{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T11:19:36Z","timestamp":1761218376237,"version":"build-2065373602"},"reference-count":39,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T00:00:00Z","timestamp":1620172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Appenrodt Stiftung","award":["X"],"award-info":[{"award-number":["X"]}]},{"DOI":"10.13039\/501100003107","name":"Bundesministerium f\u00fcr Gesundheit","doi-asserted-by":"publisher","award":["01EO1302"],"award-info":[{"award-number":["01EO1302"]}],"id":[{"id":"10.13039\/501100003107","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hochschulinterne Leistungsf\u00f6rderung (HiLF) of the Hannover Medical School","award":["X"],"award-info":[{"award-number":["X"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Biliary atresia (BA) is a neonatal cholangiopathy characterized by progressive destruction of the biliary system resulting in liver cirrhosis. Residual bile drainage can temporarily be achieved through Kasai portoenterostomy (KPE) and some children show long-term survival with their native liver. However, most children eventually require liver transplantation (LTX). As several growth factors (GF) and chemokines have been shown to promote fibrogenesis in the liver, we assessed whether GF are predictive for the course of disease. Material and Methods: Liver and sera samples were collected from 49 infants with BA during KPE. Levels of 13 different GF were measured by multiplex immunoassay. Patient outcomes were stratified into favorable (bilirubin &lt; 20 \u00b5mol\/L at 2-year follow-up) and unfavorable (LTX). GF levels were compared between groups by a t-test, correlation coefficients were calculated, and principal component analyses performed. Results: Twenty-two patients showed a favorable and 27 an unfavorable disease course. No relation of GF and outcome could be established. In both groups, high levels of SDF-1alpha\/CXCL12 (1473.0 \u00b1 497.5 pg\/mL), FGF2 (301.2 \u00b1 207.8 pg\/mL), and VEGF-a (209.0 \u00b1 146.4 pg\/mL) levels were measured within the liver, followed (in descending order) by PDGF-bb, LIF, GM-CSF, BDNF, VEGF-d, beta-NGF, IL-7, SCF, PIGF-1, and EGF. Serum marker levels showed much higher mean variation compared to hepatic values and no correlation to the protein microenvironment in the liver. Conclusions: Our study demonstrates high amounts of GF in livers from infants with BA at KPE, but no correlation to the outcome or serum values could be established. Our data suggest that local or systemic GF levels are unsuitable for prediction of the disease course. Collectively, we conclude that in BA the degree of proliferative activity caused by GF is a dismissible factor for the further course of disease.<\/jats:p>","DOI":"10.3390\/jcm10091978","type":"journal-article","created":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T11:06:01Z","timestamp":1620212761000},"page":"1978","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Growth Factors Assessed during Kasai Procedure in Liver and Serum Are Not Predictive for the Postoperative Liver Deterioration in Infants with Biliary Atresia"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7239-8973","authenticated-orcid":false,"given":"Omid","family":"Madadi-Sanjani","sequence":"first","affiliation":[{"name":"Department of Pediatric Surgery, Hannover Medical School, Carl-Neuberg-Stra\u00dfe 1, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Froemmel","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Hannover Medical School, Carl-Neuberg-Stra\u00dfe 1, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1376-7318","authenticated-orcid":false,"given":"Christine S.","family":"Falk","sequence":"additional","affiliation":[{"name":"Institute of Transplant Immunology, Hannover Medical School, Carl-Neuberg-Stra\u00dfe 1, 30625 Hannover, Germany"},{"name":"German Center for Infection Research DZIF, Thematical Translation Unit-Immunocompromized Host (TTU-IICH), 38124 Braunschweig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gertrud","family":"Vieten","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Hannover Medical School, Carl-Neuberg-Stra\u00dfe 1, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claus","family":"Petersen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Hannover Medical School, Carl-Neuberg-Stra\u00dfe 1, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joachim F.","family":"Kuebler","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Hannover Medical School, Carl-Neuberg-Stra\u00dfe 1, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Klemann","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pulmonology, Allergology and Neonatology, Hannover Medical School, Carl-Neuberg-Stra\u00dfe 1, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1186\/1750-1172-8-128","article-title":"Aetiology of Biliary Atresia: What Is Actually Known?","volume":"8","author":"Petersen","year":"2013","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1038\/nrgastro.2015.74","article-title":"Pathogenesis of Biliary Atresia: Defining Biology to Understand Clinical Phenotypes","volume":"12","author":"Asai","year":"2015","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Kohli, R., Cortes, M., Heaton, N.D., and Dhawan, A. Liver Transplantation in Children: State of the Art and Future Perspectives. Arch. Dis. Child., 2017.","DOI":"10.1136\/archdischild-2015-310023"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1016\/j.jhep.2013.01.040","article-title":"Improving Outcomes of Biliary Atresia: French National Series 1986\u20132009","volume":"58","author":"Chardot","year":"2013","journal-title":"J. