Cholestatic Liver Disease

Section II - Cholestatic Liver Disease

Published online by Cambridge University Press: 19 January 2021

Edited by

Frederick J. Suchy ,

Ronald J. Sokol and

William F. Balistreri

Edited in association with

Jorge A. Bezerra ,

Cara L. Mack and

Benjamin L. Shneider

Show author details

Frederick J. Suchy: Affiliation:
University of Colorado, Children’s Hospital Colorado, Aurora
Ronald J. Sokol: Affiliation:
University of Colorado, Children’s Hospital Colorado, Aurora
William F. Balistreri: Affiliation:
Cincinnati Children’s Hospital Medical Center, Cincinnati
Jorge A. Bezerra: Affiliation:
Cincinnati Children’s Hospital Medical Center, Cincinnati
Cara L. Mack: Affiliation:
University of Colorado, Children’s Hospital Colorado, Aurora
Benjamin L. Shneider: Affiliation:
Texas Children’s Hospital, Houston

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Type: Chapter
Information: Liver Disease in Children , pp. 107 - 272

DOI: https://doi.org/10.1017/9781108918978 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2021

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References

Pearson, HA. Lectures on the diseases of children by Eli Ives, MD of Yale and New Haven: America’s first academic pediatrician. Pediatrics 1986;77:680–6.Google Scholar

Trauner, M, Meier, PJ, Boyer, JL. Molecular pathogenesis of cholestasis. N Engl J Med 1998;339:1217–27.Google Scholar

Koopen, NR, Muller, M, Vonk, RJ, Zimniak, P, Kuipers, F. Molecular mechanisms of cholestasis: causes and consequences of impaired bile formation. Biochim Biophys Acta 1998;1408:1–17.Google Scholar

Suchy, FJ. Neonatal cholestasis. Pediatr Rev 2004;25:388–96.Google Scholar

Fawaz, R, Baumann, U, Ekong, U, et al. Guideline for the Evaluation of Cholestatic Jaundice in Infants: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr 2017;64:154–68.Google Scholar

Sokol, RJ, Shepherd, RW, Superina, R, Bezerra, JA, Robuck, P, Hoofnagle, JH. Screening and outcomes in biliary atresia: summary of a National Institutes of Health workshop. Hepatology 2007;46:566–81.CrossRef Google Scholar PubMed

Balistreri, WF, Bezerra, JA. Whatever happened to “neonatal hepatitis”? Clin Liver Dis 2006;10:27–53, v.Google Scholar

Dick, MC, Mowat, AP. Hepatitis syndrome in infancy–an epidemiological survey with 10 year follow up. Arch Dis Child 1985;60:512–16.CrossRef Google Scholar

Danks, DM, Campbell, PE, Jack, I, Rogers, J, Smith, AL. Studies of the aetiology of neonatal hepatitis and biliary atresia. Arch Dis Child 1977;52:360–7.Google Scholar

Hartley, JL, Davenport, M, Kelly, DA. Biliary atresia. Lancet 2009;374:1704–13.Google Scholar

Hopkins, PC, Yazigi, N, Nylund, CM. Incidence of biliary atresia and timing of hepatoportoenterostomy in the United States. J Pediatr 2017;187:253–7.CrossRef Google Scholar PubMed

Bezerra, JA, Balistreri, WF. Cholestatic syndromes of infancy and childhood. Semin Gastrointest Dis 2001;12:54–65.Google Scholar PubMed

Torbenson, M, Hart, J, Westerhoff, M, et al. Neonatal giant cell hepatitis: histological and etiological findings. Am J Surg Pathol 2010;34:1498–503.Google Scholar

Jacquemin, E, Lykavieris, P, Chaoui, N, Hadchouel, M, Bernard, O. Transient neonatal cholestasis: origin and outcome. J Pediatr 1998;133:563–7.CrossRef Google Scholar PubMed

Emerick, KM, Whitington, PF. Molecular basis of neonatal cholestasis. Pediatr Clin North Am 2002;49:221–35.Google Scholar

Carlton, VE, Pawlikowska, L, Bull, LN. Molecular basis of intrahepatic cholestasis. Ann Med 2004;36:606–17.Google Scholar

Bull, LN, Thompson, RJ. Progressive familial intrahepatic cholestasis. Clin Liver Dis 2018;22:657–69.Google Scholar

Thompson, R, Strautnieks, S. BSEP: function and role in progressive familial intrahepatic cholestasis. Semin Liver Dis 2001;21:545–50.Google Scholar

Yehezkely-Schildkraut, V, Munichor, M, Mandel, H, et al. Nonsyndromic paucity of interlobular bile ducts: report of 10 patients. J Pediatr Gastroenterol Nutr 2003;37:546–9.Google Scholar

Balistreri, WF. Intrahepatic cholestasis. J Pediatr Gastroenterol Nutr 2002;35 (Suppl 1):S17–23.Google Scholar

Moyer, V, Freese, DK, Whitington, PF, et al. Guideline for the Evaluation of Cholestatic Jaundice in Infants: Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 2004;39:115–28.Google Scholar

Sokol, RJ, Mack, C, Narkewicz, MR, Karrer, FM. Pathogenesis and outcome of biliary atresia: current concepts. J Pediatr Gastroenterol Nutr 2003;37:4–21.CrossRef Google Scholar PubMed

Kamath, BM, Piccoli, DA. Heritable disorders of the bile ducts. Gastroenterol Clin North Am 2003;32:857–75, vi.Google Scholar

Sokol, RJ, Mack, C. Etiopathogenesis of biliary atresia. Semin Liver Dis 2001;21:517–24.CrossRef Google Scholar PubMed

Kelly, DA, McKiernan, PJ. Metabolic liver disease in the pediatric patient. Clin Liver Dis 1998;2:1–30, v.Google Scholar

Goncalves, I, Hermans, D, Chretien, D, et al. Mitochondrial respiratory chain defect: a new etiology for neonatal cholestasis and early liver insufficiency. J Hepatol 1995;23:290–4.Google Scholar

Sokol, RJ, Stall, C. Anthropometric evaluation of children with chronic liver disease. Am J Clin Nutr 1990;52:203–8.Google Scholar

Davenport, M. Biliary atresia. Semin Pediatr Surg 2005;14:42–8.Google Scholar

Butler, AE, Schreiber, RA, Yanchar, N, Emil, S, Laberge, JM. The Canadian Biliary Atresia Registry: Improving the care of Canadian infants with biliary atresia. Paediatr Child Health 2016;21:131–4.Google Scholar

Serinet, MO, Wildhaber, BE, Broue, P, et al. Impact of age at Kasai operation on its results in late childhood and adolescence: a rational basis for biliary atresia screening. Pediatrics 2009;123:1280–6.Google Scholar

Mieli-Vergani, G, Howard, ER, Portman, B, Mowat, AP. Late referral for biliary atresia–missed opportunities for effective surgery. Lancet 1989;1:421–3.Google Scholar

Lee, WS. Pre-admission consultation and late referral in infants with neonatal cholestasis. J Paediatr Child Health 2008;44:57–61.Google Scholar

Schreiber, RA, Barker, CC, Roberts, EA, et al. Biliary atresia: the Canadian experience. J Pediatr 2007;151:659–65, 65 e1.Google Scholar

Suchy, FJ. Clinical problems with developmental anomalies of the biliary tract. Semin Gastrointest Dis 2003;14:156–64.Google Scholar PubMed

Suchy, FJ. (1992). Neonatal jaundice and cholestasis. In: Kaplowitz, N. (Ed.), Liver and Biliary Diseases (p. 446). Baltimore, MD: Williams & Wilkins.Google Scholar

Rinaldo, P, Tortorelli, S, Matern, D. Recent developments and new applications of tandem mass spectrometry in newborn screening. Curr Opin Pediatr 2004;16:427–33.Google Scholar

Balistreri, WF, HH, AK, Setchell, KD, Gremse, D, Ryckman, FC, Schroeder, TJ. New methods for assessing liver function in infants and children. Ann Clin Lab Sci 1992;22:162–74.Google Scholar

Rosenthal, P. Assessing liver function and hyperbilirubinemia in the newborn. National Academy of Clinical Biochemistry. Clin Chem 1997;43:228–34.Google Scholar

Maggiore, G, Bernard, O, Hadchouel, M, Lemonnier, A, Alagille, D. Diagnostic value of serum gamma-glutamyl transpeptidase activity in liver diseases in children. J Pediatr Gastroenterol Nutr 1991;12:21–6.Google Scholar

Shneider, BL, Moore, J, Kerkar, N, et al. Initial assessment of the infant with neonatal cholestasis. Is this biliary atresia? PloS One 2017;12:e0176275.Google Scholar

Fitzpatrick, E, Jardine, R, Farrant, P, et al. Predictive value of bile duct dimensions measured by ultrasound in neonates presenting with cholestasis. J Pediatr Gastroenterol Nutr 2010;51:55–60.Google Scholar

Nievelstein, RA, Robben, SG, Blickman, JG. Hepatobiliary and pancreatic imaging in children: techniques and an overview of non-neoplastic disease entities. Pediatric Radiology 2011;41:55–75.CrossRef Google Scholar

Kanegawa, K, Akasaka, Y, Kitamura, E, et al. Sonographic diagnosis of biliary atresia in pediatric patients using the “triangular cord” sign versus gallbladder length and contraction. AJR Am J Roentgenol 2003;181:1387–90.Google Scholar

Kianifar, HR, Tehranian, S, Shojaei, P, et al. Accuracy of hepatobiliary scintigraphy for differentiation of neonatal hepatitis from biliary atresia: systematic review and meta-analysis of the literature. Pediatric Radiology 2013;43:905–19.Google Scholar

Russo, P, Magee, JC, Boitnott, J, et al. Design and validation of the biliary atresia research consortium histologic assessment system for cholestasis in infancy. Clin Gastroenterol Hepatol 2011;9(4):357–62.e2.CrossRef Google Scholar

Russo, P, Magee, JC, Anders, RA, et al. Key histopathologic features of liver biopsies that distinguish biliary atresia from other causes of infantile cholestasis and their correlation with outcome: a multicenter study. Am J Surg Pathol 2016;40:1601–15.Google Scholar

Feldman, AG, Sokol, RJ. Neonatal cholestasis: emerging molecular diagnostics and potential novel therapeutics. Nat Rev Gastroenterol Hepatol 2019;16(61):346–60.Google Scholar

Wang, NL, Lu, YL, Zhang, P, et al. A specially designed multi-gene panel facilitates genetic diagnosis in children with intrahepatic cholestasis: simultaneous test of known large insertions/deletions. PloS One 2016;11:e0164058.Google Scholar

Togawa, T, Sugiura, T, Ito, K, et al. Molecular genetic dissection and neonatal/infantile intrahepatic cholestasis using targeted next-generation sequencing. J Pediatr 2016;171:171–7 e4.Google Scholar

