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Current Pediatric Reviews


ISSN (Print): 1573-3963
ISSN (Online): 1875-6336

Review Article

Update on Etiology and Pathogenesis of Biliary Atresia

Author(s): Patrícia Quelhas, Carlos Cerski and Jorge Luiz dos Santos*

Volume 19, Issue 1, 2023

Published on: 24 June, 2022

Page: [48 - 67] Pages: 20

DOI: 10.2174/1573396318666220510130259

Price: $65


Biliary atresia is a rare inflammatory sclerosing obstructive cholangiopathy that initiates in infancy as complete choledochal blockage and progresses to the involvement of intrahepatic biliary epithelium. Growing evidence shows that biliary atresia is not a single entity with a single etiology but a phenotype resulting from multifactorial events whose common path is obliterative cholangiopathy. The etiology of biliary atresia has been explained as resulting from genetic variants, toxins, viral infection, chronic inflammation or bile duct lesions mediated by autoimmunity, abnormalities in the development of the bile ducts, and defects in embryogenesis, abnormal fetal or prenatal circulation and susceptibility factors. It is increasingly evident that the genetic and epigenetic predisposition combined with the environmental factors to which the mother is exposed are potential triggers for biliary atresia. There is also an indication that a progressive thickening of the arterial middle layer occurs in this disease, suggestive of vascular remodeling and disappearance of the interlobular bile ducts. It is suggested that the hypoxia/ischemia process can affect portal structures in biliary atresia and is associated with both the extent of biliary proliferation and the thickening of the medial layer.

Keywords: Biliary atresia, hypoxia, ischemia, etiology, genetics, epigenetics, gut microbiota, immunity.

Graphical Abstract
Lakshminarayanan B, Davenport M. Biliary atresia: A comprehensive review. J Autoimmun 2016; 73: 1-9.
[] [PMID: 27346637]
Baek SH, Kang JM, Ihn K, Han SJ, Koh H, Ahn JG. The epidemiology and etiology of cholangitis after kasai portoenterostomy in patients with biliary atresia. J Pediatr Gastroenterol Nutr 2020; 70(2): 171-7.
[] [PMID: 31978011]
Harpavat S, Finegold MJ, Karpen SJ. Patients with biliary atresia have elevated direct/conjugated bilirubin levels shortly after birth. Pediatrics 2011; 128(6): e1428-33.
[] [PMID: 22106076]
Santos JL, Kieling CO, Meurer L, et al. The extent of biliary proliferation in liver biopsies from patients with biliary atresia at portoenter-ostomy is associated with the postoperative prognosis. J Pediatr Surg 2009; 44(4): 695-701.
[] [PMID: 19361628]
Kasai M, Suzuki H, Ohashi E, Ohi R, Chiba T, Okamoto A. Technique and results of operative management of biliary atresia. World J Surg 1978; 2(5): 571-9.
[] [PMID: 741761]
Wehrman A, Waisbourd-Zinman O, Wells RG. Recent advances in understanding biliary atresia. F1000 Res 2019; 8: 8.
[] [PMID: 30828434]
Nizery L, Chardot C, Sissaoui S, et al. Biliary atresia: Clinical advances and perspectives. Clin Res Hepatol Gastroenterol 2016; 40(3): 281-7.
[] [PMID: 26775892]
Kilgore A, Mack CL. Update on investigations pertaining to the pathogenesis of biliary atresia. Pediatr Surg Int 2017; 33(12): 1233-41.
[] [PMID: 29063959]
Girard M, Jannot AS, Besnard M, et al. Polynesian ecology determines seasonality of biliary atresia. Hepatology 2011; 54(5): 1893-4.
[] [PMID: 21748760]
Sanchez-Valle A, Kassira N, Varela VC, Radu SC, Paidas C, Kirby RS. Biliary atresia: Epidemiology, genetics, clinical update, and public health perspective. Adv Pediatr 2017; 64(1): 285-305.
[] [PMID: 28688594]
Davenport M. Biliary atresia: From Australia to the zebrafish. J Pediatr Surg 2016; 51(2): 200-5.
[] [PMID: 26653951]
Luo Z, Jegga AG, Bezerra JA. Gene-disease associations identify a connectome with shared molecular pathways in human cholangiopa-thies. Hepatology 2018; 67(2): 676-89.
[] [PMID: 28865156]
dos Santos JL, da Silveira TR, da Silva VD, Cerski CT, Wagner MB. Medial thickening of hepatic artery branches in biliary atresia. A mor-phometric study. J Pediatr Surg 2005; 40(4): 637-42.
[] [PMID: 15852270]
Uflacker R, Pariente DM. Angiographic findings in biliary atresia. Cardiovasc Intervent Radiol 2004; 27(5): 486-90.
[] [PMID: 15383852]
Humphrey TM, Stringer MD. Biliary atresia: US diagnosis. Radiology 2007; 244(3): 845-51.
[] [PMID: 17709832]
Kim WS, Cheon JE, Youn BJ, et al. Hepatic arterial diameter measured with US: Adjunct for US diagnosis of biliary atresia. Radiology 2007; 245(2): 549-55.
