Genetic Contributions to Biliary Atresia: A Developmental Cholangiopathy

Dominick J. Hellen; Saul J. Karpen

doi:10.1055/a-2153-8927

Seminars in Liver Disease, Inhaltsverzeichnis

Semin Liver Dis 2023; 43(03): 323-335
DOI: 10.1055/a-2153-8927

Review Article

Genetic Contributions to Biliary Atresia: A Developmental Cholangiopathy

Authors

Dominick J. Hellen

¹Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, Georgia
Saul J. Karpen

¹Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, Georgia

Abstract

Biliary atresia (BA) is the most prevalent serious liver disease of infancy and childhood, and the principal indication for liver transplantation in pediatrics. BA is best considered as an idiopathic panbiliary cholangiopathy characterized by obstruction of bile flow and consequent cholestasis presenting during fetal and perinatal periods. While several etiologies have been proposed, each has significant drawbacks that have limited understanding of disease progression and the development of effective treatments. Recently, modern genetic analyses have uncovered gene variants contributing to BA, thereby shifting the paradigm for explaining the BA phenotype from an acquired etiology (e.g., virus, toxin) to one that results from genetically altered cholangiocyte development and function. Herein we review recently reported genetic contributions to BA, highlighting the enhanced representation of variants in biological pathways involving ciliary function, cytoskeletal structure, and inflammation. Finally, we blend these findings as a new framework for understanding the resultant BA phenotype as a developmental cholangiopathy.