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1016\/j.jpedsurg.2011.04.013","article-title":"Biliary Atresia in England and Wales: Results of Centralization and New Benchmark","volume":"46","author":"Davenport","year":"2011","journal-title":"J. Pediatr. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1007\/s00595-014-1024-z","article-title":"Effects of Age at Kasai Portoenterostomy on the Surgical Outcome: A Review of the Literature","volume":"45","author":"Nio","year":"2015","journal-title":"Surg. Today"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s12519-018-0139-5","article-title":"Does Time Taken to Achieve Jaundice-Clearance Influence Survival of the Native Liver in Post-Kasai Biliary Atresia?","volume":"14","author":"Nakajima","year":"2018","journal-title":"World J. Pediatr. WJP"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1007\/s00383-016-3951-9","article-title":"Prognostic Values of Serum Bilirubin at 7th Day Post-Kasai for Survival with Native Livers in Patients with Biliary Atresia","volume":"32","author":"Chusilp","year":"2016","journal-title":"Pediatr. Surg. Int."},{"key":"ref_9","first-page":"EC23","article-title":"Diagnostic and Prognostic Significance of Various Histopathological Features in Extrahepatic Biliary Atresia","volume":"10","author":"Muthukanagarajan","year":"2016","journal-title":"J. Clin. Diagn. Res. JCDR"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1055\/s-2008-1038360","article-title":"Analysis of the Pathomorphology of the Intra- and Extrahepatic Biliary System in Biliary Atresia","volume":"18","author":"Zheng","year":"2008","journal-title":"Eur. J. Pediatr. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.cyto.2018.09.010","article-title":"Long-Term Outcome and Necessity of Liver Transplantation in Infants with Biliary Atresia Are Independent of Cytokine Milieu in Native Liver and Serum","volume":"111","author":"Kuebler","year":"2018","journal-title":"Cytokine"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1080\/08977194.2019.1626379","article-title":"Hepatocyte Growth Factor Levels in Livers and Serum at Kasai-Portoenterostomy Are Not Predictive of Clinical Outcome in Infants with Biliary Atresia","volume":"37","author":"Kuebler","year":"2019","journal-title":"Growth Factors Chur Switz."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s00292-018-0558-z","article-title":"Staging of liver fibrosis in biliary atresia: Comparison of Chevallier and Ishak score as well as automated evaluation","volume":"40","author":"Andruszkow","year":"2019","journal-title":"Pathologe"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1002\/lt.21711","article-title":"Prognostic Value of Computerized Quantification of Liver Fibrosis in Children with Biliary Atresia","volume":"15","author":"Pape","year":"2009","journal-title":"Liver Transplant."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1002\/lt.25025","article-title":"Wait-List Mortality of Young Patients with Biliary Atresia: Competing Risk Analysis of a Eurotransplant Registry-Based Cohort","volume":"24","author":"Rogiers","year":"2018","journal-title":"Liver Transplant."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Osawa, Y., Hoshi, M., Yasuda, I., Saibara, T., Moriwaki, H., and Kozawa, O. (2013). Tumor Necrosis Factor-\u03b1 Promotes Cholestasis-Induced Liver Fibrosis in the Mouse through Tissue Inhibitor of Metalloproteinase-1 Production in Hepatic Stellate Cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0065251"},{"key":"ref_17","first-page":"375","article-title":"Tumor necrosis factor-\u03b1 and transforming growth factor-\u03b21 balance liver stem cell differentiation in cholestatic cirrhosis","volume":"38","author":"Yang","year":"2018","journal-title":"Nan Fang Yi Ke Da Xue Xue Bao"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2692","DOI":"10.1111\/ajt.15417","article-title":"Back signaling of HLA class I molecules and T\/NK cell receptor ligands in epithelial cells reflects the rejection-specific microenvironment in renal allograft biopsies","volume":"19","author":"Egelkamp","year":"2019","journal-title":"Am. J. Transplant."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/0168-8278(95)80226-6","article-title":"Histological Grading and Staging of Chronic Hepatitis","volume":"22","author":"Ishak","year":"1995","journal-title":"J. Hepatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1002\/hep.21806","article-title":"Profibrogenic Transforming Growth Factor-Beta\/Activin Receptor-like Kinase 5 Signaling via Connective Tissue Growth Factor Expression in Hepatocytes","volume":"46","author":"Weng","year":"2007","journal-title":"Hepatology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/j.jhep.2007.05.015","article-title":"Differential Effects of TGF-Beta on Connective Tissue Growth Factor (CTGF\/CCN2) Expression in Hepatic Stellate Cells and Hepatocytes","volume":"47","author":"Gressner","year":"2007","journal-title":"J. Hepatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1111\/j.1478-3231.2008.01826.x","article-title":"Connective Tissue Growth Factor: A Fibrogenic Master Switch in Fibrotic Liver Diseases","volume":"28","author":"Gressner","year":"2008","journal-title":"Liver Int."