[] [PMID: 17890351]
Caruso S, Miraglia R, Milazzo M, et al. Multidetector computed tomography hepatic findings in children with end-stage biliary atresia. Eur Radiol 2010; 20(6): 1468-75.
[] [PMID: 20016905]
El-Guindi MA, Sira MM, Konsowa HA, El-Abd OL, Salem TA. Value of hepatic subcapsular flow by color Doppler ultrasonography in the diagnosis of biliary atresia. J Gastroenterol Hepatol 2013; 28(5): 867-72.
[] [PMID: 23425046]
Kim SS, Kim MJ, Lee MJ, Yoon CS, Han SJ, Koh H. Ultrasonographic findings of type IIIa biliary atresia. Ultrasonography 2014; 33(4): 267-74.
[] [PMID: 25036753]
Ramesh RL, Murthy GV, Jadhav V, Ravindra S. Hepatic subcapsular flow: An early marker in diagnosing biliary atresia. Indian J Radiol Imaging 2015; 25(2): 196-7.
[] [PMID: 25969645]
Davenport M, Muntean A, Hadzic N. Biliary atresia: Clinical phenotypes and aetiological heterogeneity. J Clin Med 2021; 10(23): 5675.
[] [PMID: 34884377]
Silveira TR, Salzano FM, Howard ER, Mowat AP. Congenital structural abnormalities in biliary atresia: Evidence for etiopathogenic heter-ogeneity and therapeutic implications. Acta Paediatr Scand 1991; 80(12): 1192-9.
[] [PMID: 1785291]
Nio M, Kitagawa H. The joint meeting of 54th Annual Congress of the Japanese Society of Pediatric Surgeons and 7th International Sendai Symposium on Biliary Atresia in Sendai Japan. Pediatr Surg Int 2017; 33(12): 1231.
[] [PMID: 28980017]
Frassetto R, Parolini F, Marceddu S, Satta G, Papacciuoli V, Pinna MA, et al. Intrahepatic bile duct primary cilia in biliary atresia. Hepatol Res 2018; 48(8): 664-74.
Arora A, Patidar Y, Khanna R, Alam S, Rastogi A, Negi SS. Cystic biliary atresia: Confounding and intriguing. J Pediatr 2012; 161(3): 562.
[] [PMID: 22683035]
Hill SJ, Clifton MS, Derderian SC, Wulkan ML, Ricketts RR. Cystic biliary atresia: A wolf in sheep’s clothing. Am Surg 2013; 79(9): 870-2.
[] [PMID: 24069978]
Tang J, Zhang D, Liu W, Zeng JX, Yu JK, Gao Y. Differentiation between cystic biliary atresia and choledochal cyst: A retrospective analysis. J Paediatr Child Health 2018; 54(4): 383-9.
[] [PMID: 29105184]
Casaccia G, Bilancioni E, Nahom A, et al. Cystic anomalies of biliary tree in the fetus: Is it possible to make a more specific prenatal diagnosis? J Pediatr Surg 2002; 37(8): 1191-4.
[] [PMID: 12149700]
Vijayaraghavan P, Lal R, Sikora SS, Poddar U, Yachha SK. Experience with choledochal cysts in infants. Pediatr Surg Int 2006; 22(10): 803-7.
[] [PMID: 16947025]
Mackenzie TC, Howell LJ, Flake AW, Adzick NS. The management of prenatally diagnosed choledochal cysts. J Pediatr Surg 2001; 36(8): 1241-3.
[] [PMID: 11479866]
Chen CJ. Clinical and operative findings of choledochal cysts in neonates and infants differ from those in older children. Asian J Surg 2003; 26(4): 213-7.
[] [PMID: 14530107]
Brindley SM, Lanham AM, Karrer FM, Tucker RM, Fontenot AP, Mack CL. Cytomegalovirus-specific T-cell reactivity in biliary atresia at the time of diagnosis is associated with deficits in regulatory T cells. Hepatology 2012; 55(4): 1130-8.
[] [PMID: 22105891]
Goel A, Chaudhari S, Sutar J, et al. Detection of cytomegalovirus in liver tissue by polymerase chain reaction in infants with neonatal cholestasis. Pediatr Infect Dis J 2018; 37(7): 632-6.
[] [PMID: 29389827]
Shah I, Bhatnagar S. Biliary atresia and cytomegalovirus and response to valganciclovir. Indian Pediatr 2012; 49(6): 484-6.
[] [PMID: 22796690]
Pang SY, Dai YM, Zhang RZ, et al. Autoimmune liver disease-related autoantibodies in patients with biliary atresia. World J Gastroenterol 2018; 24(3): 387-96.
[] [PMID: 29391761]
Zhao D, Long XD, Xia Q. Recent advances in etiology of biliary atresia. Clin Pediatr (Phila) 2015; 54(8): 723-31.
[] [PMID: 25187275]
Zani A, Quaglia A, Hadzić N, Zuckerman M, Davenport M. Cytomegalovirus-associated biliary atresia: An aetiological and prognostic subgroup. J Pediatr Surg 2015; 50(10): 1739-45.
[] [PMID: 25824438]
Xu Y, Yu J, Zhang R, et al. The perinatal infection of cytomegalovirus is an important etiology for biliary atresia in China. Clin Pediatr (Phila) 2012; 51(2): 109-13.