Keywords

epigenetics - cilia - cholangiocyte - mutation - cholestasis

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References
1 Mysore KR, Shneider BL, Harpavat S. Biliary atresia as a disease starting in utero: implications for treatment, diagnosis, and pathogenesis. J Pediatr Gastroenterol Nutr 2019; 69 (04) 396-403
2 Harpavat S, Finegold MJ, Karpen SJ. Patients with biliary atresia have elevated direct/conjugated bilirubin levels shortly after birth. Pediatrics 2011; 128 (06) e1428-e1433
3 Bezerra JA, Wells RG, Mack CL. et al. Biliary atresia: clinical and research challenges for the twenty-first century. Hepatology 2018; 68 (03) 1163-1173
4 Asai A, Miethke A, Bezerra JA. Pathogenesis of biliary atresia: defining biology to understand clinical phenotypes. Nat Rev Gastroenterol Hepatol 2015; 12 (06) 342-352 . PMCID: PMC5275434
5 Thomson J. On congenital obliteration of the bile-ducts. Edinburgh Med J 1891; 37 (06) 523
6 Hsiao CH, Chang MH, Chen HL. et al; Taiwan Infant Stool Color Card Study Group. Universal screening for biliary atresia using an infant stool color card in Taiwan. Hepatology 2008; 47 (04) 1233-1240
7 Liao FM, Chang KC, Wu JF, Chen HL, Ni YH, Chang MH. Direct bilirubin and risk of biliary atresia. Pediatrics 2022; 149 (06) e2021053073
8 Shneider BL, Magee JC, Karpen SJ. et al; Childhood Liver Disease Research Network (ChiLDReN). Total serum bilirubin within 3 months of hepatoportoenterostomy predicts short-term outcomes in biliary atresia. J Pediatr 2016; 170: 211-217.e1 , 2
9 Mack CL, Sokol RJ. Unraveling the pathogenesis and etiology of biliary atresia. Pediatr Res 2005; 57 (5, Pt 2): 87R-94R
10 Le M, Reinshagen K, Tomuschat C. Systematic review: the quality of life of patients with biliary atresia. J Pediatr Surg 2022; 57 (12) 934-946
11 Lorent K, Gong W, Koo KA. et al. Identification of a plant isoflavonoid that causes biliary atresia. Sci Transl Med 2015; 7 (286) 286ra67
12 Amarachintha SP, Mourya R, Ayabe H. et al. Biliary organoids uncover delayed epithelial development and barrier function in biliary atresia. Hepatology 2022; 75 (01) 89-103
13 Morton SU, Quiat D, Seidman JG, Seidman CE. Genomic frontiers in congenital heart disease. Nat Rev Cardiol 2022; 19 (01) 26-42
14 Rock N, McLin V. Liver involvement in children with ciliopathies. Clin Res Hepatol Gastroenterol 2014; 38 (04) 407-414
15 Gunay-Aygun M. Liver and kidney disease in ciliopathies. Am J Med Genet C Semin Med Genet 2009; 151C (04) 296-306
16 Khan SA, Muhammad N, Khan MA, Kamal A, Rehman ZU, Khan S. Genetics of human Bardet-Biedl syndrome, an updates. Clin Genet 2016; 90 (01) 3-15
17 Sattar S, Gleeson JG. The ciliopathies in neuronal development: a clinical approach to investigation of Joubert syndrome and Joubert syndrome-related disorders. Dev Med Child Neurol 2011; 53 (09) 793-798
18 Arnon R, Rosenberg HK, Suchy FJ. Caroli disease, Caroli syndrome, and congenital hepatic fibrosis. In: Murray KF, Larson AM. eds, Fibrocystic Diseases of the Liver. 2010: 331-358 . PMID: 33824930
19 Kotalova R, Dusatkova P, Cinek O. et al. Hepatic phenotypes of HNF1B gene mutations: a case of neonatal cholestasis requiring portoenterostomy and literature review. World J Gastroenterol 2015; 21 (08) 2550-2557
20 Girard M, Bizet AA, Lachaux A. et al. DCDC2 mutations cause neonatal sclerosing cholangitis. Hum Mutat 2016; 37 (10) 1025-1029
21 Davit-Spraul A, Gonzales E, Baussan C, Jacquemin E. The Spectrum of Liver Diseases Related to ABCB4 Gene Mutations: Pathophysiology and Clinical aspects. Thieme Medical Publishers; 2010: 134-146