Karpen, S, Kamath, B, Alexander, J, et al. Use of a comprehensive 66 gene panel to diagnose the causes of cholestasis in >700 individuals. Hepatology 2017;66(S1):655A Abstract 1213.Google Scholar

Herbst, SM, Schirmer, S, Posovszky, C, et al. Taking the next step forward – Diagnosing inherited infantile cholestatic disorders with next generation sequencing. Mol Cell Probes 2015;29:291–8.Google Scholar

Lien, TH, Chang, MH, Wu, JF, et al. Effects of the infant stool color card screening program on 5-year outcome of biliary atresia in Taiwan. Hepatology 2011;53:202–8.Google Scholar

Franciscovich, A, Vaidya, D, Doyle, J, et al. PoopMD, a mobile health application, accurately identifies infant acholic stools. PloS One 2015;10:e0132270.CrossRef Google Scholar PubMed

Lertudomphonwanit, C, Mourya, R, Fei, L, et al. Large-scale proteomics identifies MMP-7 as a sentinel of epithelial injury and of biliary atresia. Sci Transl Med 2017;9:eaan8462. doi: 10.1126/scitranslmed.aan8462Google Scholar

Harpavat, S, Finegold, MJ, Karpen, SJ. Patients with biliary atresia have elevated direct/conjugated bilirubin levels shortly after birth. Pediatrics 2011;128:e1428–33.Google Scholar

Harpavat, S, Garcia-Prats, JA, Shneider, BL. Newborn bilirubin screening for biliary atresia. N Engl J Med 2016;375:605–6.Google Scholar

Harpavat, S, Ramraj, R, Finegold, MJ, et al. Newborn direct or conjugated bilirubin measurements as a potential screen for biliary atresia. J Pediatr Gastroenterol Nutr 2016;62:799–803.Google Scholar

References

Shneider, BL, Moore, J, Kerkar, N, Magee, JC, Ye, W, Karpen, SJ, Kamath, BM, et al. Initial assessment of the infant with neonatal cholestasis-Is this biliary atresia? PLoS One 2017;12:e0176275.Google Scholar

Feldman, AG, Sokol, RJ. Neonatal cholestasis: emerging molecular diagnostics and potential novel therapeutics. Nat Rev Gastroenterol Hepatol 2019;16:346–60.Google Scholar

Lane, E, Murray, KF. cholestasis, Neonatal. Pediatr Clin North Am 2017;64:621–39.CrossRef Google Scholar

Squires, JE, McKiernan, P. Molecular mechanisms in pediatric cholestasis. Gastroenterol Clin North Am 2018;47:921–37.Google Scholar

Sticova, E, Jirsa, M, Pawlowska, J. New insights in genetic cholestasis: from molecular mechanisms to clinical implications. Can J Gastroenterol Hepatol 2018;2018:2313675.Google Scholar

Li, Y, Lu, LG. Therapeutic roles of bile acid signaling in chronic liver diseases. J Clin Transl Hepatol 2018;6:425–30.Google Scholar

Jones, H, Alpini, G, Francis, H. Bile acid signaling and biliary functions. Acta Pharm Sin B 2015;5:123–8.Google Scholar

Lazaridis, KN, LaRusso, NF. Primary sclerosing cholangitis. N Engl J Med 2016;375:2501–2.Google Scholar

Deneau, M, Perito, E, Ricciuto, A, Gupta, N, Kamath, BM, Palle, S, Vitola, B, et al. Ursodeoxycholic acid therapy in pediatric primary sclerosing cholangitis: predictors of gamma glutamyltransferase normalization and favorable clinical course. J Pediatr 2019;209:92–6.Google Scholar

Cheng, K, Ashby, D, Smyth, RL. Ursodeoxycholic acid for cystic fibrosis-related liver disease. Cochrane Database Syst Rev 2017;9:CD000222.Google Scholar PubMed

Boelle, PY, Debray, D, Guillot, L, Clement, A, Corvol, H, French CF Modifier Gene Study Investigators. Cystic fibrosis liver disease: outcomes and risk factors in a large cohort of French patients. Hepatology 2019;69:1648–56.Google Scholar

Balistreri, WF. Bile acid therapy in pediatric hepatobiliary disease: the role of ursodeoxycholic acid. J Pediatr Gastroenterol Nutr 1997;24:573–89.CrossRef Google Scholar PubMed

Jacquemin, E, Hermans, D, Myara, A, Habes, D, Debray, D, Hadchouel, M, Sokal, EM, et al. Ursodeoxycholic acid therapy in pediatric patients with progressive familial intrahepatic cholestasis. Hepatology 1997;25:519–23.Google Scholar

Heubi, JE, Setchell, KD, Jha, P, Buckley, D, Zhang, W, Rosenthal, P, Potter, C, et al. Treatment of bile acid amidation defects with glycocholic acid. Hepatology 2015;61:268–74.Google Scholar

Ruutu, T, Eriksson, B, Remes, K, Juvonen, E, Volin, L, Remberger, M, Parkkali, T, et al. Ursodeoxycholic acid for the prevention of hepatic complications in allogeneic stem cell transplantation. Blood 2002;100:1977–83.Google Scholar

Bezerra, JA, Spino, C, Magee, JC, Shneider, BL, Rosenthal, P, Wang, KS, Erlichman, J, et al. Use of corticosteroids after hepatoportoenterostomy for bile drainage in infants with biliary atresia: the START randomized clinical trial. JAMA 2014;311:1750–9.Google Scholar

Chiang, JYL, Ferrell, JM. Bile acids as metabolic regulators and nutrient sensors. Annu Rev Nutr 2019;39:175–200.Google Scholar

Gitto, S, Guarneri, V, Sartini, A, Andreone, P. The use of obeticholic acid for the management of non-viral liver disease: current clinical practice and future perspectives. Expert Rev Gastroenterol Hepatol 2018;12:165–71.Google Scholar

Koyama, Y, Brenner, DA. Liver inflammation and fibrosis. J Clin Invest 2017;127:55–64.Google Scholar

Koyama, Y, Xu, J, Liu, X, Brenner, DA. New developments on the treatment of liver fibrosis. Dig Dis 2016;34:589–96.Google Scholar

Bergasa, NV. The itch of liver disease. Semin Cutan Med Surg 2011;30:93–8.Google Scholar

Thebaut, A, Debray, D, Gonzales, E. An update on the physiopathology and therapeutic management of cholestatic pruritus in children. Clin Res Hepatol Gastroenterol 2018;42:103–9.Google Scholar

Hegade, VS, Bolier, R, Oude Elferink, RP, Beuers, U, Kendrick, S, Jones, DE. A systematic approach to the management of cholestatic pruritus in primary biliary cirrhosis. Frontline Gastroenterol 2016;7:158–66.Google Scholar

Kremer, AE, van Dijk, R, Leckie, P, Schaap, FG, Kuiper, EM, Mettang, T, Reiners, KS, et al. Serum autotaxin is increased in pruritus of cholestasis, but not of other origin, and responds to therapeutic interventions. Hepatology 2012;56:1391–1400.Google Scholar

Meixiong, J, Vasavda, C, Green, D, Zheng, Q, Qi, L, Kwatra, SG, Hamilton, JP, et al. Identification of a bilirubin receptor that may mediate a component of cholestatic itch. Elife 2019;8:e44116.Google Scholar

De Vloo, C, Nevens, F. Cholestatic pruritus: an update. Acta Gastroenterol Belg 2019;82:75–82.Google Scholar

Yerushalmi, BSR, Narkewicz, MR, Smith, D, Karrer, FM. Use of rifampin for severe pruritus in children with chronic cholestasis. J Pediatr Gastroenterol Nutr 1999;29(4):442–7.Google Scholar

Wolfhagen, FH, Sternieri, E, Hop, WC, Vitale, G, Bertolotti, M, Van Buuren, HR. Oral naltrexone treatment for cholestatic pruritus: a double-blind, placebo-controlled study. Gastroenterology 1997;113:1264–9.Google Scholar

Shneider, BL, Spino, C, Kamath, BM, Magee, JC, Bass, LM, Setchell, KD, Miethke, A, et al. Placebo-controlled randomized trial of an intestinal bile salt transport inhibitor for pruritus in Alagille syndrome. Hepatol Commun 2018;2:1184–98.Google Scholar

Hegade, VS, Kendrick, SF, Dobbins, RL, Miller, SR, Thompson, D, Richards, D, Storey, J, et al. Effect of ileal bile acid transporter inhibitor GSK2330672 on pruritus in primary biliary cholangitis: a double-blind, randomised, placebo-controlled, crossover, phase 2a study. Lancet 2017;389:1114–23.Google Scholar

Bull, LN, Pawlikowska, L, Strautnieks, S, Jankowska, I, Czubkowski, P, Dodge, JL, Emerick, K, et al. Outcomes of surgical management of familial intrahepatic cholestasis 1 and bile salt export protein deficiencies. Hepatol Commun 2018;2:515–28.Google Scholar

Hegade, VS, Krawczyk, M, Kremer, AE, Kuczka, J, Gaouar, F, Kuiper, EM, van Buuren, HR, et al. The safety and efficacy of nasobiliary drainage in the treatment of refractory cholestatic pruritus: a multicentre European study. Aliment Pharmacol Ther 2016;43:294–302.Google Scholar

Austin, PW, Gerber, L, Karrar, AK. Fatigue in chronic liver disease: exploring the role of the autonomic nervous system. Liver Int 2015;35:1489–91.Google Scholar

Dyson, JK, Elsharkawy, AM, Lamb, CA, Al-Rifai, A, Newton, JL, Jones, DE, Hudson, M. Fatigue in primary sclerosing cholangitis is associated with sympathetic over-activity and increased cardiac output. Liver Int 2015;35:1633–41.Google Scholar

Black, DD. Chronic cholestasis and dyslipidemia: what is the cardiovascular risk? J Pediatr 2005;146:306–7.Google Scholar

Longo, M, Crosignani, A, Podda, M. Hyperlipidemia in chronic cholestatic liver disease. Curr Treat Options Gastroenterol 2001;4:111–14.Google Scholar

Yu, RWY, Xiao, Y, Mo, L, Liu, A, Li, D, Ge, T, Yu, G, Zhang, T. Prevalence of malnutrition and risk of undernutrition in hospitalised children with liver disease. J Nutr Sci 2017;6:e55:1–5.CrossRef Google Scholar PubMed

Chin, SE, Shepherd, RW, Thomas, BJ, Cleghorn, GJ, Patrick, MK, Wilcox, JA, Ong, TH, et al. The nature of malnutrition in children with end-stage liver disease awaiting orthotopic liver transplantation. Am J Clin Nutr 1992;56:164–8.Google Scholar

Bucuvalas, JC, Cutfield, W, Horn, J, Sperling, MA, Heubi, JE, Campaigne, B, Chernausek, SD. Resistance to the growth-promoting and metabolic effects of growth hormone in children with chronic liver disease. J Pediatr 1990;117:397–402.Google Scholar

