Liberal Fluid Resuscitation is Associated with Improved Outcomes in Pediatric Acute Pancreatitis.

OBJECTIVE: To evaluate outcomes of children from an observational cohort registry of index acute pancreatitis (AP) admissions managed with different types and rates of intravenous fluid therapy. STUDY DESIGN: Patients with index admission of AP between 2013 and 2023 were included. Those who received >1.5x the maintenance intravenous fluid rate were assigned to the liberal fluid group, and patients who received <1.5x maintenance fluids were assigned to the conservative group. Outcomes including intensive care unit admission rate, organ dysfunction, local pancreatic complications, and AP severity were evaluated. Influence of early enteral feeding and fluid composition on outcomes and clinical course were also analyzed. RESULTS: Patients who received liberal fluids were less likely to be admitted or transferred to the intensive care unit compared with those receiving conservative management (OR, 0.32; 95% CI, 0.12-0.80; P = .015). The liberal fluid group with early feeding had the lowest rate of moderate/severe manifestations of AP compared with other combinations of diet and fluid orders. Patients within the liberal fluid group who received the highest fluid rates (>2x maintenance) did not have higher rates of organ dysfunction or severe disease. CONCLUSIONS: Children with AP may stand to benefit from liberal fluid therapy and continued diet compared with more conservative fluid resuscitation and nothing by mouth status.

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.

Racial Disparities in Pediatric Inflammatory Bowel Disease Care: Differences in Outcomes and Health Service Utilization Between Black and White Children.

OBJECTIVE: To describe racial inequities in pediatric inflammatory bowel disease care and explore potential drivers. METHODS: We undertook a single-center, comparative cohort study of newly diagnosed Black and non-Hispanic White patients with inflammatory bowel disease, aged <21 years, from January 2013 through 2020. Primary outcome was corticosteroid-free remission (CSFR) at 1 year. Other longitudinal outcomes included sustained CSFR, time to anti-tumor necrosis factor therapy, and evaluation of health service utilization. RESULTS: Among 519 children (89% White, 11% Black), 73% presented with Crohn's disease and 27% with ulcerative colitis. Disease phenotype did not differ by race. More patients from Black families had public insurance (58% vs 30%, P < .001). Black patients were less likely to achieve CSFR 1-year post diagnosis (OR: 0.52, 95% CI:0.3-0.9) and less likely to achieve sustained CSFR (OR: 0.48, 95% CI: 0.25-0.92). When adjusted by insurance type, differences by race to 1-year CSFR were no longer significant (aOR: 0.58; 95% CI: 0.33, 1.04; P = .07). Black patients were more likely to transition from remission to a worsened state, and less likely to transition to remission. We found no differences in biologic therapy utilization or surgical outcomes by race. Black patients had fewer gastroenterology clinic visits and 2-fold increased odds for emergency department visits. CONCLUSIONS: We observed no differences by race in phenotypic presentation and medication usage. Black patients had half the odds of achieving clinical remission, but a degree of this was mediated by insurance status. Understanding the cause of such differences will require further exploration of social determinants of health.

Recent Increase in Incidence of Severe Acute Hepatitis of Unknown Etiology in Children is Associated with Infection with Adenovirus and Other Nonhepatotropic Viruses.

OBJECTIVE: To evaluate whether the nature and severity of non-A-E severe acute hepatitis in children noted by the World Health Organization from late 2021 through early 2022 was indeed increased in 2021-2022 compared with prior years. STUDY DESIGN: We performed a single-center, retrospective study to track the etiology and outcomes of children with non-A-E severe acute hepatitis in 2021-2022 compared with the prior 3-year periods (2018-2019, 2019-2020, and 2020-2021). We queried electronic medical records of children ≤16 years of age with alanine or aspartate aminotransferase levels of >500 IU. Data were analyzed for the periods of October 1, 2021, to May 1, 2022, and compared with the same time periods in 2018-2021. RESULTS: Of 107 children meeting entry criteria, 82 cases occurred from October to May of 2018-2022. The average annual case number was 16.3 in 2018-2021 compared with a 2-fold increase (to 33) in 2021-2022 (P = .0054). Analyses of etiologies showed that this increase was associated with a higher number of children who tested positive for viruses (n = 16) when compared with the average of 3.7 for 2018-2021 (P = .018). Adenovirus (26.1%) and severe acute respiratory syndrome coronavirus-2 (10.3%) were the most frequently detected viruses in 2021-2022. Despite evidence of acute liver failure in 37.8% of children in the entire cohort and in 47% of those with viral infection, the overall survival rate was high at 91.4% and 88.9%, respectively. CONCLUSIONS: The number of children with severe acute hepatitis in our center increased from 2021 to May 2022, with a greater frequency of cases associated with adenovirus, yet transplant-free survival remains high.

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.

Relative Risk Analysis of Liver-related Adverse Drug Reactions in Children Based on China's National Spontaneous Reporting System.

