{Reference Type}: Multicenter Study
{Title}: Serum biomarkers correlated with liver stiffness assessed in a multicenter study of pediatric cholestatic liver disease.
{Author}: Leung DH;Devaraj S;Goodrich NP;Chen X;Rajapakshe D;Ye W;Andreev V;Minard CG;Guffey D;Molleston JP;Bass LM;Karpen SJ;Kamath BM;Wang KS;Sundaram SS;Rosenthal P;McKiernan P;Loomes KM;Jensen MK;Horslen SP;Bezerra JA;Magee JC;Merion RM;Sokol RJ;Shneider BL;Alonso E;Bass L;Kelly S;Riordan M;Melin-Aldana H;Bezerra J;Bove K;Heubi J;Miethke A;Tiao G;Denlinger J;Chapman E;Sokol R;Feldman A;Mack C;Narkewicz M;Suchy F;Sundaram SS;Van Hove J;Garcia B;Kauma M;Kocher K;Steinbeiss M;Lovell M;Loomes KM;Piccoli D;Rand E;Russo P;Spinner N;Erlichman J;Stalford S;Pakstis D;King S;Squires R;Sindhi R;Venkat V;Bukauskas K;McKiernan P;Haberstroh L;Squires J;Rosenthal P;Bull L;Curry J;Langlois C;Kim G;Teckman J;Kociela V;Nagy R;Patel S;Cerkoski J;Molleston JP;Bozic M;Subbarao G;Klipsch A;Sawyers C;Cummings O;Horslen SP;Murray K;Hsu E;Cooper K;Young M;Finn L;Kamath BM;Ng V;Quammie C;Putra J;Sharma D;Parmar A;Guthery S;Jensen K;Rutherford A;Lowichik A;Book L;Meyers R;Hall T;Wang KS;Michail S;Thomas D;Goodhue C;Kohli R;Wang L;Soufi N;Thomas D;Karpen S;Gupta N;Romero R;Vos MB;Tory R;Berauer JP;Abramowsky C;McFall J;Shneider BL;Harpavat S;Hertel P;Leung D;Tessier M;Schady D;Cavallo L;Olvera D;Banks C;Tsai C;Thompson R;Doo E;Hoofnagle J;Sherker A;Torrance R;Hall S;Magee J;Merion R;Spino C;Ye W; ;
{Journal}: Hepatology
{Volume}: 77
{Issue}: 2
{Year}: 02 2023 1
{Factor}: 17.298
{DOI}: 10.1002/hep.32777
{Abstract}: Detailed investigation of the biological pathways leading to hepatic fibrosis and identification of liver fibrosis biomarkers may facilitate early interventions for pediatric cholestasis.
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.
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.