Sokol, RJ, Stall, C. Anthropometric evaluation of children with chronic liver disease. Am J Clin Nutr 1990;52:203–8.CrossRef Google Scholar PubMed

Hogler, W, Baumann, U, Kelly, D. Growth and bone health in chronic liver disease and following liver transplantation in children. Pediatr Endocrinol Rev 2010;7:266–74.Google Scholar

Loomes, KM, Spino, C, Goodrich, NP, Hangartner, TN, Marker, AE, Heubi, JE, Kamath, BM, et al. Bone density in children with chronic liver disease correlates with growth and cholestasis. Hepatology 2019;69:245–57.Google Scholar

Mandato, C, Di Nuzzi, A, Vajro, P. Nutrition and liver disease. Nutrients 2017;10(1):9.Google Scholar

DeRusso, P, Ye, W, Shepherd, R, Haber, BA, Shneider, BL, Whitington, PF, Schwarz, KB, Bezerra, JA, et al. Growth failure and outcomes in infants with biliary atresia: a report from the Biliary Atresia Research Consortium. Hepatology 2007;46:1632–8.Google Scholar

Sullivan, JS, Sundaram, SS, Pan, Z, Sokol, RJ. Parenteral nutrition supplementation in biliary atresia patients listed for liver transplantation. Liver Transpl 2012;18:120–8.Google Scholar

Nightingale, S, Ng, VL. Optimizing nutritional management in children with chronic liver disease. Pediatr Clin North Am 2009;56:1161–83.Google Scholar

Yang, CH, Perumpail, BJ, Yoo, ER, Ahmed, A, Kerner, JA Jr. Nutritional needs and support for children with chronic liver disease. Nutrients 2017;9(10):1127.Google Scholar

Enguita, M, Razquin, N, Pamplona, R, Quiroga, J, Prieto, J, Fortes, P. The cirrhotic liver is depleted of docosahexaenoic acid (DHA), a key modulator of NF-kappaB and TGFbeta pathways in hepatic stellate cells. Cell Death Dis 2019;10:14.CrossRef Google Scholar PubMed

Sokol, RJ. Fat-soluble vitamins and their importance in patients with cholestatic liver diseases. Gastroenterol Clin North Am 1994;23:673–705.Google Scholar

Shen, YM, Wu, JF, Hsu, HY, Ni, YH, Chang, MH, Liu, YW, Lai, HS, et al. Oral absorbable fat-soluble vitamin formulation in pediatric patients with cholestasis. J Pediatr Gastroenterol Nutr 2012;55:587–91.Google Scholar

Shneider, BL, Magee, JC, Bezerra, JA, Haber, B, Karpen, SJ, Raghunathan, T, Rosenthal, P, et al. Efficacy of fat-soluble vitamin supplementation in infants with biliary atresia. Pediatrics 2012;130:e607–14.Google Scholar

Feranchak, AP, Gralla, J, King, R, Ramirez, RO, Corkill, M, Narkewicz, MR, Sokol, RJ. Comparison of indices of vitamin A status in children with chronic liver disease. Hepatology 2005;42:782–92.Google Scholar

Sathe, MN, Patel, AS. Update in pediatrics: focus on fat-soluble vitamins. Nutr Clin Pract 2010;25:340–6.Google Scholar

Sokol, RJ. Assessing vitamin E status in childhood cholestasis. J Pediatr Gastroenterol Nutr 1987;6:10–13.Google Scholar

Sokol, RJ, Heubi, JE, Butler-Simon, N, McClung, HJ, Lilly, JR, Silverman, A. Treatment of vitamin E deficiency during chronic childhood cholestasis with oral d-alpha-tocopheryl polyethylene glycol-1000 succinate. Gastroenterology 1987;93:975–85.Google Scholar

Sokol, RJ. A new old treatment for vitamin E deficiency in cholestasis. J Pediatr Gastroenterol Nutr 2016;63:577–8.Google Scholar

Sokol, RJ, Butler-Simon, N, Conner, C, Heubi, JE, Sinatra, FR, Suchy, FJ, Heyman, MB, et al. Multicenter trial of d-alpha-tocopheryl polyethylene glycol 1000 succinate for treatment of vitamin E deficiency in children with chronic cholestasis. Gastroenterology 1993;104:1727–35.Google Scholar

Haney, S, Harper, J, Truemper, E. Progressive familial intrahepatic cholestasis presenting with an intracranial bleed and mimicking abusive head trauma. WMJ 2019;118:47–8.Google Scholar

Yanofsky, RA, Jackson, VG, Lilly, JR, Stellin, G, Klingensmith, WC, 3rd, Hathaway, WE. The multiple coagulopathies of biliary atresia. Am J Hematol 1984;16:171–80.Google Scholar

Heubi, JE, Higgins, JV, Argao, EA, Sierra, RI, Specker, BL. The role of magnesium in the pathogenesis of bone disease in childhood cholestatic liver disease: a preliminary report. J Pediatr Gastroenterol Nutr 1997;25:301–6.Google Scholar

Mattar, RH, Azevedo, RA, Speridiao, PG, Fagundes Neto, U, Morais, MB. Nutritional status and intestinal iron absorption in children with chronic hepatic disease with and without cholestasis. J Pediatr 2005;81:317–24.Google Scholar

Gold, A, Rogers, A, Cruchley, E, Rankin, S, Parmar, A, Kamath, BM, Avitzur, Y, et al. Assessment of school readiness in chronic cholestatic liver disease: a pilot study examining children with and without liver transplantation. Can J Gastroenterol Hepatol 2017;2017:9873945.Google Scholar

Ng, VL, Sorensen, LG, Alonso, EM, Fredericks, EM, Ye, W, Moore, J, Karpen, SJ, et al. Neurodevelopmental outcome of young children with biliary atresia and native liver: results from the ChiLDReN Study. J Pediatr 2018;196:139–47 e133.Google Scholar

Feldman, AG, Kempe, A, Beaty, BL, Sundaram, SS. Studies of Pediatric Liver Transplantation Research Group. Immunization practices among pediatric transplant hepatologists. Pediatr Transplant 2016;20:1038–44.Google Scholar

References

Hamilton, JR, Sass-Kortsak, A. Jaundice associated with severe bacterial infection in young infants. J Pediatr 1963;63:121–32.Google Scholar

Zimmerman, HJ, Fang, M, Utili, R, et al. Jaundice due to bacterial infection. Gastroenterology 1979;77:362–74.Google Scholar

Andres, JM, Walker, WA. Effect of Escherichia coli endotoxin on the developing rat liver. I. Giant cell induction and disruption in protein metabolism. Pediatr Res 1979;13:1290–3.Google Scholar

Bolder, U, Ton-Nu, HT, Schteingart, CD, et al. Hepatocyte transport of bile acids and organic anions in endotoxemic rats: impaired uptake and secretion. Gastroenterology 1997;112:214–25.Google Scholar

Borges, MAG, DeBrito, T, Borges, JMG. Hepatic manifestations in bacterial infections of infants and children. Clinical features, biochemical data and morphologic hepatic changes. Acta Hepatogastroenterol 1972;19:328–44.Google Scholar

Lam, HS, Li, AM, Chu, WCW, et al. Mal-positioned umbilical venous catheter causing liver abscess in a preterm infant. Biol Neonate 2005;88:54–6.Google Scholar

Garcia, FJ, Nager, AL. Jaundice as an early diagnostic sign of urinary tract infection in infancy. Pediatrics 2002;109:846–51.Google Scholar

Hoarau, C, Ranivoharimina, V, Chavet- Queru, MS, et al. Congenital syphilis: update and perspectives. Sante 1999;9:38–45.Google Scholar

Herman, TE. Extensive hepatic calcification secondary to fulminant neonatal syphilitic hepatitis. Pediatr Radiol 1995;25:120–2.Google Scholar

Kumar, R, Gupta, N, Sabharwal, A. Congenital tuberculosis. Indian J Pediatr 2005;72:631–3.Google Scholar

Montoya, JG, Rosso, F. Diagnosis and management of toxoplasmosis. Clin Perinatol 2005;32:705–26.Google Scholar

Desmonts, G, Couvreur, J. Congenital toxoplasmosis. A prospective study of 378 pregnancies. N Engl J Med 1974;290:1110–16.Google Scholar

Schmidt, DR, Hogh, B, Andersen, O, et al. Treatment of infants with congenital toxoplasmosis: tolerability and plasma concentrations of sulfadiazine and pyrimethamine. Eur J Pediatr 2005;165:19–25.Google Scholar

Nicol, KK, Geisinger, KR. Congenital toxoplasmosis: diagnosis by exfoliative cytology. Diagn Cytopathol 1998;18:357–61.Google Scholar

Bellomo-Brandao, MA, Andrade, PD, Costa, SC, et al. Cytomegalovirus frequency in neonatal intrahepatic cholestasis determined by serology, histology, immunohistochemistry and PCR. World J Gastroenterol 2009;15:3411–16.Google Scholar

Laifer, SA, Ehrlich, GD, Huff, DS, et al. Congenital cytomegalovirus infection in offspring of liver transplant recipients. Clin Infect Dis 1995;20:52–5.Google Scholar

Zuppan, CW, Bui, HD, Grill, BG. Diffuse hepatic fibrosis in congenital cytomegalovirus infection. J Pediatr Gastroenterol Nutr 1986;5:489–91.Google Scholar

Watkins, JB, Sunaryo, FP, Berezin, SH. Hepatic manifestations of congenital and perinatal disease. Clin Perinatol 1981;8:467–80.Google Scholar

Weller, TH, Hanshaw, JB. Virologic and clinical observations on cytomegalic inclusion disease. N Engl J Med 1962;266:1233–44.Google Scholar

Snover, DC, Horwitz, CA. Liver disease in cytomegalovirus mononucleosis: a light microscopical and immunoperoxidase study of six cases. Hepatology 1984;3: 408–12.Google Scholar

Greenfield, C, Sinickas, V, Harrison, LC. Detection of cytomegalovirus by the polymerase chain reaction. A simple, rapid and sensitive non-radioactive method. Med J Aust 1991;154:383–5.Google Scholar

Berenberg, W, Nankervis, G. Long-term follow-up of cytomegalic inclusion disease of infancy. Pediatrics 1970;46:403–10.Google Scholar

Dressler, S, Linder, D. Noncirrhotic portal fibrosis following neonatal cytomegalic inclusion disease. J Pediatr 1978;93:887–8.Google Scholar

Thompson, C, Whitley, R. Neonatal herpes simplex virus infections: where are we now? World J Gastroenterol 2009;15:3411–16.Google Scholar

Twagira, M, Hadzic, N, Smith, M, et al. Disseminated neonatal herpes simplex virus (HSV) type 2 infection diagnosed by HSV DNA detection in blood and successfully managed by liver transplantation. Eur J Pediatr 2004;163:166–9.Google Scholar

