SAFETY study: alanine aminotransferase cutoff values are set too high for reliable detection of pediatric chronic liver disease.

BACKGROUND & AIMS: The appropriate alanine aminotransferase (ALT) threshold value to use for diagnosis of chronic liver disease in children is unknown. We sought to develop gender-specific, biology-based, pediatric ALT thresholds. METHODS: The Screening ALT for Elevation in Today's Youth (SAFETY) study collected observational data from acute care children's hospitals, the National Health and Nutrition Examination Survey (NHANES, 1999-2006), overweight children with and without non-alcoholic fatty liver disease (NAFLD), and children with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections. The study compared the sensitivity and specificity of ALT thresholds currently used by children's hospitals vs study-derived, gender-specific, biology-based, ALT thresholds for detecting children with NAFLD, HCV, or HBV. RESULTS: The median upper limit of ALT at children's hospitals was 53 U/L (range, 30-90 U/L). The 95th percentile levels for ALT in healthy weight, metabolically normal, liver disease-free, NHANES pediatric participants were 25.8 U/L (boys) and 22.1 U/L (girls). The concordance statistics of these NHANES-derived thresholds for liver disease detection were 0.85 (95% confidence interval [CI]: 0.74-0.96) in boys and 0.91 (95% CI: 0.83-0.99) in girls for NAFLD, 0.80 (95% CI: 0.70-0.91) in boys and 0.79 (95% CI: 0.69-0.89) in girls for HBV, and 0.86 (95% CI: 0.77-0.95) in boys and 0.84 (95% CI: 0.75-0.93) in girls for HCV. Using current children's hospitals ALT thresholds, the median sensitivity for detection of NAFLD, HBV, and HCV ranged from 32% to 48%; median specificity was 92% (boys) and 96% (girls). Using NHANES-derived thresholds, the sensitivities were 72% (boys) and 82% (girls); specificities were 79% (boys) and 85% (girls). CONCLUSIONS: The upper limit of ALT used in children's hospitals varies widely and is set too high to reliably detect chronic liver disease. Biology-based thresholds provide higher sensitivity and only slightly less specificity. Clinical guidelines for use of screening ALT and exclusion criteria for clinical trials should be modified.

Cardiovascular risk factors and the metabolic syndrome in pediatric nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD), the most common cause of liver disease in children, is associated with obesity and insulin resistance. However, the relationship between NAFLD and cardiovascular risk factors in children is not fully understood. The objective of this study was to determine the association between NAFLD and the presence of metabolic syndrome in overweight and obese children. METHODS AND RESULTS: This case-control study of 150 overweight children with biopsy-proven NAFLD and 150 overweight children without NAFLD compared rates of metabolic syndrome using Adult Treatment Panel III criteria. Cases and controls were well matched in age, sex, and severity of obesity. Children with NAFLD had significantly higher fasting glucose, insulin, total cholesterol, low-density lipoprotein cholesterol, triglycerides, systolic blood pressure, and diastolic blood pressure than overweight and obese children without NAFLD. Subjects with NAFLD also had significantly lower high-density lipoprotein cholesterol than controls. After adjustment for age, sex, race, ethnicity, body mass index, and hyperinsulinemia, children with metabolic syndrome had 5.0 (95% confidence interval, 2.6 to 9.7) times the odds of having NAFLD as overweight and obese children without metabolic syndrome. CONCLUSIONS: NAFLD in overweight and obese children is strongly associated with multiple cardiovascular risk factors. The identification of NAFLD in a child should prompt global counseling to address nutrition, physical activity, and avoidance of smoking to prevent the development of cardiovascular disease and type 2 diabetes.

Television viewing and hypertension in obese children.

