Paediatric reference values for total psoas muscle area

Background: Sarcopenia, the unintentional loss of skeletal muscle mass, is associated with poor outcomes in adult patient populations. In adults, sarcopenia is often ascertained by cross-sectional imaging of the psoas muscle area (PMA). Although children with chronic medical illnesses may be at increased risk for muscle loss because of nutritional deficiencies, physical deconditioning, endocrine anomalies, and systemic inflammation, consistent quantitative definitions for sarcopenia in children are lacking. We aimed to generate paediatric reference values for PMA at two intervertebral lumbar levels, L3–4 and L4–5. Methods: In this cross-sectional study, we analysed abdominal computed tomography scans of consecutive children presenting to the emergency department. Participants were children 1–16 years who required abdominal cross-sectional imaging after paediatric trauma between January 1, 2005 and December 31, 2015 in a large Canadian quaternary care centre. Children with a documented chronic medical illness or an acute spinal trauma at presentation were excluded. Total PMA (tPMA) at levels L3–4 and L4–5 were measured in square millimetres (mm2) as the sum of left and right PMA. Age-specific and sex-specific tPMA percentile curves were modelled using quantile regression. Results: Computed tomography images from 779 children were included. Values of tPMA at L4–5 were significantly larger than at L3–4 at all ages, but their correlation was high for both girls (r = 0.95) and boys (r = 0.98). Amongst girls, tPMA 50th percentile values ranged from 365 to 2336 mm2 at L3–4 and from 447 to 2704 mm2 for L4–5. Amongst boys, 50th percentile values for tPMA ranged between 394 and 3050 mm2 at L3–4 and from 498 to 3513 mm2 at L4–5. Intraclass correlation coefficients were excellent at L3–4 (0.97, 95% CI 0.94 to 0.981) and L4–5 (0.99, 95% CI 0.986 to 0.995). Weight and tPMA were correlated, stratified by sex for boys (L3–4 r = 0.90; L4–5 r = 0.90) and for girls (L3–4 r = 0.87; L4–5 r = 0.87). An online application was subsequently developed to easily calculate age-specific and sex-specific z-scores and percentiles. Conclusions: We provide novel paediatric age-specific and sex-specific growth curves for tPMA at intervertebral L3–4 and L4–5 levels for children between the ages of 1-16 years. Together with an online tool (https://ahrc-apps.shinyapps.io/sarcopenia/), these tPMA curves should serve as a reference enabling earlier identification and targeted intervention of sarcopenia in children with chronic medical conditions

Early life predictive markers of liver disease outcome in an International, Multicentre Cohort of children with Alagille syndrome

Background & AimsLiver disease in Alagille syndrome is highly variable. Many of the patients presenting with severe cholestasis early in life improve spontaneously; 10-20%, however, have progressive disease. It is currently not possible to predict long-term hepatic outcomes in Alagille syndrome. This international, multicentre study was aimed at identifying early life predictors of liver disease outcome. MethodsRetrospective clinical, laboratory and radiographic data from a cohort of 144 Alagille syndrome patients, whose long-term hepatic outcomes had been determined a priori based on previously published criteria, were collected. ResultsSixty-seven patients had mild and 77 had severe hepatic outcome. Univariate analysis demonstrated that cholestasis and fibrosis on biopsy, as well as the presence of xanthomata were significantly different between the groups (P ConclusionsThe long-term hepatic outcomes of patients with Alagille syndrome can be predicted based on serum total bilirubin between the ages of 12-24months combined with fibrosis on liver biopsy and the presence of xanthomata on physical examination

Frailty in Children with Liver Disease: A Prospective Multicenter Study

Objective To assess frailty, a measure of physiologic declines in multiple organ systems, in children with chronic liver disease using a novel pediatric frailty tool. Study design We performed a prospective cross-sectional multicenter study at 17 liver transplantation (LT) centers. 71 children (5-17 years of age), 36 with compensated chronic liver disease (CCLD) and 35 with end-stage liver disease (ESLD) and listed for LT, were assessed for frailty using validated pediatric tools to assess the 5 classic Fried Frailty Criteria-slowness, weakness, exhaustion, diminished physical activity, and shrinkage. Test scores were translated to age- and sex-dependent z scores, generating a maximum frailty score of 10. Results The median frailty score of the cohort was 4 (IQR 3, 5). Subjects with ESLD had significantly higher frailty scores (median 5; IQR 4, 7) than subjects with CCLD (median 3; IQR 2, 4); (P < .0001). Area under the curve receiver operating characteristic for frailty scores to discriminate between ESLD and CCLD was 0.83 (95% CI 0.73, 0.93). Forty-six percent of children with ESLD were frail and there was no correlation between pediatric frailty scores and physician's global assessments (r = -0.24, 95% CI -0.53, 0.10). Conclusions A novel frailty tool assessed additional dimensions of health, not captured by standard laboratory measures and identified the sickest individuals among a cohort of children with chronic liver disease. This tool may have applicability to other children with chronic disease