Nakamura, Y, Yamamoto, S, Tanaka, S, et al. Herpes simplex viral infection in human neonates: an immunohistochemical and electron microscopic study. Human Pathol 1985;16:1091–7.Google Scholar

Raga, J, Chrystal, V, Coovadia, HM. Usefulness of clinical features and liver biopsy in diagnosis of disseminated herpes simplex infection. Arch Dis Child 1984;59:820–4.Google Scholar

Egawa, H, Inomata, Y, Nakayama, S, et al. Fulminant hepatic failure secondary to herpes simplex virus infection in a neonate: a case report of successful treatment with liver transplantation and perioperative acyclovir. Liver Transplant Surg 1998;4:513–15.Google Scholar

Schluter, WW, Reef, SE, Redd, SC, et al. Changing epidemiology of congenital rubella syndrome in the United States. J Infect Dis 1998;178:636–41.Google Scholar

Monif, GRG, Asofsky, R, Sever, JL. Hepatic dysfunction in the congenital rubella syndrome. BMJ 1966;1:1086–8.Google Scholar

Strauss, L, Bernstein, J. Neonatal hepatitis in congenital rubella. Arch Pathol 1968;86:317–27.Google Scholar

Duff, P. Hepatitis in pregnancy. Semin Perinatol 1998;22:277–83.Google Scholar

Noble, RC, Kane, MA, Reeves, SA, et al. Posttransfusion hepatitis A in a neonatal intensive care unit. JAMA 1984;252:2711–15.Google Scholar

Renge, RL, Dani, VS, Chitambar, SD, Arankalle, VA. Vertical transmission of hepatitis A. Indian J Pediatr 2002;69:535–6.Google Scholar

Leikin, E, Lysikiewicz, A, Garry, D, Tejani, N. Intrauterine transmission of hepatitis A virus. Obstet Gynecol 1996;88:690–1.Google Scholar

Poland, GA, Jacobson, RM. Prevention of hepatitis B with the hepatitis B vaccine. N Eng J Med 2004;351:2832–8.Google Scholar

Tang, JR, Hsu, HY, Lin, HH, et al. Hepatitis B surface antigenemia at birth: a long-term follow-up study. J Pediatr 1998;133:374–7.Google Scholar

Suskind, DL, Rosenthal, P. Chronic viral hepatitis. Adolesc Med Clin 2004;15:145–58.Google Scholar

Granovsky, MO, Minkoff, HL, Tess, BH, et al. Hepatitis C virus infection in the mothers and infants cohort study. Pediatrics 1998;102:355–9.Google Scholar

Kumar, RM, Shahul, S. Role of breast-feeding in transmission of hepatitis C virus to infants of HCV-infected mothers. J Hepatol 1998;29:191–7.Google Scholar

Chang, MH. Chronic hepatitis virus infection in children. J Gastroenterol Hepatol 1998;13:541–8.Google Scholar

Realdi, G, Alberti, A, Rugge, M, et al. Long-term follow-up of acute and chronic non-A, non-B post-transfusion hepatitis: evidence of progression to liver cirrhosis. Gut 1982;23:270–5.Google Scholar

Hasan, F, Jeffers, LJ, De Medina, M, et al. Hepatitis-C associated hepatocellular carcinoma. Hepatology 1990;12:589–91.Google Scholar

McHutchison, JG, Gordon, SC, Schiff, ER, et al. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N Engl J Med 1998;339:1485–92.Google Scholar PubMed

Fried, MW, Shiffman, ML, Reddy, KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002;347:975–82.Google Scholar

Gonzalez-Peralta, RP. Treatment of chronic hepatitis C in children. Pediatr Transplant 2004;8:639–43.Google Scholar

Bortolotti, F, Iorio, R, Nebbia, G, et al. Interferon treatment in children with chronic hepatitis C: long-lasting remission in responders, and risk for disease progression in non-responders. Dig Liver Dis 2005;37:336–41.Google Scholar

Schwarz, KB, Gonzalez-Peralta, RP, Murray, KF, et al. The combination of ribavirin and peginterferon is superior to peginterferon and placebo for children and adolescents with chronic hepatitis C. Gastroenterology 2011;140:450–8.Google Scholar

Terrault, NA, Lok, ASF, McMahon, BJ, chang, KM, Hwang, JP, Jonas, MM, Brown, RS Jr., et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology 2018;67:1560–99.Google Scholar

Chen, HL, Chang, MH, Lin, HH, et al. Antibodies to E2 protein of hepatitis G virus in children: different responses according to age at infection. J Pediatr 1998;133:382–5.Google Scholar

Zanetti, AR, Tanzi, E, Romano, L, et al. Multicenter trial on mother-to-infant transmission of GBV-C virus. The Lombardy Study Group on Vertical/Perinatal Hepatitis Viruses Transmission. J Med Virol 1998;54:107–12.Google Scholar

Woelfle, J, Berg, T, Keller, KM, et al. Persistent hepatitis G virus infection after neonatal transfusion. J Pediatr Gastroenterol Nutr 1998;26:402–7.Google Scholar

Naoumov, NV, Petrova, EP, Thomas, MG, et al. Presence of a newly described human DNA virus (TTV) in patients with liver disease. Lancet 1998;352:195–7.Google Scholar

Okamoto, H, Akahane, Y, Ukita, M, et al. Fecal excretion of a nonenveloped DNA virus (TTV) associated with posttransfusion non-A-G hepatitis. J Med Virol 1998;56:128–32.Google Scholar

Koidl, C, Michael, B, Berg, J, et al. Detection of transfusion transmitted virus DNA by real-time PCR. J Clin Virol 2004;29:277–81.Google Scholar

Abzug, MJ. Prognosis for neonates with enterovirus hepatitis and coagulopathy. Pediatr Infect Dis J 2001;20:758–63.Google Scholar PubMed

Kawashima, H, Ryou, S, Nishimata, S, et al. Enteroviral hepatitis in children. Pediatr Int 2004;46:130–4.Google Scholar

Abzug, MJ. Presentation, diagnosis, and management of enterovirus infections in neonates. Paediatr Drugs 2004;6:1–10.Google Scholar

Pardi, DS, Romero, Y, Mertz, LE, et al. Hepatitis-associated aplastic anemia and acute parvovirus B19 infection: a report of two cases and a review of the literature. Am J Gastroenterol 1998;93:468–70.Google Scholar

Granot, E, Miskin, H, Aker, M. Monoclonal anti-CD52 antibodies: a potential mode of therapy for parvovirus B19 hepatitis. Transplant Proc 2001;33:2151–3.Google Scholar

Tajiri, H, Tanaka-Taya, K, Ozaki, Y, et al. Chronic hepatitis in an infant, in association with human herpesvirus-6 infection. J Pediatr 1997;131:473–5.Google Scholar

Landing, BH. Considerations of the pathogenesis of neonatal hepatitis, biliary atresia and choledochal cyst: the concept of infantile obstructive cholangiopathy. Prog Pediatr Surg 1974;4:113–39.Google Scholar

Steele, MI, Marshall, CM, Lloyd, RE, et al. Reovirus 3 not detected by reverse transcriptase-mediated polymerase chain reaction analysis of preserved tissue from infants with cholestatic liver disease. Hepatology 1995;21:697–702.Google Scholar

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;27:1475–82.Google Scholar

Phillips, MJ, Blendis, LM, Poucell, S, et al. Syncytial giant-cell hepatitis: sporadic hepatitis with distinctive pathological features, a severe clinical course, and paramyxoviral features. N Engl J Med 1991;324:455–60.Google Scholar

Kahn, E, Greco, MA, Daum, F, et al. Hepatic pathology in pediatric acquired immunodeficiency syndrome. Human Pathol 1991;22:1111–19.Google Scholar

Poles, MA, Dieterich, DT, Schwarz, ED, et al. Liver biopsy findings in 501 patients infected with human immunodeficiency virus (HIV). J AIDS Hum Retrovirol 1996;11:170–7.Google Scholar

Dworsky, M, Whitley, R, Alford, C. Herpes zoster in early infancy. Am J Dis Child 1980;134:618–19.Google Scholar

Costello, A, Dua, T, Duran, P, Gulmezoglu, M, Oladapo, OT, Perea, W, Pires, J, et al. Defining the syndrome associated with congenital Zika virus infection. Bull World Health Organ 2016;94:406–6A.Google Scholar

Rice, ME, Galang, RR, Roth, NM, Ellington, SR, Moore, CA, Valencia-Prado, M, Ellis, EM, et al. Vital signs: Zika-associated birth defects and neurodevelopmental abnormalities possibly associated with congenital Zika virus infection – U.S. Territories and Freely Associated States, 2018. MMWR Morb Mortal Wkly Rep 2018;67:858–67.Google Scholar

Moore, CA, Staples, JE, Dobyns, WB, Pessoa, A, Ventura, CV, Fonseca, EB, Ribeiro, EM, et al. Characterizing the pattern of anomalies in congenital Zika syndrome for pediatric clinicians. JAMA Pediatr 2017;171:288–95.Google Scholar

Wu, Y, Cui, X, Wu, N, Song, R, Yang, W, Zhang, W, Fan, D, et al. A unique case of human Zika virus infection in association with severe liver injury and coagulation disorders. Sci Rep 2017;7:11393.Google Scholar

Adebanjo, T, Godfred-Cato, S, Viens, L, Fischer, M, Staples, JE, Kuhnert-Tallman, W, Walke, H, et al. Update: Interim Guidance for the Diagnosis, Evaluation, and Management of Infants with Possible Congenital Zika Virus Infection – United States, October 2017. MMWR Morb Mortal Wkly Rep 2017;66:1089–99.Google Scholar

Fleming-Dutra, KE, Nelson, JM, Fischer, M, Staples, JE, Karwowski, MP, Mead, P, Villanueva, J, et al. Update: Interim Guidelines for Health Care Providers Caring for Infants and Children with Possible Zika Virus Infection–United States, February 2016. MMWR Morb Mortal Wkly Rep 2016;65:182–7.Google Scholar

Laxer, RM, Roberts, EA, Gross, KR, et al. Liver disease in neonatal lupus erythematosus. J Pediatr 1990;116:238–42.Google Scholar

Lee, LA, Sokol, RJ, Buyon, JP. Hepatobiliary disease in neonatal lupus: prevalence and clinical characteristics in cases enrolled in a national registry. Pediatrics 2002;109:E11.Google Scholar

Alpert, LI, Strauss, L, Hirschhorn, K. Neonatal hepatitis and biliary atresia associated with trisomy 17–18 syndrome. N Engl J Med 1969;280:16–20.Google Scholar

Schwab, M, Niemeyer, C, Schwarzer, U. Down syndrome, transient myeloproliferative disorder, and infantile liver fibrosis. Med Pediatr Oncol 1998;31:159–65.Google Scholar

Pratt, DS. Cholestasis and cholestatic syndromes. Curr Opin Gastroenterol 2005;21:270–4.Google Scholar

van Mil, SW, Houwen, RH, Klomp, LW. Genetics of familial intrahepatic cholestasis syndromes. J Med Genet 2005;42:449–63.Google Scholar