[] [PMID: 22144720]
Petersen C, Davenport M. Aetiology of biliary atresia: What is actually known? Orphanet J Rare Dis 2013; 8(1): 128.
[] [PMID: 23987231]
Berauer JP, Mezina AI, Okou DT, et al. Identification of polycystic kidney disease 1 like 1 gene variants in children with biliary atresia splenic malformation syndrome. Hepatology 2019; 70(3): 899-910.
[] [PMID: 30664273]
Durkin N, Deheragoda M, Davenport M. Prematurity and biliary atresia: A 30-year observational study. 2017; 33(12): 1355-61.
Chandra RS. Biliary atresia and other structural anomalies in the congenital polysplenia syndrome. J Pediatr 1974; 85(5): 649-55.
[] [PMID: 4472512]
Schwarz KB, Haber BH, Rosenthal P, et al. Extrahepatic anomalies in infants with biliary atresia: Results of a large prospective North American multicenter study. Hepatology 2013; 58(5): 1724-31.
[] [PMID: 23703680]
Chen Y, Gilbert MA, Grochowski CM, et al. A genome-wide association study identifies a susceptibility locus for biliary atresia on 2p16.1 within the gene EFEMP1. PLoS Genet 2018; 14(8): e1007532.
[] [PMID: 30102696]
Liu F, Zeng J, Zhu D, et al. PDGFA gene rs9690350 polymorphism increases biliary atresia risk in Chinese children. Biosci Rep 2020; 40(7): BSR20200068.
[] [PMID: 32662506]
Zhang H, Leung PSC, Gershwin ME, Ma X. How the biliary tree maintains immune tolerance? Biochim Biophys Acta Mol Basis Dis 2018; 1864(4) (4 Pt B): 1367-73.
[] [PMID: 28844953]
Edom PT, Meurer L, da Silveira TR, Matte U, dos Santos JL. Immunolocalization of VEGF A and its receptors, VEGFR1 and VEGFR2, in the liver from patients with biliary atresia. Appl Immunohistochem Mol Morphol 2011; 19(4): 360-8.
[] [PMID: 21285868]
Fratta LX, Hoss GR, Longo L, et al. Hypoxic-ischemic gene expression profile in the isolated variant of biliary atresia. J Hepatobiliary Pancreat Sci 2015; 22(12): 846-54.
[] [PMID: 26510548]
de Souza AF, Meurer L, da Silveira TR, Gregorio C, Reus N, Uribe C, et al. Angiopoietin 1 and angiopoietin 2 are associated with medial thickening of hepatic arterial branches in biliary atresia. Pediatric Res 2014; 75(1-1): 22-8.
Oetzmann von Sochaczewski C, Pintelon I. Experimentally induced biliary atresia by means of rotavirus-infection is directly linked to severe damage of the microvasculature in the extrahepatic bile duct. Anat Rec (Hoboken) 2019; 302(5): 818-24.
Min J, Ningappa M, So J, Shin D, Sindhi R, Subramaniam S. Systems analysis of biliary atresia through integration of high-throughput biological data. Front Physiol 2020; 11: 966.
Mack CL. What causes biliary atresia? unique aspects of the neonatal immune system provide clues to disease pathogenesis. Cell Mol Gastroenterol Hepatol 2015; 1(3): 267-74.
[] [PMID: 26090510]
Asai A, Miethke A, Bezerra JA. Pathogenesis of biliary atresia: Defining biology to understand clinical phenotypes. Nat Rev Gastroenterol Hepatol 2015; 12(6): 342-52.
[] [PMID: 26008129]
Carmichael SL, Ma C, Van Zutphen AR, Moore CA, Shaw GM. Women’s periconceptional diet and risk of biliary atresia in offspring. Birth Defects Res 2018; 110(12): 994-1000.
[] [PMID: 29762915]
Tam PKH, Yiu RS, Lendahl U, Andersson ER. Cholangiopathies - Towards a molecular understanding. EBioMedicine 2018; 35: 381-93.
[] [PMID: 30236451]
Nakamura K, Tanoue A. Etiology of biliary atresia as a developmental anomaly: Recent advances. J Hepatobiliary Pancreat Sci 2013; 20(5): 459-64.
[] [PMID: 23567964]
Santos JL, Carvalho E, Bezerra JA. Advances in biliary atresia: From patient care to research. Brazilian journal of medical and biological research. Rev Bras Pesqui Med Biol 2010; 43(6): 522-7.
Spence JR, Lange AW, Lin SC, et al. Sox17 regulates organ lineage segregation of ventral foregut progenitor cells. Dev Cell 2009; 17(1): 62-74.
[] [PMID: 19619492]
Zhang RZ, Zeng XH, Lin ZF, et al. Downregulation of Hes1 expression in experimental biliary atresia and its effects on bile duct structure. World J Gastroenterol 2018; 24(29): 3260-72.
[] [PMID: 30090006]
Laochareonsuk W, Chiengkriwate P, Sangkhathat S. Single nucleotide polymorphisms within Adducin 3 and Adducin 3 antisense RNA1 genes are associated with biliary atresia in Thai infants. Pediatr Surg Int 2018; 34(5): 515-20.
