{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:23:31Z","timestamp":1787019811522,"version":"build-2736575974"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2010,5,13]],"date-time":"2010-05-13T00:00:00Z","timestamp":1273708800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2010,5,13]],"date-time":"2010-05-13T00:00:00Z","timestamp":1273708800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Genome Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Young age at portoenterostomy has been linked to improved outcome in biliary atresia, but pre-existing biological factors may influence the rate of disease progression. In this study, we aimed to determine whether molecular profiling of the liver identifies stages of disease at diagnosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We examined liver biopsies from 47 infants with biliary atresia enrolled in a prospective observational study. Biopsies were scored for inflammation and fibrosis, used for gene expression profiles, and tested for association with indicators of disease severity, response to surgery, and survival at 2 years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Fourteen of 47 livers displayed predominant histological features of inflammation (N = 9) or fibrosis (N = 5), with the remainder showing similar levels of both simultaneously. By differential profiling of gene expression, the 14 livers had a unique molecular signature containing 150 gene probes. Applying prediction analysis models, the probes classified 29 of the remaining 33 livers into inflammation or fibrosis. Molecular classification into the two groups was validated by the findings of increased hepatic population of lymphocyte subsets or tissue accumulation of matrix substrates. The groups had no association with traditional markers of liver injury or function, response to surgery, or complications of cirrhosis. However, infants with an inflammation signature were younger, while those with a fibrosis signature had decreased transplant-free survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Molecular profiling at diagnosis of biliary atresia uncovers a signature of inflammation or fibrosis in most livers. This signature may relate to staging of disease at diagnosis and has implications to clinical outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/gm154","type":"journal-article","created":{"date-parts":[[2010,5,13]],"date-time":"2010-05-13T15:22:56Z","timestamp":1273764176000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["Staging of biliary atresia at diagnosis by molecular profiling of the liver"],"prefix":"10.1186","volume":"2","author":[{"given":"Katie","family":"Moyer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek","family":"Kaimal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Pacheco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reena","family":"Mourya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pranavkumar","family":"Shivakumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranajit","family":"Chakraborty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marepalli","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C","family":"Magee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Bove","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce J","family":"Aronow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil G","family":"Jegga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge A","family":"Bezerra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2010,5,13]]},"reference":[{"key":"154_CR1","doi-asserted-by":"publisher","first-page":"1682","DOI":"10.1002\/hep.510230652","volume":"23","author":"WF Balistreri","year":"1996","unstructured":"Balistreri WF, Grand R, Hoofnagle JH, Suchy FJ, Ryckman FC, Perlmutter DH, Sokol RJ: Biliary atresia: current concepts and research directions. Summary of a symposium. Hepatology. 1996, 23: 1682-1692. 10.1002\/hep.510230652.","journal-title":"Hepatology"},{"key":"154_CR2","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1055\/s-2007-985068","volume":"27","author":"CL Mack","year":"2007","unstructured":"Mack CL: The pathogenesis of biliary atresia: evidence for a virus-induced autoimmune disease. Semin Liver Dis. 2007, 27: 233-242. 10.1055\/s-2007-985068.","journal-title":"Semin Liver Dis"},{"key":"154_CR3","doi-asserted-by":"publisher","first-page":"1653","DOI":"10.1016\/S0140-6736(02)11603-5","volume":"360","author":"JA Bezerra","year":"2002","unstructured":"Bezerra JA, Tiao G, Ryckman FC, Alonso M, Sabla GE, Shneider B, Sokol RJ, Aronow BJ: Genetic induction of proinflammatory immunity in children with biliary atresia. Lancet. 2002, 360: 1653-1659. 