OBJECTIVE: To compare the risk of liver-related adverse drug reactions (ADRs) in children and adults. STUDY DESIGN: A case/non-case analysis on spontaneous reports based on the China National Adverse Drug Reactions Monitoring System database were conducted, focusing on events of liver-related ADRs in children younger than 14 years of age. Both the relative risk of liver-related ADRs in children vs entire population and the risk stratification in children were expressed as a measure of disproportionality using the reporting odds ratio (ROR). RESULTS: There were 1206 cases of pediatric liver-related ADRs identified from 2012 to 2016, accounting for 2.82% of the entire population. The greatest ROR values in children from 0 to 14 years vs the entire population were observed for analgesics (3.97, 95% CI 3.27-4.81), respiratory (2.60, 95% CI 1.04-6.43), antineoplastic (2.29, 95% CI 2.02-2.58), immunomodulatory (1.91, 95% CI 1.44-2.53), and antimicrobial agents (1.47, 95% CI 1.33-1.63). Notably, infants aged 0-1 years showed significantly greater risk (3.14, 95% CI 2.85-3.48) of liver-related ADRs than the other age groups of children. For infants, analgesics (3.21, 95% CI 2.20-4.66) and antimicrobials (3.15, 95% CI 2.50-3.97) agents were found to have the greatest adjusted RORs than other drug categories. The highest RORs were found for meropenem, amoxicillin, fluconazole, vancomycin, cefaclor, and ceftazidime in the antimicrobial agents for infants. CONCLUSIONS: Children are sensitive to liver-related ADRs caused by several specific drug categories, and infants are the most sensitive.

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.

Sensitivity of Biochemical and Imaging Findings for the Diagnosis of Acute Pancreatitis in Children.

OBJECTIVE: To determine the diagnostic sensitivity of serum biomarkers and imaging in the diagnosis of acute pancreatitis in children. STUDY DESIGN: This was a cross-sectional analysis of prospective registry data for children (age <21 years) whose first documented attack of acute pancreatitis occurred between March 2013 and October 2016 at a single-institution, tertiary care center. Main outcome was sensitivity of serum biomarkers and of imaging modalities, measured via descriptive statistics. RESULTS: In total, 112 children met the criteria for acute pancreatitis; 57 (51%) were male with a median age of 13.4 years (IQR 9.3-15.8 years). Serum amylase and lipase levels were obtained in 85 (76%) and 112 (100%) patients, respectively. Imaging was performed in 98 (88%) patients, with abdominal ultrasound (US) performed in 84 (75%) and computed tomography and/or magnetic resonance imaging performed in 46 (41%) patients. Fifty-three (47%) patients met all 3 diagnostic criteria (clinical, biochemical, and imaging) for acute pancreatitis. Laboratory testing had a 5.4% false-negative rate for acute pancreatitis. Serum lipase alone and amylase alone were 95% (95% CI 89%-98%) and 39% (95% CI 28%-50%) sensitive for acute pancreatitis, respectively. Imaging (any modality) was 61% sensitive (95% CI 51%-71%) for acute pancreatitis with a 34% false-negative rate. US alone was 52% (95% CI 41%-63%) sensitive for acute pancreatitis and computed tomography/magnetic resonance imaging was 78% (95% CI 63%-89%) sensitive. Combinations of diagnostic criteria performed no better than laboratory testing alone. CONCLUSIONS: The majority of children coming to medical attention with their first documented occurrence of acute pancreatitis have characteristic symptoms. Serum lipase is highly sensitive for the diagnosis of acute pancreatitis, and serum amylase is moderately sensitive. Imaging, particularly US, is only moderately sensitive, and cross-sectional imaging provides greater sensitivity for diagnosing acute pancreatitis.

Early Enteral Nutrition and Aggressive Fluid Resuscitation are Associated with Improved Clinical Outcomes in Acute Pancreatitis.

OBJECTIVES: To determine whether recommendations for treatment of acute pancreatitis (AP) in adults impact the outcomes of pediatric AP. STUDY DESIGN: Adult guidelines regarding early management of AP were implemented through an admission order set at Cincinnati Children's Hospital Medical Center at the beginning of the year 2014. Recommendations included administering high rates of intravenous fluid (IVF) within 24 hours of admission and enteral nutrition within 48 hours of admission. A retrospective chart review of AP admissions before and after the implementation of the recommendations was undertaken. Outcomes studied were: hospital length of stay, intensive care unit transfer rates, development of severe AP, pulmonary complications, and readmission rates post discharge from the hospital. RESULTS: The study included 201 patients. Children who received feeds within the first 48 hours and received greater than maintenance IVF within 24 hours had a shorter length of stay, less intensive care unit admissions and severe AP rates compared with the patients who remained nil per os during the first 48 hours and received lower rates of IVF. CONCLUSION: Our data support that early enteral nutrition and early aggressive IVF improve outcomes of pediatric AP.