Krantz, ID, Piccoli, DA, Spinner, NB. Alagille syndrome. J Med Genet 1997;34:152–7.Google Scholar

Bull, LN, van Eijk, MJ, Pawlikowska, L, et al. A gene encoding a P-type ATPase mutated in two forms of hereditary cholestasis. Nat Genet 1998;18:219–24.Google Scholar

Vivarelli, R, Grosso, S, Cioni, M, et al. Pseudo-TORCH syndrome or Baraitser–Reardon syndrome: diagnostic criteria. Brain Dev 2001;23:18–23.Google Scholar

Sanchis, A, Cervero, L, Bataller, A, et al. Genetic syndromes mimic congenital infections. J Pediatr 2005;146:701–5.Google Scholar

Knoblauch, H, Tyennstedt, C, Brueck, W, et al. Two brothers with findings resembling congenital intrauterine infection-like syndrome (pseudo-TORCH syndrome). Am J Med Genet A 2003;120:261–5.Google Scholar

Hadzic, N, Portmann, B, Lewis, I, Mieli-Vergani, G. Coombs positive giant cell hepatitis: a new feature of Evans’ syndrome. Arch Dis Child 1998;78:397–8.Google Scholar

Akylidiz, M, Karasu, Z, Arikan, C, et al. Successful liver transplantation for giant cell hepatitis and Coombs-positive haemolytic anemia: a case report. Pediatr Transplant 2005;9:630–3.Google Scholar

Balistreri, WF, Grand, R, Hoofnagle, JH, et al. Biliary atresia: current concepts and research directions. Summary of a symposium. Hepatology 1996;23:1682–92.Google Scholar

Bates, MD, Bucuvalas, JC, Alonso, MH, et al. Biliary atresia: pathogenesis and treatment. Semin Liver Dis 1998;18:281–93.Google Scholar

Tazawa, Y, Abukawa, D, Maisawa, S, et al. Idiopathic neonatal hepatitis presenting as neonatal hepatic siderosis and steatosis. Dig Dis Sci 1998;43:392–6.CrossRef Google Scholar PubMed

Shet, TM, Kandalkar, BM, Vora, IM. Neonatal hepatitis: an autopsy study of 14 cases. Indian J Pathol Microbiol 1998;41:77–84.Google Scholar

Nishinomiya, F, Abukawa, D, Takada, G, et al. Relationships between clinical and histological profiles of non-familial idiopathic neonatal hepatitis. Acta Paediatr Jpn 1996;38:242–7.Google Scholar

Ruebner, B, Thaler, MM (1979). Giant-cell transformation in infantile liver disease. In Javitt, NB (Ed.) Neonatal Hepatitis and Biliary Atresia (pp. 299–314).Bethesda, MD: US Department of Health, Education and Welfare.Google Scholar

Park, WH, Kim, SP, Park, KK, et al. Electron microscopic study of the liver with biliary atresia and neonatal hepatitis. J Pediatr Surg 1996;31:367–74.Google Scholar

Moore, L, Bourne, AJ, Moore, DJ, et al. Hepatocellular carcinoma following neonatal hepatitis. Pediatr Pathol Lab Med 1997;17:601–10.CrossRef Google Scholar PubMed

Suita, S, Arima, T, Ishii, K, et al. Fate of infants with neonatal hepatitis: pediatric surgeons’ dilemma. J Pediatr Surg 1992;27:696–9.Google Scholar

Dick, MC, Mowat, AP. Hepatitis syndrome in infancy: an epidemiological survey with 10 year follow-up. Arch Dis Child 1985;60:512–16.Google Scholar

Lee, PI, Chang, MH, Chen, DS, et al. Prognostic implications of serum alpha-fetoprotein levels in neonatal hepatitis. J Pediatr Gastroenterol Nutr 1990;11:27–31.Google Scholar

Chang, MH, Hsu, HC, Lee, CY, et al. Neonatal hepatitis: a follow-up study. J Pediatr Gastroenterol Nutr 1987;6:203–7.Google Scholar

Deutsch, J, Smith, AL, Danks, DM, et al. Long-term prognosis for babies with neonatal liver disease. Arch Dis Child 1985;60:447–51.Google Scholar

References

Desmet, VJ. Congenital diseases of intrahepatic bile ducts: variations on the theme “ductal plate malformation.” Hepatology 1992;16:1069–83.Google Scholar

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;121:4244–56.Google Scholar

Bezerra, JA, Wells, RG, Mack, CL, et al. Biliary atresia: clinical and research challenges for the 21st century. Hepatology 2018;68(3):1163–73.Google Scholar

Landing, BH, Wells, TR, Ramicone, E. Time course of the intrahepatic lesion of extrahepatic biliary atresia: a morphometric study. Pediatr Pathol 1985;4:309–19.Google Scholar

Balistreri, WF, Grand, R, Hoofnagle, JH, et al. Biliary atresia: current concepts and research directions. Summary of a symposium. Hepatology 1996;23:1682–92.Google Scholar

Bessho, K, Bezerra, JA. Biliary atresia: will blocking inflammation tame the disease? Annu Rev Med 2011;62:171–85.Google Scholar

Bezerra, JA, Tiao, G, Ryckman, FC, et al. Genetic induction of proinflammatory immunity in children with biliary atresia. Lancet 2002;360:1653–9.Google Scholar

Mack, CL, Tucker, RM, Sokol, RJ, et al. Biliary atresia is associated with CD4+ Th1 cell-mediated portal tract inflammation. Pediatr Res 2004;56:79–87.Google Scholar

Yoon, PW, Bresee, JS, Olney, RS, et al. Epidemiology of biliary atresia: a population-based study. Pediatrics 1997;99:376–82.Google Scholar

Davenport, M, Savage, M, Mowat, AP, et al. Biliary atresia splenic malformation syndrome: an etiologic and prognostic subgroup. Surgery 1993;113:662–8.Google Scholar

Balistreri, WF. Neonatal cholestasis. J Pediatr 1985;106:171–84.Google Scholar

Pacheco, MC, Campbell, KM, Bove, KE. Ductal plate malformation-like arrays in early explants after a Kasai procedure are independent of splenic malformation complex (heterotaxy). Pediatr Dev Pathol 2009;12:355–60.Google Scholar

Davenport, M, Caponcelli, E, Livesey, E, et al. Surgical outcome in biliary atresia: etiology affects the influence of age at surgery. Ann Surg 2008;247:694–8.Google Scholar

Hsiao, CH, Chang, MH, Chen, HL, et al. Universal screening for biliary atresia using an infant stool color card in Taiwan. Hepatology 2008;47:1233–40.Google Scholar

Fischler, B, Ehrnst, A, Forsgren, M, et al. The viral association of neonatal cholestasis in Sweden: a possible link between cytomegalovirus infection and extrahepatic biliary atresia. J Pediatr Gastroenterol Nutr 1998;27:57–64.Google Scholar

Jevon, GP, Dimmick, JE. Biliary atresia and cytomegalovirus infection: a DNA study. Pediatr Dev Pathol 1999;2:11–14.Google Scholar

Mason, AL, Xu, L, Guo, L, et al. Detection of retroviral antibodies in primary biliary cirrhosis and other idiopathic biliary disorders. Lancet 1998;351:1620–4.Google Scholar

Mack, CL. The pathogenesis of biliary atresia: evidence for a virus-induced autoimmune disease. Semin Liver Dis 2007;27:233–42.Google Scholar

Szavay, PO, Leonhardt, J, Czech-Schmidt, G, et al. The role of reovirus type 3 infection in an established murine model for biliary atresia. Eur J Pediatr Surg 2002;12:248–50.Google Scholar

Riepenhoff-Talty, M, Schaekel, K, Clark, HF, et al. Group A rotaviruses produce extrahepatic biliary obstruction in orally inoculated newborn mice. Pediatr Res 1993;33:394–9.Google Scholar

Riepenhoff-Talty, M, Gouvea, V, Evans, MJ, et al. Detection of group C rotavirus in infants with extrahepatic biliary atresia. J Infect Dis 1996;174:8–15.Google Scholar

Lin, YC, Chang, MH, Liao, SF, et al. Decreasing rate of biliary atresia in Taiwan: a survey, 2004–2009. Pediatrics 2011;128:e530–6.Google Scholar

Tan, CE, Davenport, M, Driver, M, et al. Does the morphology of the extrahepatic biliary remnants in biliary atresia influence survival? A review of 205 cases. J Pediatr Surg 1994;29:1459–64.Google Scholar

Sokol, RJ, Shepherd, RW, Superina, R, et al. Screening and outcomes in biliary atresia: summary of a National Institutes of Health workshop. Hepatology 2007;46:566–81.Google Scholar

Schon, 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;110:157–65.Google Scholar

Desmet, VJ. Intrahepatic bile ducts under the lens. J Hepatol 1985;1:545–59.Google Scholar

Silveira, TR, Salzano, FM, Donaldson, PT, et al. Association between HLA and extrahepatic biliary atresia. J Pediatr Gastroenterol Nutr 1993;16:114–17.Google Scholar

Cheng, G, Tang, CS, Wong, EH, et al. Common genetic variants regulating ADD3 gene expression alter biliary atresia risk. J Hepatol 2013;59:1285–91.Google Scholar

Moyer, K, Kaimal, V, Pacheco, C, et al. Staging of biliary atresia at diagnosis by molecular profiling of the liver. Genome Med 2010;2:33.Google Scholar

Mack, CL, Falta, MT, Sullivan, AK, et al. Oligoclonal expansions of CD4+ and CD8+ T-cells in the target organ of patients with biliary atresia. Gastroenterology 2007;133:278–87.Google Scholar

Lu, BR, Brindley, SM, Tucker, RM, et al. Alpha-enolase autoantibodies cross-reactive to viral proteins in a mouse model of biliary atresia. Gastroenterology 2010;139:1753–61.Google Scholar

Jafri, M, Donnelly, B, Allen, S, et al. Cholangiocyte expression of alpha2beta1-integrin confers susceptibility to rotavirus-induced experimental biliary atresia. Am J Physiol Gastrointest Liver Physiol 2008;295:G16–G26.Google Scholar

Saxena, V, Shivakumar, P, Sabla, G, et al. Dendritic cells regulate natural killer cell activation and epithelial injury in experimental biliary atresia. Sci Transl Med 2011;3:102ra94.Google Scholar

Miethke, AG, Saxena, V, Shivakumar, P, et al. Post-natal paucity of regulatory T cells and control of NK cell activation in experimental biliary atresia. J Hepatol 2010;52:718–26.Google Scholar

Harper, P, Plant, JW, Unger, DB. Congenital biliary atresia and jaundice in lambs and calves. Aust Vet J 1990;67:18–22.Google Scholar