10.1016\/S0140-6736(02)11603-5.","journal-title":"Lancet"},{"key":"154_CR4","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1053\/j.gastro.2007.04.032","volume":"133","author":"CL Mack","year":"2007","unstructured":"Mack CL, Falta MT, Sullivan AK, Karrer F, Sokol RJ, Freed B, Fontenot AP: Oligoclonal expansions of CD4+ and CD8+ T-cells in the target organ of patients with biliary atresia. Gastroenterology. 2007, 133: 278-287. 10.1053\/j.gastro.2007.04.032.","journal-title":"Gastroenterology"},{"key":"154_CR5","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1203\/01.PDR.0000130480.51066.FB","volume":"56","author":"CL Mack","year":"2004","unstructured":"Mack CL, Tucker RM, Sokol RJ, Karrer FM, Kotzin BL, Whitington PF, Miller SD: Biliary atresia is associated with CD4+ Th1 cell-mediated portal tract inflammation. Pediatr Res. 2004, 56: 79-87. 10.1203\/01.PDR.0000130480.51066.FB.","journal-title":"Pediatr Res"},{"key":"154_CR6","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1002\/hep.21366","volume":"44","author":"CL Mack","year":"2006","unstructured":"Mack CL, Tucker RM, Lu BR, Sokol RJ, Fontenot AP, Ueno Y, Gill RG: Cellular and humoral autoimmunity directed at bile duct epithelia in murine biliary atresia. Hepatology. 2006, 44: 1231-1239. 10.1002\/hep.21366.","journal-title":"Hepatology"},{"key":"154_CR7","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1053\/j.gastro.2007.04.031","volume":"133","author":"P Shivakumar","year":"2007","unstructured":"Shivakumar P, Sabla G, Mohanty S, McNeal M, Ward R, Stringer K, Caldwell C, Chougnet C, Bezerra JA: Effector role of neonatal hepatic CD8+ lymphocytes in epithelial injury and autoimmunity in experimental biliary atresia. Gastroenterology. 2007, 133: 268-277. 10.1053\/j.gastro.2007.04.031.","journal-title":"Gastroenterology"},{"key":"154_CR8","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1172\/JCI200421153","volume":"114","author":"P Shivakumar","year":"2004","unstructured":"Shivakumar P, Campbell KM, Sabla GE, Miethke A, Tiao G, McNeal MM, Ward RL, Bezerra JA: Obstruction of extrahepatic bile ducts by lymphocytes is regulated by IFN-gamma in experimental biliary atresia. J Clin Invest. 2004, 114: 322-329.","journal-title":"J Clin Invest"},{"key":"154_CR9","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1055\/s-2008-1071140","volume":"8","author":"C Petersen","year":"1998","unstructured":"Petersen C, Kuske M, Bruns E, Biermanns D, Wussow PV, Mildenberger H: Progress in developing animal models for biliary atresia. Eur J Pediatr Surg. 1998, 8: 137-141. 10.1055\/s-2008-1071140.","journal-title":"Eur J Pediatr Surg"},{"key":"154_CR10","first-page":"394","volume":"33","author":"M Riepenhoff-Talty","year":"1993","unstructured":"Riepenhoff-Talty M, Schaekel K, Clark HF, Mueller W, Uhnoo I, Rossi T, Fisher J, Ogra PL: Group A rotaviruses produce extrahepatic biliary obstruction in orally inoculated newborn mice. Pediatr Res. 1993, 33: 394-399.","journal-title":"Pediatr Res"},{"key":"154_CR11","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1097\/SLA.0b013e3181638627","volume":"247","author":"M Davenport","year":"2008","unstructured":"Davenport M, Caponcelli E, Livesey E, Hadzic N, Howard E: Surgical outcome in biliary atresia: Etiology affects the influence of age at surgery. Ann Surg. 2008, 247: 694-698. 10.1097\/SLA.0b013e3181638627.","journal-title":"Ann Surg"},{"key":"154_CR12","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1016\/S0140-6736(04)16045-5","volume":"363","author":"M Davenport","year":"2004","unstructured":"Davenport M, De Ville de Goyet J, Stringer MD, Mieli-Vergani G, Kelly DA, McClean P, Splitz L: Seamless management of biliary atresia in England and Wales (1999-2002). Lancet. 2004, 363: 1354-1357. 10.1016\/S0140-6736(04)16045-5.","journal-title":"Lancet"},{"key":"154_CR13","doi-asserted-by":"publisher","first-page":"1632","DOI":"10.1002\/hep.21923","volume":"46","author":"PA DeRusso","year":"2007","unstructured":"DeRusso PA, Ye W, Shepherd R, Haber BA, Shneider BL, Whitington PF, Schwarz KB, Bezerra JA, Rosenthal P, Karpen S, Squires RG, Magee JC, Robuck PR, Sokol RJ: Growth failure and outcomes in infants with biliary atresia: a report from the Biliary Atresia Research Consortium. Hepatology. 2007, 46: 1632-1638. 10.1002\/hep.21923.","journal-title":"Hepatology"},{"key":"154_CR14","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1016\/j.jpeds.2007.05.051","volume":"151","author":"RA Schreiber","year":"2007","unstructured":"Schreiber RA, Barker CC, Roberts EA, Martin SR, Alvarez F, Smith L, Butzner JD, Wrobel I, Mack D, Moroz S, Rashid M, Persad R, Levesque D, Brill H, Bruce G, Critch J: Biliary atresia: the Canadian experience. J Pediatr. 