22 Boerrigter MM, Bongers EMHF, Lugtenberg D, Nevens F, Drenth JPH. Polycystic liver disease genes: practical considerations for genetic testing. Eur J Med Genet 2021; 64 (03) 104160
23 Wills ES, Roepman R, Drenth JP. Polycystic liver disease: ductal plate malformation and the primary cilium. Trends Mol Med 2014; 20 (05) 261-270
24 Cano-Gamez E, Trynka G. From GWAS to function: using functional genomics to identify the mechanisms underlying complex diseases. Front Genet 2020; 11: 424
25 Ben-Ami M, Perlitz Y, Shalev S, Shajrawi I, Muller F. Prenatal diagnosis of extrahepatic biliary duct atresia. Prenat Diagn 2002; 22 (07) 583-585
26 Davenport M, Savage M, Mowat AP, Howard ER. Biliary atresia splenic malformation syndrome: an etiologic and prognostic subgroup. Surgery 1993; 113 (06) 662-668
27 Whitten WW, Adie GC. Congenital biliary atresia; report of three cases; two occurring in one family. J Pediatr 1952; 40 (05) 539-548
28 Gunasekaran TS, Hassall EG, Steinbrecher UP, Yong SL. Recurrence of extrahepatic biliary atresia in two half sibs. Am J Med Genet 1992; 43 (03) 592-594
29 Kobayashi K, Kubota M, Okuyama N, Hirayama Y, Watanabe M, Sato K. Mother-to-daughter occurrence of biliary atresia: a case report. J Pediatr Surg 2008; 43 (08) 1566-1568
30 Amendola M, Squires JE. Pediatric Genetic Cholestatic Liver Disease Overview. National Library of Medicine; 2022: 2-16
31 Watkins WS, Hernandez EJ, Wesolowski S. et al. De novo and recessive forms of congenital heart disease have distinct genetic and phenotypic landscapes. Nat Commun 2019; 10 (01) 4722
32 Jin SC, Homsy J, Zaidi S. et al. Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands. Nat Genet 2017; 49 (11) 1593-1601
33 Antoniou A, Raynaud P, Cordi S. et al. Intrahepatic bile ducts develop according to a new mode of tubulogenesis regulated by the transcription factor SOX9. Gastroenterology 2009; 136 (07) 2325-2333
34 El-Gohary Y, Zhao K, Gittes GK. Embryologic development of the liver, biliary tract, and pancreas. Blumgart's Surgery of the Liver, Biliary Tract, and Pancreas 2017; 2: 17-31
35 Tsai EA, Grochowski CM, Loomes KM. et al. Replication of a GWAS signal in a Caucasian population implicates ADD3 in susceptibility to biliary atresia. Hum Genet 2014; 133 (02) 235-243
36 Wang Z, Xie X, Zhao J. et al. The intragenic epistatic association of ADD3 with biliary atresia in Southern Han Chinese population. Biosci Rep 2018; 38 (03) BSR20171688
37 Ye Y, Li Z, Feng Q. et al. Downregulation of microRNA-145 may contribute to liver fibrosis in biliary atresia by targeting ADD3. PLoS One 2017; 12 (09) e0180896
38 Cheng G, Tang CS-M, Wong EH-M. et al. Common genetic variants regulating ADD3 gene expression alter biliary atresia risk. J Hepatol 2013; 59 (06) 1285-1291
39 Bai M-R, Niu W-B, Zhou Y. et al. Association of common variation in ADD3 and GPC1 with biliary atresia susceptibility. Aging (Albany NY) 2020; 12 (08) 7163-7182
40 Ningappa M, So J, Glessner J. et al. The role of ARF6 in biliary atresia. PLoS One 2015; 10 (09) e0138381
41 Laochareonsuk W, Kayasut K, Surachat K, Chiengkriwate P, Sangkhathat S. Impact of EFEMP1 on the survival outcome of biliary atresia in Thai infants. Sci Rep 2022; 12 (01) 15603
42 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 (08) e1007532
43 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 (05) 1107-1115.e3
44 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) 1661-1664
