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Daniel H. Leung, M.D., FAASLD, FAAP, Associate Professor of Pediatrics, Director, Hepatology and Liver Transplant Medicine, Baylor College of Medicine and Texas Children’s Hospital, Pediatric Gastroenterology, Hepatology and Nutrition, 6701 Fannin St., CCT 1010.00, Houston, TX 77030, 832-822-3606. Email: dhleung@texaschildrens.org

1) Substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; DHL, SD, NPG, XC, DR, WY, VA, CGM, DG, JCM, RMM, RJS, BLS 2) Drafting the article or revising it critically for important intellectual content; DHL, SD, NPG, WY, VA, CGM, DG, JPM, LMB, SJK, BMK, KSW, SSS, PR, PM, KML, MKJ, SH, JAB, JCM, RMM, RJS, BLS 3) Final approval of the version to be published; DHL, SD, NPG, XC, DR, WY, VA, CGM, DG, JPM, LMB, SJK, BMK, KSW, SSS, PR, PM, KML, MKJ, SH, JAB, JCM, RMM, RJS, BLS

Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL (supported by NIDDK DK62436 and NCATS UL1TR001422): Estella Alonso, MD; Lee Bass, MD; Susan Kelly, RN, BSN; Mary Riordan, CCRP; Hector Melin-Aldana, MD Cincinnati Children’s Hospital Medical Center, Cincinnati, OH (supported by NIDDK DK62497 and NCATS UL1TR000077): Jorge Bezerra, MD; Kevin Bove, MD; James Heubi, MD; Alexander Miethke, MD; Greg Tiao, MD; Julie Denlinger, BSN, RN; Erin Chapman Children’s Hospital Colorado, Aurora, CO (supported by NIDDK DK62453 and NCATS UL1TR001082): Ronald Sokol, MD; Amy Feldman, MD; Cara Mack, MD; Michael Narkewicz, MD; Frederick Suchy, MD; Shikha Sundaram, MD; Johan Van Hove, MD; Benigno Garcia; Mikaela Kauma; Kendra Kocher, CCRP; Matthew Steinbeiss, MS, CCRP; Mark Lovell, MD The Children’s Hospital of Philadelphia, Philadelphia, PA (supported by NIDDK DK62481 ): Kathleen Loomes, MD; David Piccoli, MD; Elizabeth Rand, MD; Pierre Russo, MD; Nancy Spinner, PhD; Jessi Erlichman, MPH; Samantha Stalford, MPH; Dina Pakstis; Sakya King Children’s Hospital of Pittsburgh, Pittsburgh, PA (supported by NIDDK DK62466 and NCATS UL1TR000005): Robert Squires, MD; Rakesh Sindhi, MD; Veena Venkat, MD; Kathy Bukauskas, RN, CCRC; Patrick McKiernan, MD; Lori Haberstroh, RN, BSN; James Squires, MD, MS UCSF Children’s Hospital, San Francisco, CA (supported by NIDDK DK62500 and NCATS UL1TR000004): Philip Rosenthal, MD; Laura Bull, PhD; Joanna Curry; Camille Langlois, MS; Grace Kim, MD Saint Louis University School of Medicine, St. Louis, MO (supported by NIDDK DK62453): Jeffery Teckman, MD; Vikki Kociela, BSN, CCRC; Rosemary Nagy, RDN, MBA; Shraddha Patel, PhD; Jacqueline Cerkoski, BSN Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN (supported by NIDDK DK84536 and NCATS UL1TR001108): Jean P. Molleston, MD; Molly Bozic, MD; Girish Subbarao, MD; Ann Klipsch, RN; Cindy Sawyers, BSRT; Oscar Cummings, MD Seattle Children’s Hospital, Seattle WA (supported by NIDDK DK84575 and NCATS UL1TR000423): Simon Horslen, MB, ChB, FRCPCH; Karen Murray, MD; Evelyn Hsu, MD; Kara Cooper, CCRC; Melissa Young, CCRC; Laura Finn, MD The Hospital for Sick Children, Toronto, Ontario, CANADA (supported by NIDDK DK103135): Binita Kamath, MD; Vicky Ng, MD; Claudia Quammie, CCRP; Juan Putra, MD; Deepika Sharma, MSc; Aishwarya Parmar, BSc University of Utah, Salt Lake City, UT (supported by NIDDK DK103140): Stephen Guthery, MD; Kyle Jensen, MD; Ann Rutherford; Amy Lowichik, MD, PhD; Linda Book, MD; Rebecka Meyers, MD; Tyler Hall Children’s Hospital Los Angeles, Los Angeles, CA (supported by NIDDK DK84538 and NCATS UL1TR000130): Kasper Wang, MD; Sonia