Longitudinal Outcomes in Young Patients with Alpha-1-Antitrypsin Deficiency with Native Liver Reveal that Neonatal Cholestasis is a Poor Predictor of Future Portal Hypertension

ObjectivesTo identify predictors of portal hypertension, liver transplantation, and death in North American youth with alpha-1-antitrypsin (AAT) deficiency, and compare with patients with AAT deficiency elsewhere.Study designThe Childhood Liver Disease Research Network Longitudinal Observational Study of Genetic Causes of Intrahepatic Cholestasis is a prospective, cohort study of pediatric cholestatic liver diseases, including AAT deficiency, enrolling PIZZ and PISZ subjects 0-25&nbsp;years of age seen since November 2007 at 17 tertiary care centers in the US and Canada. Data from standard-of-care baseline and annual follow-up visits were recorded from medical records, history, physical examination, and laboratory studies. Participants with portal hypertension were identified based on data collected.ResultsWe enrolled 350 participants (60% male) with a native liver; 278 (79%) entered the cohort without portal hypertension and 18 developed portal hypertension during follow-up. Thirty participants required liver transplantation; 2 patients died during 1077 person-years of follow-up. There was no difference in participants with or without preceding neonatal cholestasis progressing to transplantation or death during the study (12% vs 7%; P&nbsp;=&nbsp;.09), or in experiencing portal hypertension (28% vs 21%; P&nbsp;=&nbsp;.16); the hazard ratio for neonatal cholestasis leading to portal hypertension was P&nbsp;=&nbsp;.04. Development of portal hypertension was associated with a reduced height Z-score.ConclusionsPortal hypertension in youth with AAT deficiency impacts growth measures. Progression to liver transplantation is slow and death is rare, but the risk of complications and severe liver disease progression persists throughout childhood. A&nbsp;history of neonatal cholestasis is a weak predictor of severe disease

Serum biomarkers correlated with liver stiffness assessed in a multicenter study of pediatric cholestatic liver disease

Background and aimsDetailed investigation of the biological pathways leading to hepatic fibrosis and identification of liver fibrosis biomarkers may facilitate early interventions for pediatric cholestasis.Approach and resultsA targeted enzyme-linked immunosorbent assay-based panel of nine biomarkers (lysyl oxidase, tissue inhibitor matrix metalloproteinase (MMP) 1, connective tissue growth factor [CTGF], IL-8, endoglin, periostin, Mac-2-binding protein, MMP-3, and MMP-7) was examined in children with biliary atresia (BA; n = 187), alpha-1 antitrypsin deficiency (A1AT; n = 78), and Alagille syndrome (ALGS; n = 65) and correlated with liver stiffness (LSM) and biochemical measures of liver disease. Median age and LSM were 9 years and 9.5 kPa. After adjusting for covariates, there were positive correlations among LSM and endoglin ( p = 0.04) and IL-8 ( p &lt; 0.001) and MMP-7 ( p &lt; 0.001) in participants with BA. The best prediction model for LSM in BA using clinical and lab measurements had an R2 = 0.437; adding IL-8 and MMP-7 improved R2 to 0.523 and 0.526 (both p &lt; 0.0001). In participants with A1AT, CTGF and LSM were negatively correlated ( p = 0.004); adding CTGF to an LSM prediction model improved R2 from 0.524 to 0.577 ( p = 0.0033). Biomarkers did not correlate with LSM in ALGS. A significant number of biomarker/lab correlations were found in participants with BA but not those with A1AT or ALGS.ConclusionsEndoglin, IL-8, and MMP-7 significantly correlate with increased LSM in children with BA, whereas CTGF inversely correlates with LSM in participants with A1AT; these biomarkers appear to enhance prediction of LSM beyond clinical tests. Future disease-specific investigations of change in these biomarkers over time and as predictors of clinical outcomes will be important