45 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: 590-595
46 Bai M-R, Pei H-Y, Zhou Y. et al. Association analysis and functional follow-up identified common variants of JAG1 accounting for risk to biliary atresia. Front Genet 2023;
47 Zeng S, Sun P, Chen Z. et al. Association between single nucleotide polymorphisms in the ADD3 gene and susceptibility to biliary atresia. PLoS One 2014; 9 (10) e107977
48 Li T-F, Ke X-Y, Zhang Y-R, Zhan J-H. The correlation between rs2501577 gene polymorphism and biliary atresia: a systematic review and meta-analysis. Pediatr Surg Int 2023; 39 (01) 206
49 Garcia-Barceló M-M, Yeung M-Y, Miao X-P. et al. Genome-wide association study identifies a susceptibility locus for biliary atresia on 10q24.2. Hum Mol Genet 2010; 19 (14) 2917-2925
50 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 (05) 524-530
51 Ye Y, Wu W, Zheng J, Zhang L, Wang B. Role of long non-coding RNA-adducin 3 antisense RNA1 in liver fibrosis of biliary atresia. Bioengineered 2022; 13 (03) 6222-6230
52 Llewellyn J, Roberts E, Liu C, Naji A, Assoian RK, Wells RG. Efemp1 modulates elastic fiber formation and mechanics of the extrahepatic bile duct. bioRxiv 2021 . Doi: 2021.12.05.471313
53 Van Acker T, Tavernier J, Peelman F. The small GTPase Arf6: an overview of its mechanisms of action and of its role in host–pathogen interactions and innate immunity. Int J Mol Sci 2019; 20 (09) 2209
54 Filmus J, Capurro M. The role of glypicans in Hedgehog signaling. Matrix Biol 2014; 35: 248-252
55 Valenta T, Hausmann G, Basler K. The many faces and functions of β-catenin. EMBO J 2012; 31 (12) 2714-2736
56 Warthen DM, Moore EC, Kamath BM. et al. Jagged1 (JAG1) mutations in Alagille syndrome: increasing the mutation detection rate. Hum Mutat 2006; 27 (05) 436-443
57 Kamath BM, Bauer RC, Loomes KM. et al. NOTCH2 mutations in Alagille syndrome. J Med Genet 2012; 49 (02) 138-144
58 Lechuga S, Amin PH, Wolen AR, Ivanov AI. Adducins inhibit lung cancer cell migration through mechanisms involving regulation of cell-matrix adhesion and cadherin-11 expression. Biochim Biophys Acta Mol Cell Res 2019; 1866 (03) 395-408
59 Sabe H. Requirement for Arf6 in cell adhesion, migration, and cancer cell invasion. J Biochem 2003; 134 (04) 485-489
60 Song EL, Hou YP, Yu SP. et al. EFEMP1 expression promotes angiogenesis and accelerates the growth of cervical cancer in vivo. Gynecol Oncol 2011; 121 (01) 174-180
61 Zong Y, Panikkar A, Xu J. et al. Notch signaling controls liver development by regulating biliary differentiation. Development 2009; 136 (10) 1727-1739
62 Mansini AP, Peixoto E, Thelen KM, Gaspari C, Jin S, Gradilone SA. The cholangiocyte primary cilium in health and disease. Biochim Biophys Acta Mol Basis Dis 2018; 1864 (4, Pt B): 1245-1253
63 Gigante ED, Caspary T. Signaling in the primary cilium through the lens of the Hedgehog pathway. Wiley Interdiscip Rev Dev Biol 2020; 9 (06) e377
64 Bergmann C. Genetics of autosomal recessive polycystic kidney disease and its differential diagnoses. Front Pediatr 2018; 5: 221
65 Cornec-Le Gall E, Torres VE, Harris PC. Genetic complexity of autosomal dominant polycystic kidney and liver diseases. J Am Soc Nephrol 2018; 29 (01) 13-23
66 Katsanis N, Ansley SJ, Badano JL. et al. Triallelic inheritance in Bardet-Biedl syndrome, a Mendelian recessive disorder. Science 2001; 293 (5538) 2256-2259
67 Frassetto R, Parolini F, Marceddu S. et al. Intrahepatic bile duct primary cilia in biliary atresia. Hepatol Res 2018; 48 (08) 664-674