Michail, MD; Danny Thomas, MD; Catherine Goodhue, CPNP; Rohit Kohli, MBBS, MS; Larry Wang, MD, PhD; Nisreen Soufi, MD; Daniel Thomas, MD Children’s Healthcare of Atlanta, Atlanta, GA (supported by NIDDK DK062470 and NCATS UL1TR000454): Saul Karpen, MD, PhD; Nitika Gupta, MD, DCH, DNB, MRCPH; Rene Romero, Jr., MD; Miriam B. Vos, MD, MSPH; Rita Tory, MS, CCRP; John-Paul Berauer, MD; Carlos Abramowsky, MD; Jeanette McFall, MPH Texas Children’s Hospital, Houston, TX (supported by NIDDK DK103149): Benjamin Shneider, MD; Sanjiv Harpavat, MD; Paula Hertel, MD; Daniel Leung, MD; Mary Tessier, MD; Deborah Schady, MD; Laurel Cavallo; Diego Olvera; Christina Banks; Cynthia Tsai King’s College Hospital, London, UK: Richard Thompson, BM, BCh, MRCP, MRCPCH National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD: Edward Doo, MD; Jay Hoofnagle, MD; Averell Sherker, MD, FRCP; Rebecca Torrance, RN, MSN; Sherry Hall, MS Scientific Data Coordinating Center, Ann Arbor, MI (supported by NIDDK DK62456): John Magee, MD; Robert Merion, MD, FACS; Cathie Spino, DSc; Wen Ye, PhD Financial Support This work was supported by U01 grants from the National Institute of Diabetes, Digestive and Kidney Diseases (DK 62445 [Mt. Sinai School of Medicine], DK 62497 [Cincinnati Children’s Hospital Medical Center], DK 62470 [Children’s Healthcare of Atlanta], DK 62481 [The Children’s Hospital of Philadelphia], DK 62456 [The University of Michigan], DK 84536 [Riley Hospital for Children], DK 84575 [Seattle Children’s Hospital], DK 62500 [UCSF Children’s Hospital], DK 62466 [Children’s Hospital of Pittsburgh of UPMC], DK 62453 [Children’s Hospital Colorado], DK 84538 [Children’s Hospital Los Angeles], DK 62436 [Ann & Robert H Lurie Children’s Hospital of Chicago], DK103149 [Texas Children’s Hospital], DK103135 [The Hospital for Sick Children], DK103140 [University of Utah]). In addition, the project described was supported by National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (NCATS CTSA) grants: University of Colorado UL1 TR002535, UCSF Children’s Hospital UL1 TR001872, Children’s Hospital of Pittsburgh of UPMC UL1 TR001857, The Children’s Hospital of Philadelphia UL1 TR001878, Seattle Children’s Hospital UL1 TR000423 and UL1 RR025014, Children’s Healthcare of Atlanta UL1TR002378, Children’s Hospital of Los Angeles UL1TR00130.

DHL receives grant/research support from Abbvie, Gilead, and Mirum and has served as medical advisor for Merck, Gilead and Vertex. JPM receives grant/research support from Abbvie, Albireo, Mirum, Gilead. KML is a consultant for Mirum, Albireo and Travere Therapeutics and receives grant/research support from Mirum and Albireo. BMK is a Consultant for Mirum, Albireo, Third Rock Ventures and Audentes, BMK receives unrestricted educational funding from Mirum and Albireo. PR receives grant/research support from Abbvie, Albireo, Arrowhead, Gilead, Merck, Mirum, Takeda/Vertex, Travere and has served as a consultant for Albireo, Ambys, Audentes, BioMarin, Dicerna, Encoded, Gilead, MedinCell, Mirum, Takeda/Vertex, Travere.



  • Science & Technology
  • Life Sciences & Biomedicine
  • Gastroenterology & Hepatology

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

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Journal Title:



Volume 77, Number 2


, Pages 530-545

Type of Work:

Article | Post-print: After Peer Review


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.
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