[] [PMID: 29508064]
Zeng S, Sun P, Chen Z, Mao J, Wang J, Wang B, et al. Association between single nucleotide polymorphisms in the ADD3 gene and sus-ceptibility to biliary atresia. PLoS One 2014; 9(10): e107977.
Tang V, Cofer ZC, Cui S, Sapp V, Loomes KM, Matthews RP. Loss of a candidate biliary atresia susceptibility gene, add3a, causes biliary developmental defects in zebrafish. J Pediatr Gastroenterol Nutr 2016; 63(5): 524-30.
[] [PMID: 27526058]
Ningappa M, Min J, Higgs BW, Ashokkumar C, Ranganathan S, Sindhi R. Genome-wide association studies in biliary atresia. Wiley Interdiscip Rev Syst Biol Med 2015; 7(5): 267-73.
[] [PMID: 25963027]
Cheng G, Tang CS, Wong EH, et al. Common genetic variants regulating ADD3 gene expression alter biliary atresia risk. J Hepatol 2013; 59(6): 1285-91.
[] [PMID: 23872602]
Ye Y, Li Z, Feng Q, Chen Z, Wu Z, Wang J, et al. Downregulation of microRNA-145 may contribute to liver fibrosis in biliary atresia by targeting ADD3. PLoS One 2017; 12(9): e0180896.
Sira MM, Sira AM, Ehsan NA, Mosbeh A. P-Selectin (CD62P) expression in liver tissue of biliary atresia: A new perspective in etiopatho-genesis. J Pediatr Gastroenterol Nutr 2015; 61(5): 561-7.
[] [PMID: 26102172]
Lin Z, Xie X, Lin H, et al. Epistatic Association of CD14 and NOTCH2 genetic polymorphisms with biliary atresia in a southern Chinese population. Mol Ther Nucleic Acids 2018; 13: 590-5.
[] [PMID: 30439647]
Ke J, Zeng S, Mao J, et al. Common genetic variants of GPC1 gene reduce risk of biliary atresia in a Chinese population. J Pediatr Surg 2016; 51(10): 1661-4.
[] [PMID: 27373597]
Cui S, Leyva-Vega M, Tsai EA, et al. Evidence from human and zebrafish that GPC1 is a biliary atresia susceptibility gene. Gastroenterology 2013; 144(5): 1107-1115.e3.
[] [PMID: 23336978]
Sadek KH, Ezzat S, Abdel-Aziz SA, Alaraby H, Mosbeh A, Abdel-Rahman MH. Macrophage Migration Inhibitory Factor (MIF) gene pro-motor polymorphism is associated with increased fibrosis in biliary atresia patients, but not with disease susceptibility. Ann Hum Genet 2017; 81(5): 177-83.
[] [PMID: 28657145]
Wang J, Wang W, Dong R, et al. Gene expression profiling of extrahepatic ducts in children with biliary atresia. Int J Clin Exp Med 2015; 8(4): 5186-96.
[PMID: 26131092]
Li D, Lu T, Shen C, et al. Expression of fibroblast growth factor 21 in patients with biliary atresia. Cytokine 2016; 83: 13-8.
[] [PMID: 27003131]
Mezina A, Karpen SJ. Genetic contributors and modifiers of biliary atresia. Dig Dis 2015; 33(3): 408-14.
[] [PMID: 26045276]
Ningappa M, So J, Glessner J, et al. The Role of ARF6 in biliary atresia. PLoS One 2015; 10(9): e0138381.
[] [PMID: 26379158]
Liu F, Zeng J, Zhu D, et al. Association of polymorphism in the VEGFA gene 3′-UTR +936T/C with susceptibility to biliary atresia in a Southern Chinese Han population. J Clin Lab Anal 2018; 32(4): e22342.
[] [PMID: 29251369]
Liu B, Wei J, Li M, et al. Association of common genetic variants in VEGFA with biliary atresia susceptibility in Northwestern Han Chi-nese. Gene 2017; 628: 87-92.
[] [PMID: 28710035]
Zahm AM, Hand NJ, Boateng LA, Friedman JR. Circulating microRNA is a biomarker of biliary atresia. J Pediatr Gastroenterol Nutr 2012; 55(4): 366-9.
[] [PMID: 22732895]
Luo Z, Shivakumar P, Mourya R, Gutta S, Bezerra JA. Gene expression signatures associated with survival times of pediatric patients with biliary atresia identify potential therapeutic agents. Gastroenterology 2019; 157(4): 1138-1152.e14.
[] [PMID: 31228442]
Makhmudi A, Kalim AS. Gunadi. microRNA-21 expressions impact on liver fibrosis in biliary atresia patients. BMC Res Notes 2019; 12(1): 189.
[] [PMID: 30925941]
Wang JY, Cheng H, Zhang HY, et al. Suppressing microRNA-29c promotes biliary atresia-related fibrosis by targeting DNMT3A and DNMT3B. Cell Mol Biol Lett 2019; 24(1): 10.
[] [PMID: 30906331]
Zhao D, Luo Y, Xia Y, Zhang JJ, Xia Q. MicroRNA-19b expression in human biliary atresia specimens and its role in ba-related fibrosis. Dig Dis Sci 2017; 62(3): 689-98.