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1089\/153623002321025014","article-title":"SDF-1\u03b1\/CXCR4: A Mechanism for Hepatic Oval Cell Activation and Bone Marrow Stem Cell Recruitment to the Injured Liver of Rats","volume":"4","author":"Hatch","year":"2002","journal-title":"Cloning Stem Cells"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1002\/hep.27649","article-title":"Low-Molecular-Weight Fibroblast Growth Factor 2 Attenuates Hepatic Fibrosis by Epigenetic down-Regulation of Delta-Like1","volume":"61","author":"Pan","year":"2015","journal-title":"Hepatology"},{"key":"ref_25","first-page":"1184","article-title":"High Levels of Serum Basic Fibroblast Growth Factor in Children with Biliary Atresia","volume":"55","author":"Honsawek","year":"2008","journal-title":"Hepatogastroenterology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"308","DOI":"10.5114\/ceh.2019.89476","article-title":"Expression of Vascular Endothelial Growth Factor A in Liver Tissues of Infants with Biliary Atresia","volume":"5","author":"Allam","year":"2019","journal-title":"Clin. Exp. Hepatol."},{"key":"ref_27","first-page":"360","article-title":"Immunolocalization of VEGF A and Its Receptors, VEGFR1 and VEGFR2, in the Liver from Patients with Biliary Atresia","volume":"19","author":"Edom","year":"2011","journal-title":"Appl. Immunohistochem. Mol. Morphol. AIMM"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1002\/jhbp.297","article-title":"Hypoxic-Ischemic Gene Expression Profile in the Isolated Variant of Biliary Atresia","volume":"22","author":"Fratta","year":"2015","journal-title":"J. Hepato-Biliary-Pancreat. Sci."},{"key":"ref_29","first-page":"1013","article-title":"Serum VEGF as a Tumor Marker in Patients with HCV-Related Liver Cirrhosis and Hepatocellular Carcinoma","volume":"33","author":"Mukozu","year":"2013","journal-title":"Anticancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1002\/hep4.1204","article-title":"Reactive Ductules Are Associated with Angiogenesis and Tumor Cell Proliferation in Pediatric Liver Cancer","volume":"2","author":"Lee","year":"2018","journal-title":"Hepatol. Commun."},{"key":"ref_31","first-page":"2357","article-title":"Association between Serum Platelet-Derived Growth Factor BB and Degree of Liver Damage, Fibrosis and Hepatitis B e Antigen (HBeAg) Status in CHB Patients","volume":"59","author":"Diang","year":"2012","journal-title":"Hepatogastroenterology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1038\/labinvest.3780073","article-title":"PDGF-Mediated Chemoattraction of Hepatic Stellate Cells by Bile Duct Segments in Cholestatic Liver Injury","volume":"80","author":"Kinnman","year":"2000","journal-title":"Lab. Investig. J. Tech. Methods Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1097\/SLA.0b013e3182300950","article-title":"The Anatomic Pattern of Biliary Atresia Identified at Time of Kasai Hepatoportoenterostomy and Early Postoperative Clearance of Jaundice Are Significant Predictors of Transplant-Free Survival","volume":"254","author":"Superina","year":"2011","journal-title":"Ann. Surg."},{"key":"ref_34","first-page":"15","article-title":"Expression of Leukemia Inhibitory Factor and Its Receptor during Liver Regeneration in the Adult Rat","volume":"75","author":"Omori","year":"1996","journal-title":"Lab. Investig. J. Tech. Methods Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000447364","article-title":"Brain-Derived Neurotrophic Factor in Children and Adolescents with Cirrhosis Due to Biliary Atresia","volume":"69","author":"Wilasco","year":"2016","journal-title":"Ann. Nutr. Metab."},{"key":"ref_36","first-page":"2368","article-title":"BDNF Gene Polymorphism and Serum Level Correlate with Liver Function in Patients with Hepatitis B-Induced Cirrhosis","volume":"12","author":"Shu","year":"2019","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1002\/hep.28622","article-title":"The Secretin\/Secretin Receptor Axis Modulates Liver Fibrosis through Changes in TGF-\u03921 Biliary Secretion","volume":"64","author":"Wu","year":"2016","journal-title":"Hepatology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1055\/s-2008-1038950","article-title":"Serum Transforming Growth Factor-Beta1 and Epidermal Growth Factor in Biliary Atresia","volume":"18","author":"Vejchapipat","year":"2008","journal-title":"Eur. J. Pediatr. Surg."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1111\/j.1442-200X.2007.02476.x","article-title":"Elevation of Serum Stem-Cell Factor in Postoperative Biliary Atresia","volume":"49","author":"Honsawek","year":"2007","journal-title":"Pediatr. Int."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/9\/1978\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:57:13Z","timestamp":1760162233000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/9\/1978"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,5]]},"references-count":39,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["jcm10091978"],"URL":"https:\/\/doi.org\/10.3390\/jcm10091978","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2021,5,5]]}}}