Abstract
BACKGROUND AND AIMS: Detailed investigation of the biological pathways leading to hepatic fibrosis and identification of liver fibrosis biomarkers may facilitate early interventions for pediatric cholestasis. APPROACH AND RESULTS: A 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 < 0.001) and mmp-7 ( p>< 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>< 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. conclusions: endoglin, 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.> 0.0001).> 0.001)> 0.001)>