[] [PMID: 28083843]
Hand NJ, Horner AM, Master ZR, et al. MicroRNA profiling identifies miR-29 as a regulator of disease-associated pathways in experi-mental biliary atresia. J Pediatr Gastroenterol Nutr 2012; 54(2): 186-92.
[] [PMID: 22167021]
Bessho K, Shanmukhappa K, Sheridan R, et al. Integrative genomics identifies candidate microRNAs for pathogenesis of experimental biliary atresia. BMC Syst Biol 2013; 7(1): 104.
[] [PMID: 24138927]
Peng X, Yang L, Liu H, et al. Identification of circulating MicroRNAs in biliary atresia by next-generation sequencing. J Pediatr Gastroenterol Nutr 2016; 63(5): 518-23.
[] [PMID: 26960174]
Xiao Y, Wang J, Chen Y, et al. Up-regulation of miR-200b in biliary atresia patients accelerates proliferation and migration of hepatic stal-late cells by activating PI3K/Akt signaling. Cell Signal 2014; 26(5): 925-32.
[] [PMID: 24412919]
Shen WJ, Dong R, Chen G, Zheng S. microRNA-222 modulates liver fibrosis in a murine model of biliary atresia. Biochem Biophys Res Commun 2014; 446(1): 155-9.
[] [PMID: 24569080]
Dong R, Zheng Y, Chen G, Zhao R, Zhou Z, Zheng S. miR-222 overexpression may contribute to liver fibrosis in biliary atresia by targeting PPP2R2A. J Pediatr Gastroenterol Nutr 2015; 60(1): 84-90.
[] [PMID: 25238119]
Cheng G, Chung PH, Chan EK, et al. Patient complexity and genotype-phenotype correlations in biliary atresia: A cross-sectional analysis. BMC Med Genomics 2017; 10(1): 22.
[] [PMID: 28416017]
Zhao R, Dong R, Yang Y, et al. MicroRNA-155 modulates bile duct inflammation by targeting the suppressor of cytokine signaling 1 in biliary atresia. Pediatr Res 2017; 82(6): 1007-16.
[] [PMID: 28355202]
Cofer ZC, Cui S. Methylation microarray studies highlight pdgfa expression as a factor in biliary atresia. PLoS One 2016; 11(3): e0151521.
Udomsinprasert W, Kitkumthorn N, Mutirangura A, Chongsrisawat V, Poovorawan Y, Honsawek S. Association between promoter hy-pomethylation and overexpression of autotaxin with outcome parameters in biliary atresia. PLoS One 2017; 12(1): e0169306.
Li K, Zhang X, Yang L, et al. Foxp3 promoter methylation impairs suppressive function of regulatory T cells in biliary atresia. Am J Physiol Gastrointest Liver Physiol 2016; 311(6): G989-97.
[] [PMID: 27659419]
Dong R, Zhao R, Zheng S, Zheng Y, Xiong S, Chu Y. Abnormal DNA methylation of ITGAL (CD11a) in CD4+ T cells from infants with biliary atresia. Biochem Biophys Res Commun 2012; 417(3): 986-90.
[] [PMID: 22206678]
Udomsinprasert W, Kitkumthorn N, Mutirangura A, Chongsrisawat V, Poovorawan Y, Honsawek S. Global methylation, oxidative stress, and relative telomere length in biliary atresia patients. Sci Rep 2016; 6(1): 26969.
[] [PMID: 27243754]
Matthews RP, Eauclaire SF, Mugnier M, et al. DNA hypomethylation causes bile duct defects in zebrafish and is a distinguishing feature of infantile biliary atresia. Hepatology 2011; 53(3): 905-14.
[] [PMID: 21319190]
Zhang H, Dong P, Guo S, Tao C, Chen W, Zhao W, et al. Hypomethylation in HBV integration regions aids non-invasive surveillance to hepatocellular carcinoma by low-pass genome-wide bisulfite sequencing. BMC Med 2020; 18(1): 200.
Laufer BI, Hwang H, Jianu JM, et al. Low-pass whole genome bisulfite sequencing of neonatal dried blood spots identifies a role for RUNX1 in Down syndrome DNA methylation profiles. Hum Mol Genet 2021; 29(21): 3465-76.
[] [PMID: 33001180]
Lehmann-Werman R, Magenheim J, Moss J, et al. Monitoring liver damage using hepatocyte-specific methylation markers in cell-free circulating DNA. JCI Insight 2018; 3(12): 120687.
[] [PMID: 29925683]
Guo S, Xu L, Chang C, Zhang R, Jin Y, He D. Epigenetic regulation mediated by methylation in the pathogenesis and precision medicine of rheumatoid arthritis. Front Genet 2020; 11: 811.
[] [PMID: 32849810]
Mack CL, Feldman AG, Sokol RJ. Clues to the etiology of bile duct injury in biliary atresia. Semin Liver Dis 2012; 32(4): 307-16.
[] [PMID: 23397531]
Liang J, Wen Z, Zhao J, et al. Association of IL18 genetic polymorphisms with increased risk of Biliary atresia susceptibility in Southern Chinese children. Gene 2018; 677: 228-31.