2007, 151: 659-665.","journal-title":"J Pediatr"},{"key":"154_CR15","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1002\/hep.21219","volume":"44","author":"MO Serinet","year":"2006","unstructured":"Serinet MO, Broue P, Jacquemin E, Lachaux A, Sarles J, Gottrand F, Gauthier F, Chardot C: Management of patients with biliary atresia in France: results of a decentralized policy 1986-2002. Hepatology. 2006, 44: 75-84. 10.1002\/hep.21219.","journal-title":"Hepatology"},{"key":"154_CR16","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1016\/j.jpeds.2005.12.054","volume":"148","author":"BL Shneider","year":"2006","unstructured":"Shneider BL, Brown MB, Haber B, Whitington PF, Schwarz K, Squires R, Bezerra J, Shepherd R, Rosenthal P, Hoofnagle JH, Sokol RJ: A multicenter study of the outcome of biliary atresia in the United States, 1997 to 2000. J Pediatr. 2006, 148: 467-474. 10.1016\/j.jpeds.2005.12.054.","journal-title":"J Pediatr"},{"key":"154_CR17","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1007\/s003830000573","volume":"17","author":"ET Wu","year":"2001","unstructured":"Wu ET, Chen HL, Ni YH, Lee PI, Hsu HY, Lai HS, Chang MH: Bacterial cholangitis in patients with biliary atresia: impact on short-term outcome. Pediatr Surg Int. 2001, 17: 390-395. 10.1007\/s003830000573.","journal-title":"Pediatr Surg Int"},{"key":"154_CR18","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/S0022-3468(97)90173-1","volume":"32","author":"KS Azarow","year":"1997","unstructured":"Azarow KS, Phillips MJ, Sandler AD, Hagerstrand I, Superina RA: Biliary atresia: should all patients undergo a portoenterostomy?. J Pediatr Surg. 1997, 32: 168-172. 10.1016\/S0022-3468(97)90173-1. discussion 172-164","journal-title":"J Pediatr Surg"},{"key":"154_CR19","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.jpeds.2003.09.042","volume":"144","author":"VS Weerasooriya","year":"2004","unstructured":"Weerasooriya VS, White FV, Shepherd RW: Hepatic fibrosis and survival in biliary atresia. J Pediatr. 2004, 144: 123-125. 10.1016\/j.jpeds.2003.09.042.","journal-title":"J Pediatr"},{"key":"154_CR20","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1002\/lt.21711","volume":"15","author":"L Pape","year":"2009","unstructured":"Pape L, Olsson K, Petersen C, von Wasilewski R, Melter M: Prognostic value of computerized quantification of liver fibrosis in children with biliary atresia. Liver Transpl. 2009, 15: 876-882. 10.1002\/lt.21711.","journal-title":"Liver Transpl"},{"key":"154_CR21","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1002\/lt.21740","volume":"15","author":"PF Whitington","year":"2009","unstructured":"Whitington PF: Fortune telling in biliary atresia: what is in the tea leaves?. Liver Transpl. 2009, 15: 829-830. 10.1002\/lt.21740.","journal-title":"Liver Transpl"},{"key":"154_CR22","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1016\/j.gastro.2005.05.052","volume":"129","author":"E Carvalho","year":"2005","unstructured":"Carvalho E, Liu C, Shivakumar P, Sabla G, Aronow B, Bezerra JA: Analysis of the biliary transcriptome in experimental biliary atresia. Gastroenterology. 2005, 129: 713-717.","journal-title":"Gastroenterology"},{"key":"154_CR23","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1002\/hep.20135","volume":"39","author":"D-Y Zhang","year":"2004","unstructured":"Zhang D-Y, Sabla G, Shivakumar P, Tiao G, Sokol RJ, Mack C, Shneider BL, Aronow BJ, Bezerra JA: Coordinate expression of regulatory genes differentiates embryonic and perinatal forms of biliary atresia. Hepatology. 2004, 39: 954-962. 10.1002\/hep.20135.","journal-title":"Hepatology"},{"key":"154_CR24","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1016\/j.canlet.2006.10.016","volume":"250","author":"A Oberthuer","year":"2007","unstructured":"Oberthuer A, Warnat P, Kahlert Y, Westermann F, Spitz R, Brors B, Hero B, Elis R, Schwab M, Berthold F, Fischer M: Classification of neuroblastoma patients by published gene-expression markers reveals a low sensitivity for unfavorable courses of MYCN non-amplified disease. Cancer Lett. 2007, 250: 250-267. 10.1016\/j.canlet.2006.10.016.","journal-title":"Cancer Lett"},{"key":"154_CR25","doi-asserted-by":"crossref","first-page":"Article37","DOI":"10.2202\/1544-6115.1078","volume":"3","author":"M Ruschhaupt","year":"2004","unstructured":"Ruschhaupt M, Huber W, Poustka A, Mansmann U: A compendium to ensure computational reproducibility in high-dimensional classification tasks. Stat Appl Genet Mol Biol. 2004, 3: Article37-","journal-title":"Stat Appl Genet Mol Biol"},{"key":"154_CR26","doi-asserted-by":"publisher","first-page":"6567","DOI":"10.1073\/pnas.082099299","volume":"99","author":"R Tibshirani","year":"2002","unstructured":"Tibshirani R, Hastie T, Narasimhan B, Chu G: Diagnosis of multiple cancer types by shrunken centroids of gene expression. Proc Natl Acad Sci USA. 2002, 99: 6567-6572. 