Klippel, CH. A new theory of biliary atresia. J Pediatr Surg 1972;7:651–4.Google Scholar

Choi, SO, Park, WH, Lee, HJ, et al. “Triangular cord”: a sonographic finding applicable in the diagnosis of biliary atresia. J Pediatr Surg 1996;31:363–6.Google Scholar

Alagille, D. Cholestasis in the first three months of life. Prog Liver Dis 1979;6:471–85.Google Scholar

Zerbini, MC, Gallucci, SD, Maezono, R, et al. Liver biopsy in neonatal cholestasis: a review on statistical grounds. Mod Pathol 1997;10:793–9.Google Scholar

Markowitz, J, Daum, F, Kahn, EI, et al. Arteriohepatic dysplasia. I. Pitfalls in diagnosis and management. Hepatology 1983;3:74–6.Google Scholar

Kasai, M, Watanabe, I, Ohi, R. Follow-up studies of long-term survivors after hepatic portoenterostomy for “noncorrectible” biliary atresia. J Pediatr Surg 1975;10:173–82.Google Scholar

Endo, M, Katsumata, K, Yokoyama, J, et al. Extended dissection of the porta hepatis and creation of an intussuscepted ileocolic conduit for biliary atresia. J Pediatr Surg 1983;18:784–93.Google Scholar

Hashimoto, T, Otobe, Y, Shimizu, Y, et al. A modification of hepatic portoenterostomy (Kasai operation) for biliary atresia. J Am Coll Surg 1997;185:548–53.Google Scholar

Ohi, R, Ibrahim, M. Biliary atresia. Semin Pediatr Surg 1992;1:115–24.Google Scholar

Ryckman, FC, Alonso, MH, Bucuvalas, JC, et al. Biliary atresia–surgical management and treatment options as they relate to outcome. Liver Transpl Surg 1998;4:S24–33.Google Scholar

Ryckman, F, Fisher, R, Pedersen, S, et al. Improved survival in biliary atresia patients in the present era of liver transplantation. J Pediatr Surg 1993;28:382–5; discussion 386.Google Scholar

Lally, KP, Kanegaye, J, Matsumura, M, et al. Perioperative factors affecting the outcome following repair of biliary atresia. Pediatrics 1989;83:723–6.Google Scholar

Chandra, RS, Altman, RP. Ductal remnants in extrahepatic biliary atresia: a histopathologic study with clinical correlation. J Pediatr 1978;93:196–200.Google Scholar

Ohya, T, Miyano, T, Kimura, K. Indication for portoenterostomy based on 103 patients with Suruga II modification. J Pediatr Surg 1990;25:801–4.Google Scholar

Davenport, M, De Ville de Goyet, J, Stringer, MD, et al. Seamless management of biliary atresia in England and Wales (1999–2002). Lancet 2004;363:1354–7.Google Scholar

Gottrand, F, Bernard, O, Hadchouel, M, et al. Late cholangitis after successful surgical repair of biliary atresia. Am J Dis Child 1991;145:213–15.Google Scholar

Lunzmann, K, Schweizer, P. The influence of cholangitis on the prognosis of extrahepatic biliary atresia. Eur J Pediatr Surg 1999;9:19–23.Google Scholar

Ohi, R, Hanamatsu, M, Mochizuki, I, et al. Reoperation in patients with biliary atresia. J Pediatr Surg 1985;20:256–9.Google Scholar

Balistreri, WF. Bile acid therapy in pediatric hepatobiliary disease: the role of ursodeoxycholic acid. J Pediatr Gastroenterol Nutr 1997;24:573–89.Google Scholar

Bezerra, JA, Spino, C, Magee, JC, et al. Use of corticosteroids after hepatoportoenterostomy for bile drainage in infants with biliary atresia: the START randomized clinical trial. JAMA 2014;311:1750–9.Google Scholar

Davenport, M, Parsons, C, Tizzard, S, et al. Steroids in biliary atresia: single surgeon, single centre, prospective study. J Hepatol 2013;59:1054–8.Google Scholar

Miga, D, Sokol, RJ, Mackenzie, T, et al. Survival after first esophageal variceal hemorrhage in patients with biliary atresia. J Pediatr 2001;139:291–6.Google Scholar

Laurent, J, Gauthier, F, Bernard, O, et al. Long-term outcome after surgery for biliary atresia. Study of 40 patients surviving for more than 10 years. Gastroenterology 1990;99:1793–7.Google Scholar

Ryckman, FC, Fisher, RA, Pedersen, SH, et al. Liver transplantation in children. Semin Pediatr Surg 1992;1:162–72.Google Scholar

Ryckman, FC, Flake, AW, Fisher, RA, et al. Segmental orthotopic hepatic transplantation as a means to improve patient survival and diminish waiting-list mortality. J Pediatr Surg 1991;26:422–7; discussion 427–8.Google Scholar

Tiao, GM, Alonso, M, Bezerra, J, et al. Liver transplantation in children younger than 1 year–the Cincinnati experience. J Pediatr Surg 2005;40:268–73.Google Scholar

Chardot, C, Carton, M, Spire-Bendelac, N, et al. Prognosis of biliary atresia in the era of liver transplantation: French national study from 1986 to 1996. Hepatology 1999;30:606–11.Google Scholar

De Matos, V, Erlichman, J, Russo, PA, et al. Does “cystic” biliary atresia represent a distinct clinical and etiological subgroup? A series of three cases. Pediatr Dev Pathol 2005;8:725–31.Google Scholar

Ando, K, Miyano, T, Kohno, S, et al. Spontaneous perforation of choledochal cyst: a study of 13 cases. Eur J Pediatr Surg 1998;8:23–5.Google Scholar

Redkar, R, Davenport, M, Howard, ER. Antenatal diagnosis of congenital anomalies of the biliary tract. J Pediatr Surg 1998;33:700–4.Google Scholar

Haller, JO, Condon, VR, Berdon, WE, et al. Spontaneous perforation of the common bile duct in children. Radiology 1989;172:621–4.Google Scholar

So, SK, Lindahl, JA, Sharp, HL, et al. Bile ascites during infancy: diagnosis using Disofenin Tc 99 m sequential scintiphotography. Pediatrics 1983;71:402–5.Google Scholar

References

Gourley, G. (2007). Neonatal jaundice and disorders of bilirubin metabolism. In: Suchy, FJSR, Balistreri, WF, (Eds.). Liver Disease in Children, 3rd Edn. (pp. 270–309). New York: Cambridge University Press.Google Scholar

Weiss, JS, Gautam, A, Lauff, JJ, Sundberg, MW, Jatlow, P, Boyer, JL, et al. The clinical importance of a protein-bound fraction of serum bilirubin in patients with hyperbilirubinemia. N Engl J Med 1983;309(3):147–50.Google Scholar

Billing, B. (1986). Intestinal and renal metabolism of bilirubin including enterohepatic circulation. In: Ostrow, JD, (Ed.). Bile Pigments and Jaundice (pp. 255–69). New York: Marcel Dekker.Google Scholar

Poland, RL, Odell, GB. Physiologic jaundice: the enterohepatic circulation of bilirubin. N Engl J Med 1971;284(1):1–6.Google Scholar

Lester, R, Schmid, R. Intestinal absorption of bile pigments. I. The enterohepatic circulation of bilirubin in the rat. J Clin Invest 1963;42:736–46.Google Scholar

Gourley, GR, Arend, RA. Beta-glucuronidase and hyperbilirubinaemia in breast-fed and formula-fed babies. Lancet. 1986;1(8482):644–6.Google Scholar

Gourley, G. (1998). Pathophysiology of breastmilk jaundice. In: Polin, R, Fox, WW, (Eds.). Fetal and Neonatal Physiology, 2nd Edn. (pp. 1499–505). Philadelphia: Saunders.Google Scholar

Gourley, GR, Li, Z, Kreamer, BL, Kosorok, MR. A controlled, randomized, double-blind trial of prophylaxis against jaundice among breastfed newborns. Pediatrics 2005;116(2):385–91.Google Scholar

Maisels, MJ, Bhutani, VK, Bogen, D, Newman, TB, Stark, AR, Watchko, JF. Hyperbilirubinemia in the newborn infant > or =35 weeks’ gestation: an update with clarifications. Pediatrics 2009;124(4):1193–8.Google Scholar

Kramer, LI. Advancement of dermal icterus in the jaundiced newborn. Am J Dis Child 1969;118(3):454–8.Google Scholar

Fujiwara, R, Chen, S, Karin, M, Tukey, RH. Reduced expression of UGT1A1 in intestines of humanized UGT1 mice via inactivation of NF-kappaB leads to hyperbilirubinemia. Gastroenterology 2012;142(1):109–18 e2.Google Scholar

American Academy of Pediatrics. Practice parameter: management of hyperbilirubinemia in the healthy term newborn. Provisional Committee for Quality Improvement and Subcommittee on Hyperbilirubinemia. Pediatrics 1994;94(4 Pt 1):558–65.Google Scholar

American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004;114(1):297–316.Google Scholar

Davis, AR, Rosenthal, P, Escobar, GJ, Newman, TB. Interpreting conjugated bilirubin levels in newborns. J Pediatr 2011;158(4):562–5 e1.Google Scholar

Harpavat, S, Garcia-Prats, JA, Shneider, BL. Newborn bilirubin screening for biliary atresia. N Engl J Med 2016;375(6):605–6.Google Scholar

Kreamer, BL, Siegel, FL, Gourley, GR. A novel inhibitor of beta-glucuronidase: L-aspartic acid. Pediatr Res 2001;50(4):460–6.Google Scholar

Odell, GB. Studies in kernicterus. I. The protein binding of bilirubin. J Clin Invest 1959;38(5):823–33.Google Scholar

Maisels, MJ, Watchko, JF, Bhutani, VK, Stevenson, DK. An approach to the management of hyperbilirubinemia in the preterm infant less than 35 weeks of gestation. J Perinatol 2012;32(9):660–4.Google Scholar

Stevenson, DK, Maisels, MJ, Watchko, J. (2012). Care of the Jaundiced Neonate. New York: McGraw-Hill Medical.Google Scholar

Kawade, N, Onishi, S. The prenatal and postnatal development of UDP-glucuronyltransferase activity towards bilirubin and the effect of premature birth on this activity in the human liver. Biochem J 1981;196(1):257–60.Google Scholar

Watchko, JF, Oski, FA. Kernicterus in preterm newborns: past, present, and future. Pediatrics 1992;90(5):707–15.Google Scholar

Watchko, JF, Maisels, MJ. The enigma of low bilirubin kernicterus in premature infants: why does it still occur, and is it preventable? Semin Perinatol 2014;38(7):397–406.Google Scholar

Rubboli, G, Ronchi, F, Cecchi, P, Rizzi, R, Gardella, E, Meletti, S, et al. A neurophysiological study in children and adolescents with Crigler-Najjar syndrome type I. Neuropediatrics 1997;28(5):281–6.Google Scholar