[] [PMID: 30059753]
Wilasco MIA, Uribe-Cruz C, Santetti D, Fries GR, Dornelles CTL, Silveira TRD. IL-6, TNF-α, IL-10, and nutritional status in pediatric patients with biliary atresia. J Pediatr (Rio J) 2017; 93(5): 517-24.
[] [PMID: 28325677]
Arafa RS, Abdel Haie OM, El-Azab DS, Abdel-Rahman AM, Sira MM. Significant hepatic expression of IL-2 and IL-8 in biliary atresia compared with other neonatal cholestatic disorders. Cytokine 2016; 79: 59-65.
[] [PMID: 26765485]
Dong R, Zheng S. Interleukin-8: A critical chemokine in biliary atresia. J Gastroenterol Hepatol 2015; 30(6): 970-6.
[] [PMID: 25611432]
Klemann C, Schröder A, Dreier A, et al. Interleukin 17, produced by γδ t cells, contributes to hepatic inflammation in a mouse model of biliary atresia and is increased in livers of patients. Gastroenterology 2016; 150(1): 229-241.e5.
[] [PMID: 26404950]
Hill R, Quaglia A, Hussain M, et al. Th-17 cells infiltrate the liver in human biliary atresia and are related to surgical outcome. J Pediatr Surg 2015; 50(8): 1297-303.
[] [PMID: 25783388]
Liu YJ, Li K, Yang L, et al. Dendritic cells regulate Treg-Th17 axis in obstructive phase of bile duct injury in murine biliary atresia. PLoS One 2015; 10(9): e0136214.
Lages CS, Simmons J, Maddox A, et al. The dendritic cell-T helper 17-macrophage axis controls cholangiocyte injury and disease progression in murine and human biliary atresia. Hepatology 2017; 65(1): 174-88.
[] [PMID: 27641439]
Shimada T, Imaizumi T, Shirai K, et al. CCL5 is induced by TLR 3 signaling in HuCCT1 human biliary epithelial cells: Possible involve-ment in the pathogenesis of biliary atresia. Biomed Res 2017; 38(5): 269-76.
Harada K. Sclerosing and obstructive cholangiopathy in biliary atresia: Mechanisms and association with biliary innate immunity. Pediatr Surg Int 2017; 33(12): 1243-8.
[] [PMID: 29039048]
Bednarek J, Traxinger B, Brigham D, et al. Cytokine-producing b cells promote immune-mediated bile duct injury in murine biliary atresia. Hepatology 2018; 68(5): 1890-904.
[] [PMID: 29679373]
Feldman AG, Tucker RM, Fenner EK, Pelanda R, Mack CL. B cell deficient mice are protected from biliary obstruction in the rotavirus-induced mouse model of biliary atresia. PLoS One 2013; 8(8): e73644.
Li J, Bessho K, Shivakumar P, et al. Th2 signals induce epithelial injury in mice and are compatible with the biliary atresia phenotype. J Clin Invest 2011; 121(11): 4244-56.
[] [PMID: 22005305]
Arva NC, Russo PA, Erlichman J, Hancock WW, Haber BA, Bhatti TR. The inflammatory phenotype of the fibrous plate is distinct from the liver and correlates with clinical outcome in biliary atresia. Pathol Res Pract 2015; 211(3): 252-60.
[] [PMID: 25624184]
Sakamoto N, Muraji T, Ohtani H, Masumoto K. The accumulation of regulatory T cells in the hepatic hilar lymph nodes in biliary atresia. Surg Today 2017; 47(10): 1282-6.
[] [PMID: 28293742]
Bove KE, Sheridan R, Fei L, et al. Hepatic Hilar lymph node reactivity at kasai portoenterostomy for biliary atresia: Correlations with age, outcome, and histology of proximal biliary remnant. Pediatr Dev Pathol 2018; 21(1): 29-40.
[] [PMID: 28474973]
Squires JE, Shivakumar P, Mourya R, Bessho K, Walters S, Bezerra JA. Natural killer cells promote long-term hepatobiliary inflammation in a low-dose rotavirus model of experimental biliary atresia. PLoS One 2015; 10(5): e0127191.
Calmus Y, Poupon R. Shaping macrophages function and innate immunity by bile acids: Mechanisms and implication in cholestatic liver diseases. Clin Res Hepatol Gastroenterol 2014; 38(5): 550-6.
Goel P, Bajpai M, Sharma K, Naranje P. Previously undescribed anomalies of hepatic artery and portal venous anatomy in a case of extra-hepatic biliary atresia and its implications. J Indian Assoc Pediatr Surg 2019; 24(4): 294-6.
[] [PMID: 31571764]
Masuya R, Muraji T, Ohtani H, et al. Morphometric demonstration of portal vein stenosis and hepatic arterial medial hypertrophy in patients with biliary atresia. Pediatr Surg Int 2019; 35(5): 529-37.
[] [PMID: 30762106]
Hong SK, Yi NJ, Chang H, et al. The rate of hepatic artery complications is higher in pediatric liver transplant recipients with metabolic liver diseases than with biliary atresia. J Pediatr Surg 2018; 53(8): 1516-22.
