Serum biomarkers correlated with liver stiffness assessed in a multicenter study of pediatric cholestatic liver disease.
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Leung Daniel H, Devaraj Sridevi, Goodrich Nathan P, Chen Xinpu, Rajapakshe Deepthi, Ye Wen, Andreev Victor, Minard Charles G, Guffey Danielle, Molleston Jean P, Bass Lee M, Karpen Saul J, Kamath Binita M, Wang Kasper S, Sundaram Shikha S, Rosenthal Philip, McKiernan Patrick, Loomes Kathleen M, Jensen M Kyle, Horslen Simon P, Bezerra Jorge A, Magee John C, Merion Robert M, Sokol Ronald J, Shneider Benjamin L, Alonso Estella, Bass Lee, Kelly Susan, Riordan Mary, Melin-Aldana Hector, Bezerra Jorge, Bove Kevin, Heubi James, Miethke Alexander, Tiao Greg, Denlinger Julie, Chapman Erin, Sokol Ronald, Feldman Amy, Mack Cara, Narkewicz Michael, Suchy Frederick, Sundaram Shikha S, Van Hove Johan, Garcia Benigno, Kauma Mikaela, Kocher Kendra, Steinbeiss Matthew, Lovell Mark, Loomes Kathleen M, Piccoli David, Rand Elizabeth, Russo Pierre, Spinner Nancy, Erlichman Jessi, Stalford Samantha, Pakstis Dina, King Sakya, Squires Robert, Sindhi Rakesh, Venkat Veena, Bukauskas Kathy, McKiernan Patrick, Haberstroh Lori, Squires James, Rosenthal Philip, Bull Laura, Curry Joanna, Langlois Camille, Kim Grace, Teckman Jeffery, Kociela Vikki, Nagy Rosemary, Patel Shraddha, Cerkoski Jacqueline, Molleston Jean P, Bozic Molly, Subbarao Girish, Klipsch Ann, Sawyers Cindy, Cummings Oscar, Horslen Simon P, Murray Karen, Hsu Evelyn, Cooper Kara, Young Melissa, Finn Laura, Kamath Binita M, Ng Vicky, Quammie Claudia, Putra Juan, Sharma Deepika, Parmar Aishwarya, Guthery Stephen, Jensen Kyle, Rutherford Ann, Lowichik Amy, Book Linda, Meyers Rebecka, Hall Tyler, Wang Kasper S, Michail Sonia, Thomas Danny, Goodhue Catherine, Kohli Rohit, Wang Larry, Soufi Nisreen, Thomas Daniel, Karpen Saul, Gupta Nitika, Romero Rene, Vos Miriam B, Tory Rita, Berauer John-Paul, Abramowsky Carlos, McFall Jeanette, Shneider Benjamin L, Harpavat Sanjiv, Hertel Paula, Leung Daniel, Tessier Mary, Schady Deborah, Cavallo Laurel, Olvera Diego, Banks Christina, Tsai Cynthia, Thompson Richard, Doo Edward, Hoofnagle Jay, Sherker Averell, Torrance Rebecca, Hall Sherry, Magee John, Merion Robert, Spino Cathie, Ye Wen, Childhood Liver Disease Research Network
Аннотация
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.