68 Karjoo S, Hand NJ, Loarca L, Russo PA, Friedman JR, Wells RG. Extrahepatic cholangiocyte cilia are abnormal in biliary atresia. J Pediatr Gastroenterol Nutr 2013; 57 (01) 96-101
69 Chu AS, Russo PA, Wells RG. Cholangiocyte cilia are abnormal in syndromic and non-syndromic biliary atresia. Mod Pathol 2012; 25 (05) 751-757
70 Lam W-Y, Tang CS-M, So M-T. et al. Identification of a wide spectrum of ciliary gene mutations in nonsyndromic biliary atresia patients implicates ciliary dysfunction as a novel disease mechanism. EBioMedicine 2021; 71: 103530
71 So J, Ningappa M, Glessner J. et al. Biliary-atresia-associated Mannosidase-1-alpha-2 gene regulates biliary and ciliary morphogenesis and laterality. Front Physiol 2020; 11: 538701
72 Berauer JP, Mezina AI, Okou DT. et al; Childhood Liver Disease Research Network (ChiLDReN). Identification of polycystic kidney disease 1 like 1 gene variants in children with biliary atresia splenic malformation syndrome. Hepatology 2019; 70 (03) 899-910
73 Blair-Reid SA. An Investigation of the Ciliary Protein PKHD1 in Cyst Development in Liver Disease: Clues to the Pathogenesis of Biliary Atresia. University of Birmingham; 2010
74 Afzelius BA. Situs inversus and ciliary abnormalities. What is the connection?. Int J Dev Biol 1995; 39 (05) 839-844
75 Ningappa M, Adenuga M, Ngo KA. et al. Mechanisms of impaired lung development and ciliation in mannosidase-1-alpha-2 (Man1a2) mutants. Front Physiol 2021; 12: 658518
76 Sok P, Sabo A, Almli LM. et al; University of Washington Center for Mendelian Genomics, NISC Comparative Sequencing Program, the National Birth Defects Prevention Study. Exome-wide assessment of isolated biliary atresia: a report from the National Birth Defects Prevention Study using child-parent trios and a case-control design to identify novel rare variants. Am J Med Genet A 2023; 191 (06) 1546-1556
77 Delling M, DeCaen PG, Doerner JF, Febvay S, Clapham DE. Primary cilia are specialized calcium signalling organelles. Nature 2013; 504 (7479) 311-314
78 DeCaen PG, Delling M, Vien TN, Clapham DE. Direct recording and molecular identification of the calcium channel of primary cilia. Nature 2013; 504 (7479) 315-318
79 Field S, Riley KL, Grimes DT. et al. Pkd1l1 establishes left-right asymmetry and physically interacts with Pkd2. Development 2011; 138 (06) 1131-1142
80 Vogel P, Read R, Hansen GM, Freay LC, Zambrowicz BP, Sands AT. Situs inversus in Dpcd/Poll-/-, Nme7-/-, and Pkd1l1-/- mice. Vet Pathol 2010; 47 (01) 120-131
81 Hellen DJ, Bennett A, Malla S. et al. Liver-restricted deletion of the biliary atresia candidate gene Pkd1l1 causes bile duct dysmorphogenesis and ciliopathy. Hepatology 2022; 10: 1097
82 Tsai EA, Grochowski CM, Falsey AM. et al. Heterozygous deletion of FOXA2 segregates with disease in a family with heterotaxy, panhypopituitarism, and biliary atresia. Hum Mutat 2015; 36 (06) 631-637
83 Jacquemin E, Cresteil D, Raynaud N, Hadchouel M. CFCI gene mutation and biliary atresia with polysplenia syndrome. J Pediatr Gastroenterol Nutr 2002; 34 (03) 326-327
84 Davit-Spraul A, Baussan C, Hermeziu B, Bernard O, Jacquemin E. CFC1 gene involvement in biliary atresia with polysplenia syndrome. J Pediatr Gastroenterol Nutr 2008; 46 (01) 111-112
85 Namavarian A, Eid A, Goh ESY, Thakur V. A novel DNAH11 variant segregating in a sibship with heterotaxy and implications for genetic counseling. Mol Genet Genomic Med 2020; 8 (09) e1358