Odell, GB. The dissociation of bilirubin from albumin and its clinical implications. J Pediatr 1959;55:268–79.Google Scholar

McDonagh, AF PL, Lightner, DA. Phototherapy for neonatal jaundice: stereospecific and regioselective photoisomerization of bilirubin bound to human serum albumin and NMR characterization of intramolecular cyclized photoproducts. JACS 1982;(104):6867–9.Google Scholar

Steiner, LA, Bizzarro, MJ, Ehrenkranz, RA, Gallagher, PG. A decline in the frequency of neonatal exchange transfusions and its effect on exchange-related morbidity and mortality. Pediatrics 2007;120(1):27–32.Google Scholar

Maisels, MJ, McDonagh, AF. Phototherapy for neonatal jaundice. N Engl J Med 2008;358(9):920–8.Google Scholar

Yeo, KL, Perlman, M, Hao, Y, Mullaney, P. Outcomes of extremely premature infants related to their peak serum bilirubin concentrations and exposure to phototherapy. Pediatrics 1998;102(6):1426–31.Google Scholar

Morris, BH, Oh, W, Tyson, JE, Stevenson, DK, Phelps, DL, O’Shea, TM, et al. Aggressive vs. conservative phototherapy for infants with extremely low birth weight. N Engl J Med 2008;359(18):1885–96.Google Scholar

Alpay, F, Sarici, SU, Okutan, V, Erdem, G, Ozcan, O, Gokcay, E. High-dose intravenous immunoglobulin therapy in neonatal immune haemolytic jaundice. Acta Paediatr 1999;88(2):216–19.Google Scholar

Valaes, TN, Harvey-Wilkes, K. Pharmacologic approaches to the prevention and treatment of neonatal hyperbilirubinemia. Clin Perinatol 1990;17(2):245–73.Google Scholar

Gilbert, A, Lereboullet, P. La cholemie simple familiale. La Semaine Medicale 1901;21:241–3.Google Scholar

Bosma, P, Chowdhury, JR, Jansen, PH. Genetic inheritance of Gilbert’s syndrome. Lancet. 1995;346(8970):314–15.Google Scholar

Odell, GB. (1980). The Estrogenation of the Newborn. Neonatal Hyperbilirubinemia (pp. 39–41). New York: Grune and Stratton.Google Scholar

Bancroft, JD, Kreamer, B, Gourley, GR. Gilbert syndrome accelerates development of neonatal jaundice. J Pediatr 1998;132(4):656–60.Google Scholar

Kaplan, M, Renbaum, P, Levy-Lahad, E, Hammerman, C, Lahad, A, Beutler, E. Gilbert syndrome and glucose-6-phosphate dehydrogenase deficiency: a dose-dependent genetic interaction crucial to neonatal hyperbilirubinemia. Proc Natl Acad Sci U S A 1997;94(22):12128–32.Google Scholar

Debinski, HS, Lee, CS, Dhillon, AP, Mackenzie, P, Rhode, J, Desmond, PV. UDP-glucuronosyltransferase in Gilbert’s syndrome. Pathology 1996;28(3):238–41.Google Scholar

Bosma, PJ, Chowdhury, JR, Bakker, C, Gantla, S, de Boer, A, Oostra, BA, et al. The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert’s syndrome. N Engl J Med 1995;333(18):1171–5.Google Scholar

Akaba, K, Kimura, T, Sasaki, A, Tanabe, S, Wakabayashi, T, Hiroi, M, et al. Neonatal hyperbilirubinemia and a common mutation of the bilirubin uridine diphosphate-glucuronosyltransferase gene in Japanese. J Hum Genet 1999;44(1):22–5.Google Scholar

Moyer, AM, Skierka, JM, Kotzer, KE, Kluge, ML, Black, JL, Baudhuin, LM. Clinical UGT1A1 genetic analysis in pediatric patients: experience of a reference laboratory. Mol Diagn Ther 2017;21(3):327–35.Google Scholar

Skierka, JM, Kotzer, KE, Lagerstedt, SA, O’Kane, DJ, Baudhuin, LM. UGT1A1 genetic analysis as a diagnostic aid for individuals with unconjugated hyperbilirubinemia.J Pediatr 2013;162(6):1146–52, 52 e1–2.Google Scholar

Crigler, JF Jr., Najjar, VA. Congenital familial nonhemolytic jaundice with kernicterus. Pediatrics 1952;10(2):169–80.Google Scholar

Gourley, GR. Bilirubin metabolism and kernicterus. Adv Pediatr 1997;44:173–229.Google Scholar

Shevell, MI, Majnemer, A, Schiff, D. Neurologic perspectives of Crigler-Najjar syndrome type I. J Child Neurol 1998;13(6):265–9.Google Scholar

Strauss, KA, Robinson, DL, Vreman, HJ, Puffenberger, EG, Hart, G, Morton, DH. Management of hyperbilirubinemia and prevention of kernicterus in 20 patients with Crigler-Najjar disease. Eur J Pediatr 2006;165(5):306–19.Google Scholar

Arias, IM, Gartner, LM, Cohen, M, Ezzer, JB, Levi, AJ. Chronic nonhemolytic unconjugated hyperbilirubinemia with glucuronyl transferase deficiency. Clinical, biochemical, pharmacologic and genetic evidence for heterogeneity. Am J Med 1969;47(3):395–409.Google Scholar

Clarke, DJ, Moghrabi, N, Monaghan, G, Cassidy, A, Boxer, M, Hume, R, et al. Genetic defects of the UDP-glucuronosyltransferase-1 (UGT1) gene that cause familial non-haemolytic unconjugated hyperbilirubinaemias. Clin Chim Acta 1997;266(1):63–74.Google Scholar

Labrune, P, Myara, A, Hadchouel, M, Ronchi, F, Bernard, O, Trivin, F, et al. Genetic heterogeneity of Crigler-Najjar syndrome type I: a study of 14 cases. Hum Genet 1994;94(6):693–7.Google Scholar

Sinaasappel, M, Jansen, PL. The differential diagnosis of Crigler-Najjar disease, types 1 and 2, by bile pigment analysis. Gastroenterology 1991;100(3):783–9.Google Scholar

Rubaltelli, FF. Current drug treatment options in neonatal hyperbilirubinaemia and the prevention of kernicterus. Drugs 1998;56(1):23–30.Google Scholar

van der Veere, CN, Sinaasappel, M, McDonagh, AF, Rosenthal, P, Labrune, P, Odievre, M, et al. Current therapy for Crigler-Najjar syndrome type 1: report of a world registry. Hepatology 1996;24(2):311–15.Google Scholar

Rubaltelli, FF, Novello, A, Zancan, L, Vilei, MT, Muraca, M. Serum and bile bilirubin pigments in the differential diagnosis of Crigler-Najjar disease. Pediatrics 1994;94(4 Pt 1):553–6.Google Scholar

van de Steeg, E, Stranecky, V, Hartmannova, H, Noskova, L, Hrebicek, M, Wagenaar, E, et al. Complete OATP1B1 and OATP1B3 deficiency causes human Rotor syndrome by interrupting conjugated bilirubin reuptake into the liver. J Clin Invest 2012;122(2):519–28.Google Scholar

Wolkoff, AW, Wolpert, E, Pascasio, FN, Arias, IM. Rotor’s syndrome. A distinct inheritable pathophysiologic entity. Am J Med 1976;60(2):173–9.Google Scholar

Shimizu, Y, Naruto, H, Ida, S, Kohakura, M. Urinary coproporphyrin isomers in Rotor’s syndrome: a study in eight families. Hepatology 1981;1(2):173–8.Google Scholar

Jirsa, M, Knisely, AS, Schinkel, A, Kmoch, S. (1993). Rotor syndrome. In: Adam, MP, Ardinger, HH, Pagon, RA, Wallace, SE, Bean, LJH, Stephens, K, et al., (Eds.). GeneReviews®. Available at: www.ncbi.nlm.nih.gov/books/NBK114805/Google Scholar

Dubin, IN, Johnson, FB. Chronic idiopathic jaundice with unidentified pigment in liver cells: a new clinicopathologic entity with a report of 12 cases. Medicine 1954;33(3):155–97.Google Scholar

Toh, S, Wada, M, Uchiumi, T, Inokuchi, A, Makino, Y, Horie, Y, et al. Genomic structure of the canalicular multispecific organic anion-transporter gene (MRP2/cMOAT) and mutations in the ATP-binding-cassette region in Dubin-Johnson syndrome. Am J Hum Genet 1999;64(3):739–46.Google Scholar

Frank, M, Doss, M, de Carvalho, DG. Diagnostic and pathogenetic implications of urinary coproporphyrin excretion in the Dubin-Johnson syndrome. Hepatogastroenterology 1990;37(1):147–51.Google Scholar

Chen, HL, Li, HY, Wu, JF, Wu, SH, Chen, HL, Yang, YH, et al. Panel-based next-generation sequencing for the diagnosis of cholestatic genetic liver diseases: clinical utility and challenges. J Pediatr 2019;205:153–9 e6.Google Scholar

Machida, I, Wakusawa, S, Sanae, F, Hayashi, H, Kusakabe, A, Ninomiya, H, et al. Mutational analysis of the MRP2 gene and long-term follow-up of Dubin-Johnson syndrome in Japan. J Gastroenterol 2005;40(4):366–70.Google Scholar

References

Balistreri, WF, Bezerra, JA, Jansen, P, Karpen, SJ, Shneider, BL, Suchy, FJ. Intrahepatic cholestasis: summary of an American Association for the Study of Liver Diseases single-topic conference. Hepatology 2005;42:222–35.Google Scholar

Feldman, AG, Sokol, RJ. Neonatal cholestasis: emerging molecular diagnostics and potential novel therapeutics. Nat Rev Gastroenterol Hepatol 2019;16(6):346–60.Google Scholar

Bull, LN, Thompson, RJ. Progressive familial intrahepatic cholestasis. Clin Liver Dis 2018;22:657–69.Google Scholar

Baker, A, Kerkar, N, Todorova, L, Kamath, BM, Houwen, RHJ. Systematic review of progressive familial intrahepatic cholestasis. Clin Res Hepatol Gastroenterol 2018;3(1):20–36.Google Scholar

Droge, C, Bonus, M, Baumann, U, Klindt, C, Lainka, E, Kathemann, S, Brinkert, F, et al. Sequencing of FIC1, BSEP and MDR3 in a large cohort of patients with cholestasis revealed a high number of different genetic variants. J Hepatol 2017;67:1253–64.Google Scholar

Vitale, G, Gitto, S, Raimondi, F, Mattiaccio, A, Mantovani, V, Vukotic, R, D’Errico, A, et al. Cryptogenic cholestasis in young and adults: ATP8B1, ABCB11, ABCB4, and TJP2 gene variants analysis by high-throughput sequencing. J Gastroenterol 2018;53:945–58.Google Scholar