BACKGROUND: Television viewing is strongly associated with an increased risk of childhood and adolescent obesity. However, the association between TV viewing and hypertension in children is unknown. This study aimed to identify whether TV watching is associated with hypertension in obese children. METHODS: Children seen for obesity, aged 4 to 17 years, were evaluated at three pediatric centers from 2003 to 2005. In 2006-2007, a logistic regression model estimated the odds of hypertension for hours of daily TV time controlling for race, site, and body mass index (BMI) z-score. RESULTS: A total of 546 subjects, with a mean age of 12 years, were evaluated. The children had a mean BMI of 35.5+/-9.3 kg/m(2) (98.7th+/-0.8 percentile, z-score 2.54+/-0.4). TV time was positively correlated with the severity of obesity. After controlling for race, site, and BMI z-score, both the severity of obesity and daily TV time were significant independent predictors of the presence of hypertension. Children watching 2 to 4 hours of TV had 2.5 times the odds of hypertension compared with children watching 0 to <2 hours. The odds of hypertension for children watching 4 or more hours of TV were 3.3 times greater than for children watching 0 to <2 hours of TV. CONCLUSIONS: In obese children, the amount of time spent watching TV is associated with both hypertension and the severity of obesity. Thus, TV viewing is a potential target for addressing hypertension in obese children.

Health-related quality of life in pediatric patients with irritable bowel syndrome: a comparative analysis.

The primary aim of the study was to investigate the generic health-related quality of life (HRQOL) of pediatric patients meeting Rome II criteria for irritable bowel syndrome (IBS) in comparison to healthy children. The secondary aim was to compare pediatric patients with IBS to pediatric patients with Rome II criteria diagnosed functional abdominal pain (FAP) and patients with diagnosed organic gastrointestinal (GI) disorders. The study also investigated the associations between GI symptoms with generic HRQOL and evaluated group differences in school days missed and days sick in bed and needing care. HRQOL was measured with the PedsQLtrade mark 4.0 Generic Core Scales (Physical, Emotional, Social, and School Functioning). The PedsQLtrade mark was administered in outpatient pediatric gastroenterology clinics in California, Texas, and New Jersey. A total of 287 families (280 child self-report, 286 parent proxy-report) with children diagnosed with IBS (n = 123), FAP (n = 82), or organic GI disorders (n = 82) participated. Pediatric patients with IBS demonstrated significantly lower Physical, Emotional, Social, and School Functioning in comparison to healthy children, and comparable HRQOL to patients with FAP and organic GI diagnoses. GI symptoms were significantly associated with generic HRQOL. Patients with IBS demonstrated a significantly greater number of days missed from school, days sick in bed/too ill to play, and days needing someone to care for them than healthy children, but significantly fewer days than patients with FAP and organic GI disorders. Pediatric patients with IBS demonstrated impaired HRQOL in dimensions measuring Physical, Emotional, Social, and School Functioning. These findings suggest the need for targeted interventions to address these dimensions of impaired HRQOL.

Diagnosis and treatment of pediatric nonalcoholic steatohepatitis and the implications for bariatric surgery.

This review focuses on the diagnosis, risk factors, prevalence, pathogenesis and treatment of pediatric nonalcoholic steatohepatitis (NASH). NASH is a progressive form of nonalcoholic fatty liver disease (NAFLD), the most common cause of chronic liver disease in children. The factors that account for differences between children with NASH and children with milder forms of NAFLD are unclear. The diagnosis of NASH requires interpretation of liver histology because no noninvasive markers predict the presence or severity of NASH. There is no proven treatment for NASH. Several clinical trials for NAFLD are in progress; however, clinical trials focusing on NASH are needed. Heightened physician awareness of NAFLD, NASH, and associated risk factors is important to identify and treat affected children.

Musculoskeletal pain in obese children and adolescents.

AIM: To determine whether bodyweight is associated with musculoskeletal pain within a population of obese children and adolescents. METHODS: A descriptive, cross-sectional study of subjects evaluated at a tertiary care medical centre for the management of obesity. Analyses were conducted using both a person-specific model, and then again, using a joint site model in order to account for correlations between joints within children. RESULTS: We evaluated 135 children and adolescents (68 girls, 67 boys) with a mean age of 12.3 years (range: 3-18). The study population was racially and ethnically diverse--Hispanic (51%), non-Hispanic white (26%), non-Hispanic black (13%), other (10%). The majority of subjects (61%) complained of at least one joint hurting more than once per month. Back pain was the most common complaint (39%), followed by foot (26%) and knee (24%) pain. After adjustment for age, pain in the knees and hips were associated with increased weight and/or body mass index (BMI). CONCLUSIONS: In this cross-sectional analysis of obese children and adolescents, musculoskeletal pain was common and, in the knee and hip joints, was positively associated with extra bodyweight. Clinicians may want to ask about musculoskeletal pain when recommending physical activity for weight management counselling.