86 Schön P, Tsuchiya K, Lenoir D. et al. Identification, genomic organization, chromosomal mapping and mutation analysis of the human INV gene, the ortholog of a murine gene implicated in left-right axis development and biliary atresia. Hum Genet 2002; 110 (02) 157-165
87 Bochkis IM, Rubins NE, White P, Furth EE, Friedman JR, Kaestner KH. Hepatocyte-specific ablation of Foxa2 alters bile acid homeostasis and results in endoplasmic reticulum stress. Nat Med 2008; 14 (08) 828-836
88 Li Z, White P, Tuteja G, Rubins N, Sackett S, Kaestner KH. Foxa1 and Foxa2 regulate bile duct development in mice. J Clin Invest 2009; 119 (06) 1537-1545
89 Masyuk AI, Masyuk TV, Splinter PL, Huang BQ, Stroope AJ, LaRusso NF. Cholangiocyte cilia detect changes in luminal fluid flow and transmit them into intracellular Ca2+ and cAMP signaling. Gastroenterology 2006; 131 (03) 911-920
90 Hukkinen M, Pihlajoki M, Pakarinen MP. Predicting Native Liver Injury and Survival in Biliary Atresia. Elsevier; 2020: 150943
91 Arikan C, Berdeli A, Kilic M, Tumgor G, Yagci RV, Aydogdu S. Polymorphisms of the ICAM-1 gene are associated with biliary atresia. Dig Dis Sci 2008; 53 (07) 2000-2004
92 He S, Yang Y, Meng L. et al. VEGFA rs3025039 and biliary atresia susceptibility in Chinese population: a systematic review and meta-analysis. World J Pediatr Surg 2022; 5 (01) e000344
93 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 (04) e22342
94 Liu B, Wei J, Li M. et al. Association of common genetic variants in VEGFA with biliary atresia susceptibility in Northwestern Han Chinese. Gene 2017; 628: 87-92
95 Glaser SS, Gaudio E, Alpini G. Vascular factors, angiogenesis and biliary tract disease. Curr Opin Gastroenterol 2010; 26 (03) 246-250
96 Syal G, Fausther M, Dranoff JA. Advances in cholangiocyte immunobiology. Am J Physiol Gastrointest Liver Physiol 2012; 303 (10) G1077-G1086
97 Yokomori H, Oda M, Ogi M. et al. Expression of adhesion molecules on mature cholangiocytes in canal of Hering and bile ductules in wedge biopsy samples of primary biliary cirrhosis. World J Gastroenterol 2005; 11 (28) 4382-4389
98 Swaim CD, Scott AF, Canadeo LA, Huibregtse JM. Extracellular ISG15 signals cytokine secretion through the LFA-1 integrin receptor. Mol Cell 2017; 68 (03) 581-590.e5
99 Zhao R, Song Z, Dong R, Li H, Shen C, Zheng S. Polymorphism of ITGB2 gene 3′-UTR+145C/A is associated with biliary atresia. Digestion 2013; 88 (02) 65-71
100 Liu F, Zeng J, Zhu D. et al. PDGFA gene rs9690350 polymorphism increases biliary atresia risk in Chinese children. Biosci Rep 2020; 40 (07) BSR20200068
101 Cofer ZC, Cui S, EauClaire SF. et al. Methylation microarray studies highlight PDGFA expression as a factor in biliary atresia. PLoS One 2016; 11 (03) e0151521
102 Uhlén M, Fagerberg L, Hallström BM. et al. Proteomics. Tissue-based map of the human proteome. Science 2015; 347 (6220) 1260419
103 Mariotti V, Fiorotto R, Cadamuro M, Fabris L, Strazzabosco M. New insights on the role of vascular endothelial growth factor in biliary pathophysiology. JHEP Reports; 2021: 100251
104 Arikan C, Berdeli A, Ozgenc F, Tumgor G, Yagci RV, Aydogdu S. Positive association of macrophage migration inhibitory factor gene-173G/C polymorphism with biliary atresia. J Pediatr Gastroenterol Nutr 2006; 42 (01) 77-82
105 Rajagopalan R, Tsai EA, Grochowski CM. et al. Exome sequencing in individuals with isolated biliary atresia. Sci Rep 2020; 10 (01) 2709
106 Lysy PA, Sibille C, Gillerot Y, Smets F, Sokal EM. Partial proximal 10q trisomy: a new case associated with biliary atresia. Hereditas 2007; 144 (05) 191-194
