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

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 R 2 = 0.437; adding IL‐8 and MMP‐7 improved R 2 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 R 2 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.