[] [PMID: 29861326]
Zhou Y, Jiang M, Tang ST, et al. Laparoscopic finding of a hepatic subcapsular spider-like telangiectasis sign in biliary atresia. World J Gastroenterol 2017; 23(39): 7119-28.
[] [PMID: 29093620]
Vuković J, Grizelj R, Bojanić K, et al. Ductal plate malformation in patients with biliary atresia. Eur J Pediatr 2012; 171(12): 1799-804.
[] [PMID: 22983023]
Desmet VJ. Ludwig symposium on biliary disorders--part I. Pathogenesis of ductal plate abnormalities. Mayo Clin Proc 1998; 73(1): 80-9.
[] [PMID: 9443684]
Desmet VJ. Ductal plates in hepatic ductular reactions. Hypothesis and implications. II. Ontogenic liver growth in childhood. Virchows Arch 2011; 458(3): 261-70.
Allam A, El-Guindi M, Konsowa H, et al. Expression of vascular endothelial growth factor A in liver tissues of infants with biliary atresia. Clin Exp Hepatol 2019; 5(4): 308-16.
[] [PMID: 31893243]
Díaz R, Kim JW, Hui JJ, et al. Evidence for the epithelial to mesenchymal transition in biliary atresia fibrosis. Hum Pathol 2008; 39(1): 102-15.
[] [PMID: 17900655]
Zeisberg M, Yang C, Martino M, et al. Fibroblasts derive from hepatocytes in liver fibrosis via epithelial to mesenchymal transition. J Biol Chem 2007; 282(32): 23337-47.
[] [PMID: 17562716]
Deng YH, Pu CL, Li YC, et al. Analysis of biliary epithelial-mesenchymal transition in portal tract fibrogenesis in biliary atresia. Dig Dis Sci 2011; 56(3): 731-40.
[] [PMID: 20725787]
Fabris L, Brivio S, Cadamuro M, Strazzabosco M. Revisiting epithelial-to-mesenchymal transition in liver fibrosis: Clues for a better understanding of the “reactive” biliary epithelial phenotype. Stem Cells Int 2016; 2016: 2953727.
[] [PMID: 26880950]
Petersen C, Madadi-Sanjani O. Role of viruses in biliary atresia: News from mice and men. Innov Surg Sci 2018; 3(2): 101-6.
[] [PMID: 31579773]
Saito T, Terui K, Mitsunaga T, et al. Evidence for viral infection as a causative factor of human biliary atresia. J Pediatr Surg 2015; 50(8): 1398-404.
[] [PMID: 25979202]
Coots A, Donnelly B, Mohanty SK, McNeal M, Sestak K, Tiao G. Rotavirus infection of human cholangiocytes parallels the murine model of biliary atresia. J Surg Res 2012; 177(2): 275-81.
[] [PMID: 22785360]
Navabi N, Shivakumar P, Eds. Discovery of polyurethane chemicals as new etiopathogenic agents in biliary atresia. Hepatology WILEY 111 RIVER ST, HOBOKEN 07030-5774, NJ USA . 2019.
Patman G. Biliary tract: Newly identified biliatresone causes biliary atresia. Nat Rev Gastroenterol Hepatol 2015; 12(7): 369.
[] [PMID: 26008130]
Koo KA, Lorent K, Gong W, et al. Biliatresone, a reactive natural toxin from dysphania glomulifera and D. littoralis: Discovery of the toxic moiety 1,2-diaryl-2-propenone. Chem Res Toxicol 2015; 28(8): 1519-21.
[] [PMID: 26175131]
Lorent K, Gong W, Koo KA, et al. Identification of a plant isoflavonoid that causes biliary atresia. Sci Transl Med 2015; 7(286): 286ra67.
[] [PMID: 25947162]
Zhao X, Lorent K, Wilkins BJ, et al. Glutathione antioxidant pathway activity and reserve determine toxicity and specificity of the biliary toxin biliatresone in zebrafish. Hepatology 2016; 64(3): 894-907.
[] [PMID: 27102575]
Malik A, Thanekar U, Mourya R, Shivakumar P. Recent developments in etiology and disease modeling of biliary atresia: A narrative review. Dig Med Res 2020; 3(Dec): 3.
[] [PMID: 33615212]
Clarke SF, Murphy EF, O’Sullivan O, et al. Exercise and associated dietary extremes impact on gut microbial diversity. Gut 2014; 63(12): 1913-20.
[] [PMID: 25021423]
Arrieta MC, Stiemsma LT, Amenyogbe N, Brown EM, Finlay B. The intestinal microbiome in early life: Health and disease. Front Immunol 2014; 5: 427.
[] [PMID: 25250028]
Jee J, Mourya R, Shivakumar P, Fei L, Wagner M, Bezerra JA. Cxcr2 signaling and the microbiome suppress inflammation, bile duct inju-ry, and the phenotype of experimental biliary atresia. PLoS One 2017; 12(8): e0182089.
Wang J, Qian T, Jiang J, et al. Gut microbial profile in biliary atresia: A case-control study. J Gastrol Heptol 2020; 35(2): 334-42.