107 Alpert LI, Strauss L, Hirschhorn K. Neonatal hepatitis and biliary atresia associated with trisomy 17-18 syndrome. N Engl J Med 1969; 280 (01) 16-20
108 Ikeda S, Sera Y, Yoshida M. et al. Extrahepatic biliary atresia associated with trisomy 18. Pediatr Surg Int 1999; 15 (02) 137-138
109 Chlapoutaki CE, Franchi-Abella S, Habes D, Pariente D. Custom-made covered transjugular intrahepatic portosystemic shunt (TIPS) in an infant with trisomy 22 and biliary atresia. Pediatr Radiol 2009; 39 (07) 739-742
110 Silveira TR, Salzano FM, Howard ER, Mowat AP. Congenital structural abnormalities in biliary atresia: evidence for etiopathogenic heterogeneity and therapeutic implications. Acta Paediatr 1991; 80 (12) 1192-1199
111 Leyva-Vega M, Gerfen J, Thiel BD. et al. Genomic alterations in biliary atresia suggest region of potential disease susceptibility in 2q37.3. Am J Med Genet A 2010; 152A (04) 886-895
112 Rossi M, Labalme A, Cordier MP. et al. Mosaic 18q21.2 deletions including the TCF4 gene: a clinical report. Am J Med Genet A 2012; 158A (12) 3174-3181
113 Chawla V, Anagnost MR, Eldemerdash A-E. et al. A novel case of biliary atresia in a premature neonate with 1p36 deletion syndrome. J Investig Med High Impact Case Rep 2018; 6: 2324709618790613
114 Girard M, Panasyuk G. Genetics in biliary atresia. Curr Opin Gastroenterol 2019; 35 (02) 73-81
115 Hand NJ, Horner AM, Master ZR. et al. MicroRNA profiling identifies miR-29 as a regulator of disease-associated pathways in experimental biliary atresia. J Pediatr Gastroenterol Nutr 2012; 54 (02) 186-192
116 Xiao Y, Wang J, Chen Y. et al. Up-regulation of miR-200b in biliary atresia patients accelerates proliferation and migration of hepatic stellate cells by activating PI3K/Akt signaling. Cell Signal 2014; 26 (05) 925-932
117 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 (03) 905-914
118 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 (01) 26969
119 Udomsinprasert W, Poovorawan Y, Chongsrisawat V, Vejchapipat P, Jittikoon J, Honsawek S. Leukocyte mitochondrial DNA copy number as a potential biomarker indicating poor outcome in biliary atresia and its association with oxidative DNA damage and telomere length. Mitochondrion 2019; 47: 1-9
120 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 (03) 986-990
121 Koh H, Park G-S, Shin S-M. et al. Mitochondrial mutations in cholestatic liver disease with biliary atresia. Sci Rep 2018; 8 (01) 905
122 Tiao M-M, Lin T-K, Kuo F-Y. et al. Early stage of biliary atresia is associated with significant changes in 8-hydroxydeoxyguanosine and mitochondrial copy number. J Pediatr Gastroenterol Nutr 2007; 45 (03) 329-334
123 Tiao MM, Liou CW, Huang LT. et al. Associations of mitochondrial haplogroups b4 and e with biliary atresia and differential susceptibility to hydrophobic bile Acid. PLoS Genet 2013; 9 (08) e1003696
124 Fabre A, Roman C, Roquelaure B. Somatic mutation, a cause of biliary atresia: a hypothesis. Med Hypotheses 2017; 102: 91-93
125 Fischler B, Czubkowski P, Dezsofi A. et al. Incidence, impact and treatment of ongoing CMV infection in patients with biliary atresia in four European centres. J Clin Med 2022; 11 (04) 945
126 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 (02) 109-113
127 Riepenhoff-Talty M, Gouvea V, Evans MJ. et al. Detection of group C rotavirus in infants with extrahepatic biliary atresia. J Infect Dis 1996; 174 (01) 8-15
