoholic fatty liver disease (NAFLD). STUDY DESIGN: This was a retrospective study of patients aged

The purpose of this study is to determine the relationships between quantitative liver MRI measurements and liver biopsy findings in pediatric and young adult patients with nonalcoholic fatty liver disease (NAFLD).Data were obtained from a registry that prospectively enrolls pediatric and young adult patients with biopsy-confirmed NAFLD at our tertiary medical center with parent or guardian and subject informed consent, as appropriate. Patients enrolled between November 2007 and June 2016 with a quantitative liver MRI examination within 6 months of biopsy were included (n = 69). Liver stiffness (kilopascals), volume (milliliters), and fat fraction (percentage) were extracted from MRI records. Multiple linear regression was used to determine the relationships between NAFLD activity score and quantitative MRI measures, and between MRI liver stiffness and histopathologic scores (steatosis, lobular inflammation, portal inflammation, hepatocyte ballooning, and fibrosis). Histopathologic data were extracted from medical records, with severity graded by hepatopathologists using Non-alcoholic Steatohepatitis (NASH) Clinical Research Network criteria. Ordinal logistic regression was used to assess the relationship between categoric NAFLD severity (simple steatosis vs NASH vs NASH with significant fibrosis) and MRI measures.The mean (± SD) patient age at the time of MRI was 14.3 ± 2.8 years (range, 8-21 years); 25 (36.2%) patients were female. Liver biopsy was performed within a mean of 64.4 days of the MRI examination. There was a positive correlation between histopathologic steatosis and MRI liver fat fraction (ρ = 0.57; p0.0001). MRI fat fraction was the only significant imaging predictor of NAFLD activity score (p = 0.017). Fibrosis score was the only significant histopathologic predictor of MRI liver stiffness (p = 0.001). MRI liver volume was the only imaging predictor of categoric NAFLD severity (odds ratio = 1.001; 95% CI, 1.000-1.002; p = 0.007).There was significant positive correlation between histopathologic and MRI liver fat measurements in our cohort. MRI liver stiffness did not predict the severity of fatty liver disease in children and young adults.

To examine the distribution of birth weight in children with nonalcoholic fatty liver disease (NAFLD) compared with the general US population, and to investigate the relationship between birth weight and severity of NAFLD.A multicenter, cross-sectional study of children with biopsy-proven NAFLD enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network Database. Birth weight was categorized as low birth weight (LBW), normal birth weight (NBW), or high birth weight (HBW) and compared with the birth weight distribution in the general US population. The severity of liver histology was assessed by birth weight category.Children with NAFLD (n = 538) had overrepresentation of both LBW and HBW compared with the general US population (LBW, 9.3%; NBW, 75.8%; HBW, 14.9% vs LBW, 6.1%; NBW, 83.5%; HBW 10.5%; P .0001). Children with HBW had significantly greater odds of having more severe steatosis (OR, 1.82, 95% CI. 1.15-2.88) and nonalcoholic steatohepatitis (OR, 2.03; 95% CI, 1.21-3.40) compared with children with NBW. In addition, children with NAFLD and LBW had significantly greater odds of having advanced fibrosis (OR, 2.23; 95% CI, 1.08-4.62).Birth weight involves maternal and in utero factors that may have long-lasting consequences. Children with both LBW and HBW may be at increased risk for developing NAFLD. Among children with NAFLD, those with LBW or HBW appear to be at increased risk for more severe disease.

BACKGROUND & AIMS: Focal zone 1 steatosis, although rare in adults with nonalcoholic fatty liver disease (NAFLD), does occur in children with NAFLD. We investigated whether focal zone 1 steatosis and focal zone 3 steatosis are distinct subphenotypes of pediatric NAFLD. We aimed to determine associations between the zonality of steatosis and demographic, clinical, and histologic features in children with NAFLD. METHODS: We performed a cross-sectional study of baseline data from 813 children (age less than 18 years; mean age, 12.8±2.7 years). The subjects had biopsy-proven NAFLD and were enrolled in the NASH Clinical Research Network. Liver histology was reviewed using the Nonalcoholic Steatohepatitis Clinical Research Network scoring system. RESULTS: Zone 1 steatosis was present in 18% of children with NAFLD (n=146) and zone 3 steatosis was present in 32% (n=244). Children with zone 1 steatosis were significantly younger (10 vs 14 years; P

Physicians who are recruiting participants for a clinical trial should neither accept undue compensation nor withhold information about the risks and benefits of the trial from patients who meet the enrollment criteria.

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. Standardized dietary recommendations were provided. After 1 year, lipid profiles were repeated and interpreted according to National Heart, Lung, and Blood Institute Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction. Main outcomes were meeting criteria for clinically actionable dyslipidemia at baseline, and either achieving lipid goal at follow-up or meeting criteria for ongoing intervention. RESULTS:There were 585 participants, with a mean age of 12.8 years. The prevalence of children warranting intervention for low-density lipoprotein cholesterol at baseline was 14%. After 1 year of recommended dietary changes, 51% achieved goal low-density lipoprotein cholesterol, 27% qualified for enhanced dietary and lifestyle modifications, and 22% met criteria for pharmacologic intervention. Elevated triglycerides were more prevalent, with 51% meeting criteria for intervention. At 1 year, 25% achieved goal triglycerides with diet and lifestyle changes, 38% met criteria for advanced dietary modifications, and 37% qualified for antihyperlipidemic medications. CONCLUSIONS:More than one-half of children with NAFLD met intervention thresholds for dyslipidemia. Based on the burden of clinically relevant dyslipidemia, lipid screening in children with NAFLD is warranted. Clinicians caring for children with NAFLD should be familiar with lipid management.

The world’s population is increasingly overweight and obese. According to the World Health Organization (WHO) as of 2010, 43 million children under the age of five were overweight. Once considered to be limited to developed countries, overweight and obese children are now found in low- and middle-income countries, though most commonly in urban areas. Furthermore the WHO now cites the conditions of overweight and obesity as being associated with more deaths around the globe than those associated with being underweight. With this increased prevalence of overweight and obese children has come a host of other medical problems including nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). This review will focus on NAFLD and NASH, their definitions, epidemiology, diagnosis and treatment. The authors will also discuss NAFLD in the Indian subcontinent, and the future of NAFLD and NASH.