Longitudinal Links between Changes in Body Composition and Liver Disease Severity in Children and Adolescents with Metabolic Dysfunction-Associated Steatotic Liver Disease.

OBJECTIVE: To investigate the relationship between longitudinal changes in body composition and liver disease severity in children with metabolic dysfunction-associated steatotic liver disease (MASLD). STUDY DESIGN: This longitudinal, single-center, retrospective analysis included patients aged <20 years followed for MASLD who had had ≥2 bioelectrical impedance analyses (BIAs) performed. MASLD regression was defined as alanine aminotransferase (ALT) normalization or a decrease of >50% from baseline. Fat and skeletal muscle mass were adjusted for size by calculating respective indices (dividing by height2). Logistic and linear regressions were used to determine the independent relationship between changes in body composition over time and serological markers of liver disease severity. RESULTS: We included 258 patients (75% male, 50% Hispanic) with a median age of 14 years (IQR, 11-16 years) at the time of first BIA. Median body mass index (BMI) z-score at baseline was 2.33 (IQR, 2.04-2.62). Median time from first to last BIA was 12 months (IQR, 6-24 months). A decrease in fat mass index was independently associated with reductions in ALT and gamma glutamyl transferase and increased odds of MASLD regression (OR; 0.55; P < .001). Fat mass index reduction was superior to BMI z-score in predicting MASLD regression. Change in skeletal muscle mass index was not associated with change in ALT or gamma glutamyl transferase. CONCLUSIONS: Changes in fat mass, not skeletal muscle mass, are associated with serological markers of liver injury in youth with MASLD. Fat mass changes outperform BMI z-score changes in predicting MASLD regression. BIA can serve as an adjunct biomarker of liver disease progression.

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.

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.

Muscle Mass Is Linked to Liver Disease Severity in Pediatric Nonalcoholic Fatty Liver Disease.

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 <20 years followed from 2009 to 2018. Muscle mass was estimated in all patients by measuring magnetic resonance imaging-based total psoas muscle surface area (tPMSA) and correcting for height (tPMSA index = tPMSA/height2). Two cohorts were studied, one with histological confirmation of NAFLD (n = 100) and the other with magnetic resonance imaging (MRI) evidence of hepatic steatosis (n = 236). Histology was scored using Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) criteria. MRI-measured proton density fat fraction (PDFF) and liver stiffness were collected. Demographic, clinical, and socioeconomic status (using a validated Community Deprivation Index [CDI]) were assessed as covariates. Univariate regression analyses, followed by multivariable regression analyses, were used to determine the relationships between tPMSA index and NAS, MRI-PDFF, and liver stiffness, adjusting for clinical, demographic, and CDI variables. RESULTS: In the multivariable regression analyses, higher steatosis score was associated with a lower tPMSA index (OR, 0.73; 95% CI, 0.56-0.96) and younger age (OR, 0.84; 95% CI, 0.73-0.97). Liver PDFF was also significantly associated with the tPMSA index (P = .029), sex (P = .019), and CDI (P = .005). In contrast, liver stiffness was not associated with tPMSA in multivariable analyses. CONCLUSIONS: tPMSA index was independently associated with both imaging and histological features of hepatic steatosis severity in children. Future studies should directly explore the presence and directionality of causative links between muscle mass and steatosis, as well as whether interventions that enhance muscle mass can reduce disease severity in children with NAFLD.

Glomerular Hyperfiltration Is Associated with Liver Disease Severity in Children with Nonalcoholic Fatty Liver Disease.

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 (<90 mL/min/1.73 m2), normal (90-136 mL/min/1.73 m2), or high (>136 mL/min/1.73 m2). 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.

Assessment of Nonalcoholic Fatty Liver Disease Progression in Children Using Magnetic Resonance Imaging.

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.