128 Tyler KL, Sokol RJ, Oberhaus SM. et al. Detection of reovirus RNA in hepatobiliary tissues from patients with extrahepatic biliary atresia and choledochal cysts. Hepatology 1998; 27 (06) 1475-1482
129 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) 2278-2284
130 Lakshminarayanan B, Davenport M. Biliary atresia: a comprehensive review. J Autoimmun 2016; 73: 1-9
131 Bezerra JA, Spino C, Magee JC. et al; Childhood Liver Disease Research and Education Network (ChiLDREN). Use of corticosteroids after hepatoportoenterostomy for bile drainage in infants with biliary atresia: the START randomized clinical trial. JAMA 2014; 311 (17) 1750-1759
132 Shen O, Sela HY, Nagar H. et al. Prenatal diagnosis of biliary atresia: a case series. Early Hum Dev 2017; 111: 16-19
133 Xu X, Zhan J. Biliary atresia in twins: a systematic review and meta-analysis. Pediatr Surg Int 2020; 36 (08) 953-958
134 Arikan C, Berdeli A, Ozgenc F, Aydogdu S, Yagci R. The positive association of MIF gene− 173 G/C polymorphism with biliary atresia in Turkish patients: PH1–19. Ann Hum Genet 2005; 40 (05) 675-676 . PMID: 28657145
135 Sadek KH, Ezzat S, Abdel-Aziz SA, Alaraby H, Mosbeh A, Abdel-Rahman MH. Macrophage migration inhibitory factor (MIF) gene promotor polymorphism is associated with increased fibrosis in biliary atresia patients, but not with disease susceptibility. Ann Hum Genet 2017; 81 (05) 177-183
136 Yang Y, Jin Z, Dong R. et al. MicroRNA-29b/142-5p contribute to the pathogenesis of biliary atresia by regulating the IFN-γ gene. Cell Death Dis 2018; 9 (05) 545
137 Dong R, Zhao R, Zheng S. Changes in epigenetic regulation of CD4+ T lymphocytesin biliary atresia. Pediatr Res 2011; 70 (06) 555-559
138 Udomsinprasert W, Kitkumthorn N, Mutirangura A, Chongsrisawat V, Poovorawan Y, Honsawek S. Association between promoter hypomethylation and overexpression of autotaxin with outcome parameters in biliary atresia. PLoS One 2017; 12 (01) e0169306
139 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 (06) G989-G997
140 Zhao D, Luo Y, Xia Y, Zhang J-J, Xia Q. MicroRNA-19b expression in human biliary atresia specimens and its role in BA-related fibrosis. Dig Dis Sci 2017; 62 (03) 689-698
141 Goldschmidt I, Thum T, Baumann U. Circulating miR-21 and miR-29a as markers of disease severity and etiology in cholestatic pediatric liver disease. J Clin Med 2016; 5 (03) 28
142 Shen W, Chen G, Dong R, Zhao R, Zheng S. MicroRNA-21/PTEN/Akt axis in the fibrogenesis of biliary atresia. J Pediatr Surg 2014; 49 (12) 1738-1741
143 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: 10
144 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 (05) 518-523
145 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 (06) 1007-1016
146 Hsu Y-A, Lin C-H, Lin H-J. et al. Effect of microRNA-155 on the interferon-gamma signaling pathway in biliary atresia. Chin J Physiol 2016; 59 (06) 315-322
147 Yoneyama T, Ueno T, Masahata K. et al. Elevation of microRNA-214 is associated with progression of liver fibrosis in patients with biliary atresia. Pediatr Surg Int 2022; 38 (01) 115-122
148 Gawish E, El-Monem EA, El-Abd M, Sobhy GA, Ghanem H. MicroRNA-499 rs3746444 polymorphism in Egyptian children with biliary atresia. Clin Exp Hepatol 2020; 6 (03) 263-269
149 Shan Y, Shen N, Han L. et al. MicroRNA-499 Rs3746444 polymorphism and biliary atresia. Dig Liver Dis 2016; 48 (04) 423-428
150 Dong R, Shen Z, Zheng C, Chen G, Zheng S. Serum microRNA microarray analysis identifies miR-4429 and miR-4689 are potential diagnostic biomarkers for biliary atresia. Sci Rep 2016; 6 (01) 21084