10.1073\/pnas.082099299.","journal-title":"Proc Natl Acad Sci USA"},{"key":"154_CR27","unstructured":"Genomatix. [http:\/\/www.genomatix.de]"},{"key":"154_CR28","volume-title":"A Handbook of Statistical Analyis Using R","author":"BS Everitt","year":"2005","unstructured":"Everitt BS, Hothorn T: A Handbook of Statistical Analyis Using R. 2005, London: CRC Press"},{"key":"154_CR29","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1016\/j.jpedsurg.2004.12.004","volume":"40","author":"J Feng","year":"2005","unstructured":"Feng J, Li M, Cai T, Tang H, Gu W: Rotavirus-induced murine biliary atresia is mediated by nuclear factor-kappaB. J Pediatr Surg. 2005, 40: 630-636. 10.1016\/j.jpedsurg.2004.12.004.","journal-title":"J Pediatr Surg"},{"key":"154_CR30","first-page":"1189","volume":"55","author":"A Gyorffy","year":"2008","unstructured":"Gyorffy A, Baranyai Z, Cseh A, Munkacsy G, Jakab F, Tulassay Z, Gyorffy B: Promoter analysis suggests the implication of NFkappaB\/C-Rel transcription factors in biliary atresia. Hepatogastroenterology. 2008, 55: 1189-1192.","journal-title":"Hepatogastroenterology"},{"key":"154_CR31","doi-asserted-by":"publisher","first-page":"3135","DOI":"10.1158\/0008-5472.CAN-06-3815","volume":"67","author":"P Corsino","year":"2007","unstructured":"Corsino P, Davis B, Law M, Chytil A, Forrester E, Norgaard P, Teoh N, Law B: Tumors initiated by constitutive Cdk2 activation exhibit transforming growth factor beta resistance and acquire paracrine mitogenic stimulation during progression. Cancer Res. 2007, 67: 3135-3144. 10.1158\/0008-5472.CAN-06-3815.","journal-title":"Cancer Res"},{"key":"154_CR32","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1007\/s11010-006-9286-4","volume":"295","author":"W Guo","year":"2007","unstructured":"Guo W, Xu H, Chen J, Yang Y, Jin JW, Fu R, Liu HM, Zha XL, Zhang ZG, Huang WY: Prohibitin suppresses renal interstitial fibroblasts proliferation and phenotypic change induced by transforming growth factor-beta1. Mol Cell Biochem. 2007, 295: 167-177. 10.1007\/s11010-006-9286-4.","journal-title":"Mol Cell Biochem"},{"key":"154_CR33","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1046\/j.1523-1747.2001.01326.x","volume":"116","author":"F Verrecchia","year":"2001","unstructured":"Verrecchia F, Rossert J, Mauviel A: Blocking sp1 transcription factor broadly inhibits extracellular matrix gene expression in vitro and in vivo: implications for the treatment of tissue fibrosis. J Invest Dermatol. 2001, 116: 755-763. 10.1046\/j.1523-1747.2001.01326.x.","journal-title":"J Invest Dermatol"},{"key":"154_CR34","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.clim.2005.01.012","volume":"115","author":"CL Mack","year":"2005","unstructured":"Mack CL, Tucker RM, Sokol RJ, Kotzin BL: Armed CD4+ Th1 effector cells and activated macrophages participate in bile duct injury in murine biliary atresia. Clin Immunol. 2005, 115: 200-209. 10.1016\/j.clim.2005.01.012.","journal-title":"Clin Immunol"},{"key":"154_CR35","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1111\/j.1399-3046.2008.00947.x","volume":"13","author":"NE Gibelli","year":"2008","unstructured":"Gibelli NE, Tannuri U, de Mello ES, Rodrigues CJ: Bile duct ligation in neonatal rats: Is it a valid experimental model for biliary atresia studies?. Pediatr Transplant. 2008, 13: 81-87. 10.1111\/j.1399-3046.2008.00947.x.","journal-title":"Pediatr Transplant"}],"container-title":["Genome Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/gm154.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/gm154\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/gm154.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T06:12:50Z","timestamp":1728367970000},"score":1,"resource":{"primary":{"URL":"https:\/\/genomemedicine.biomedcentral.com\/articles\/10.1186\/gm154"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,5,13]]},"references-count":35,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2010,5]]}},"alternative-id":["154"],"URL":"https:\/\/doi.org\/10.1186\/gm154","relation":{},"ISSN":["1756-994X"],"issn-type":[{"value":"1756-994X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,5,13]]},"assertion":[{"value":"19 January 2010","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 March 2010","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 May 2010","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 May 2010","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"33"}}