Tessier MEM, Cavallo L, Yeh J, et al. The fecal microbiome in infants with biliary atresia associates with bile flow after kasai portoenter-ostomy. J Pediatr Gastroenterol Nutr 2020; 70(6): 789-95.
[] [PMID: 32443032]
Czech-Schmidt G, Verhagen W, Szavay P, Leonhardt J, Petersen C. Immunological gap in the infectious animal model for biliary atresia. J Surg Res 2000; 101(1): 62-7.
[] [PMID: 11676556]
Carvalho E, Liu C, Shivakumar P, Sabla G, Aronow B, Bezerra JA. Analysis of the biliary transcriptome in experimental biliary atresia. Gastroenterology 2005; 129(2): 713-7.
[] [PMID: 16083724]
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(2): 200-9.
[] [PMID: 15885644]
Mack CL, Tucker RM, Lu BR, et al. Cellular and humoral autoimmunity directed at bile duct epithelia in murine biliary atresia. Hepatology 2006; 44(5): 1231-9.
[] [PMID: 17058262]
Leonhardt J, Stanulla M, von Wasielewski R, et al. Gene expression profile of the infective murine model for biliary atresia. Pediatr Surg Int 2006; 22(1): 84-9.
[] [PMID: 16328331]
Barnes BH, Tucker RM, Wehrmann F, Mack DG, Ueno Y, Mack CL. Cholangiocytes as immune modulators in rotavirus-induced murine biliary atresia. Liver Int 2009; 29(8): 1253-61.
[] [PMID: 19040538]
Jafri M, Donnelly B, Allen S, et al. Cholangiocyte expression of alpha2beta1-integrin confers susceptibility to rotavirus-induced experi-mental biliary atresia. Am J Physiol Gastrointest Liver Physiol 2008; 295(1): G16-26.
[] [PMID: 18436621]
Miethke AG, Saxena V, Shivakumar P, Sabla GE, Simmons J, Chougnet CA. Post-natal paucity of regulatory T cells and control of NK cell activation in experimental biliary atresia. J Hepatol 2010; 52(5): 718-26.
[] [PMID: 20347178]
Lu BR, Brindley SM, Tucker RM, Lambert CL, Mack CL. α-enolase autoantibodies cross-reactive to viral proteins in a mouse model of biliary atresia. Gastroenterology 2010; 139(5): 1753-61.
[] [PMID: 20659472]
Saxena V, Shivakumar P, Sabla G, Mourya R, Chougnet C, Bezerra JA. Dendritic cells regulate natural killer cell activation and epithelial injury in experimental biliary atresia. Sci Transl Med 2011; 3(102): 102ra94.
[] [PMID: 21957172]
Uemura M, Ozawa A, Nagata T, et al. Sox17 haploinsufficiency results in perinatal biliary atresia and hepatitis in C57BL/6 background mice. Development 2013; 140(3): 639-48.
[] [PMID: 23293295]
Waisbourd-Zinman O, Koh H, Tsai S, et al. The toxin biliatresone causes mouse extrahepatic cholangiocyte damage and fibrosis through decreased glutathione and SOX17. Hepatology 2016; 64(3): 880-93.
[] [PMID: 27081925]
Mohanty SK, Donnelly B, Temple H, Tiao GM. Rotavirus-induced mouse model to study biliary atresia and neonatal cholestasis. Methods Mol Biol 2019; 1981: 259-71.
Zhang R, Lin Z, Fu M, et al. The role of neonatal gr-1+ myeloid cells in a murine model of rhesus-rotavirus-induced biliary atresia. Am J Pathol 2018; 188(11): 2617-28.
[] [PMID: 30201498]
Mohanty SK, Donnelly B, Dupree P, et al. A point mutation in the rhesus rotavirus vp4 protein generated through a rotavirus reverse ge-netics system attenuates biliary atresia in the murine model. J Virol 2017; 91(15): e00510-7.
[] [PMID: 28515290]
Mohanty SK, Donnelly B, Lobeck I, et al. The SRL peptide of rhesus rotavirus VP4 protein governs cholangiocyte infection and the murine model of biliary atresia. Hepatology 2017; 65(4): 1278-92.
[] [PMID: 27859498]
Keyzer-Dekker CM, Lind RC, Kuebler JF, et al. Liver fibrosis during the development of biliary atresia: Proof of principle in the murine model. J Pediatr Surg 2015; 50(8): 1304-9.
[] [PMID: 25783404]
Lee JH, Ahn HS, Han S, Swan HS, Lee Y, Kim HJ. Nationwide population-based study showed that the rotavirus vaccination had no impact on the incidence of biliary atresia in Korea. Acta Paediatr 2019; 108(12): 2278-84.
Danial E, Fleck-Derderian S, Rosenthal P. Has rotavirus vaccination decreased the prevalence of biliary atresia? J Clin Gastroenterol 2019; 53(8): e348-51.
[] [PMID: 30222646]
Chung-Davidson YW, Yeh CY, Li W. The sea lamprey as an etiological model for biliary atresia. BioMed Res Int 2015; 2015: 832943.
[] [PMID: 26101777]
Amarachintha SP, Mourya R, Ayabe H, et al. Biliary organoids uncover delayed epithelial development and barrier function in biliary atresia. Hepatology 2022; 75: 89-103.

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