Strautnieks, SS, Bull, LN, Knisely, AS, Kocoshis, SA, Dahl, N, Arnell, H, Sokal, E, et al. A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis. Nat Genet 1998;20:233–8.Google Scholar

Davit-Spraul, A, Fabre, M, Branchereau, S, Baussan, C, Gonzales, E, Stieger, B, Bernard, O, et al. ATP8B1 and ABCB11 analysis in 62 children with normal gamma-glutamyl transferase progressive familial intrahepatic cholestasis (PFIC): phenotypic differences between PFIC1 and PFIC2 and natural history. Hepatology 2010;51:1645–55.Google Scholar

Davit-Spraul, A, Gonzales, E, Baussan, C, Jacquemin, E. Progressive familial intrahepatic cholestasis. Orphanet J Rare Dis 2009;4:1.Google Scholar

Paulusma, CC, Elferink, RP, Jansen, PL. Progressive familial intrahepatic cholestasis type 1. Semin Liver Dis 2010;30:117–24.Google Scholar

Pawlikowska, L, Strautnieks, S, Jankowska, I, Czubkowski, P, Emerick, K, Antoniou, A, Wanty, C, et al. Differences in presentation and progression between severe FIC1 and BSEP deficiencies. J Hepatol 2010;53:170–8.Google Scholar

Lykavieris, P, van Mil, S, Cresteil, D, Fabre, M, Hadchouel, M, Klomp, L, Bernard, O, et al. Progressive familial intrahepatic cholestasis type 1 and extrahepatic features: no catch-up of stature growth, exacerbation of diarrhea, and appearance of liver steatosis after liver transplantation. J Hepatol 2003;39:447–52.Google Scholar

Miyagawa-Hayashino, A, Egawa, H, Yorifuji, T, Hasegawa, M, Haga, H, Tsuruyama, T, Wen, MC, et al. Allograft steatohepatitis in progressive familial intrahepatic cholestasis type 1 after living donor liver transplantation. Liver Transpl 2009;15:610–18.Google Scholar

Knisely, AS. Progressive familial intrahepatic cholestasis: an update. Pediatr Dev Pathol 2004;7:309–14.Google Scholar

Morotti, RA, Suchy, FJ, Magid, MS. Progressive familial intrahepatic cholestasis (PFIC) type 1, 2, and 3: a review of the liver pathology findings. Semin Liver Dis 2011;31:3–10.Google Scholar

Bull, LN, Carlton, VE, Stricker, NL, Baharloo, S, DeYoung, JA, Freimer, NB, Magid, MS, et al. Genetic and morphological findings in progressive familial intrahepatic cholestasis (Byler disease [PFIC-1] and Byler syndrome): evidence for heterogeneity. Hepatology 1997;26:155–64.Google Scholar

Klomp, LW, Vargas, JC, van Mil, SW, Pawlikowska, L, Strautnieks, SS, van Eijk, MJ, Juijn, JA, et al. Characterization of mutations in ATP8B1 associated with hereditary cholestasis. Hepatology 2004;40:27–38.Google Scholar

Frankenberg, T, Miloh, T, Chen, FY, Ananthanarayanan, M, Sun, AQ, Balasubramaniyan, N, Arias, I, et al. The membrane protein ATPase class I type 8B member 1 signals through protein kinase C zeta to activate the farnesoid X receptor. Hepatology 2008;48:1896–1905.Google Scholar

van der Velden, LM, Stapelbroek, JM, Krieger, E, van den Berghe, PV, Berger, R, Verhulst, PM, Holthuis, JC, et al. Folding defects in P-type ATP 8B1 associated with hereditary cholestasis are ameliorated by 4-phenylbutyrate. Hepatology 2010;51:286–96.Google Scholar

Pawlikowska, L, Groen, A, Eppens, EF, Kunne, C, Ottenhoff, R, Looije, N, Knisely, AS, et al. A mouse genetic model for familial cholestasis caused by ATP8B1 mutations reveals perturbed bile salt homeostasis but no impairment in bile secretion. Hum Mol Genet 2004;13:881–92.Google Scholar

Groen, A, Kunne, C, Oude Elferink, RP. Increased serum concentrations of secondary bile salts during cholate feeding are due to coprophagy. A study with wild-type and Atp8b1-deficient mice. Mol Pharm 2006;3:756–61.Google Scholar

Stapelbroek, JM, Peters, TA, van Beurden, DH, Curfs, JH, Joosten, A, Beynon, AJ, van Leeuwen, BM, et al. ATP8B1 is essential for maintaining normal hearing. Proc Natl Acad Sci U S A 2009;106:9709–14.Google Scholar

Ray, NB, Durairaj, L, Chen, BB, McVerry, BJ, Ryan, AJ, Donahoe, M, Waltenbaugh, AK, et al. Dynamic regulation of cardiolipin by the lipid pump Atp8b1 determines the severity of lung injury in experimental pneumonia. Nat Med 2010;16:1120–7.Google Scholar

Takatsu, H, Tanaka, G, Segawa, K, Suzuki, J, Nagata, S, Nakayama, K, Shin, HW. Phospholipid flippase activities and substrate specificities of human type IV P-type ATPases localized to the plasma membrane. J Biol Chem 2014;289:33543–56.Google Scholar

Paulusma, CC, Folmer, DE, Ho-Mok, KS, de Waart, DR, Hilarius, PM, Verhoeven, AJ, Oude Elferink, RP. ATP8B1 requires an accessory protein for endoplasmic reticulum exit and plasma membrane lipid flippase activity. Hepatology 2008;47:268–78.Google Scholar

Liu, L, Zhang, L, Zhang, L, Yang, F, Zhu, X, Lu, Z, Yang, Y, et al. Hepatic Tmem30a deficiency causes intrahepatic cholestasis by impairing expression and localization of bile salt transporters. Am J Pathol 2017;187:2775–87.Google Scholar

Verhulst, PM, van der Velden, LM, Oorschot, V, van Faassen, EE, Klumperman, J, Houwen, RH, Pomorski, TG, et al. A flippase-independent function of ATP8B1, the protein affected in familial intrahepatic cholestasis type 1, is required for apical protein expression and microvillus formation in polarized epithelial cells. Hepatology 2010;51:2049–60.Google Scholar

Paulusma, CC, de Waart, DR, Kunne, C, Mok, KS, Elferink, RP. Activity of the bile salt export pump (ABCB11) is critically dependent on canalicular membrane cholesterol content. J Biol Chem 2009;284:9947–54.Google Scholar

Groen, A, Romero, MR, Kunne, C, Hoosdally, SJ, Dixon, PH, Wooding, C, Williamson, C, et al. Complementary functions of the flippase ATP8B1 and the floppase ABCB4 in maintaining canalicular membrane integrity. Gastroenterology 2011;141:1927–37 e1921–4.Google Scholar

Ujhazy, P, Ortiz, D, Misra, S, Li, S, Moseley, J, Jones, H, Arias, IM. Familial intrahepatic cholestasis 1: studies of localization and function. Hepatology 2001;34:768–75.Google Scholar

Chen, F, Ananthanarayanan, M, Emre, S, Neimark, E, Bull, LN, Knisely, AS, Strautnieks, SS, et al. Progressive familial intrahepatic cholestasis, type 1, is associated with decreased farnesoid X receptor activity. Gastroenterology 2004;126:756–64.Google Scholar

Chen, F, Ellis, E, Strom, SC, Shneider, BL. ATPase Class I Type 8B Member 1 and protein kinase C zeta induce the expression of the canalicular bile salt export pump in human hepatocytes. Pediatr Res 2010;67:183–7.Google Scholar

Strautnieks, SS, Kagalwalla, AF, Tanner, MS, Knisely, AS, Bull, L, Freimer, N, Kocoshis, SA, et al. Identification of a locus for progressive familial intrahepatic cholestasis PFIC2 on chromosome 2q24. Am J Hum Genet 1997;61:630–3.Google Scholar

Strautnieks, SS, Byrne, JA, Pawlikowska, L, Cebecauerova, D, Rayner, A, Dutton, L, Meier, Y, et al. Severe bile salt export pump deficiency: 82 different ABCB11 mutations in 109 families. Gastroenterology 2008;134:1203–14.Google Scholar

Ananthanarayanan, M, Balasubramanian, N, Makishima, M, Mangelsdorf, DJ, Suchy, FJ. Human bile salt export pump promoter is transactivated by the farnesoid X receptor/bile acid receptor. J Biol Chem 2001;276:28857–65.Google Scholar

Alissa, FT, Jaffe, R, Shneider, BL. Update on progressive familial intrahepatic cholestasis. J Pediatr Gastroenterol Nutr 2008;46:241–52.Google Scholar

Jansen, PL, Strautnieks, SS, Jacquemin, E, Hadchouel, M, Sokal, EM, Hooiveld, GJ, Koning, JH, et al. Hepatocanalicular bile salt export pump deficiency in patients with progressive familial intrahepatic cholestasis. Gastroenterology 1999;117:1370–9.Google Scholar

Evason, K, Bove, KE, Finegold, MJ, Knisely, AS, Rhee, S, Rosenthal, P, Miethke, AG, et al. Morphologic findings in progressive familial intrahepatic cholestasis 2 (PFIC2): correlation with genetic and immunohistochemical studies. Am J Surg Pathol 2011;35:687–96.Google Scholar

Thompson, R, Strautnieks, S. BSEP: function and role in progressive familial intrahepatic cholestasis. Semin Liver Dis 2001;21:545–50.Google Scholar

Knisely, AS. Progressive familial intrahepatic cholestasis: a personal perspective. Pediatr Dev Pathol 2000;3:113–25.Google Scholar

Byrne, JA, Strautnieks, SS, Ihrke, G, Pagani, F, Knisely, AS, Linton, KJ, Mieli-Vergani, G, et al. Missense mutations and single nucleotide polymorphisms in ABCB11 impair bile salt export pump processing and function or disrupt pre-messenger RNA splicing. Hepatology 2009;49:553–67.Google Scholar

Wang, R, Salem, M, Yousef, IM, Tuchweber, B, Lam, P, Childs, SJ, Helgason, CD, et al. Targeted inactivation of sister of P-glycoprotein gene (spgp) in mice results in nonprogressive but persistent intrahepatic cholestasis. Proc Natl Acad Sci U S A 2001;98:2011–16.Google Scholar

Hayashi, H, Takada, T, Suzuki, H, Akita, H, Sugiyama, Y. Two common PFIC2 mutations are associated with the impaired membrane trafficking of BSEP/ABCB11. Hepatology 2005;41:916–24.Google Scholar

Imagawa, K, Takayama, K, Isoyama, S, Tanikawa, K, Shinkai, M, Harada, K, Tachibana, M, et al. Generation of a bile salt export pump deficiency model using patient-specific induced pluripotent stem cell-derived hepatocyte-like cells. Sci Rep 2017;7:41806.Google Scholar

Whitington, PF, Whitington, GL. Partial external diversion of bile for the treatment of intractable pruritus associated with intrahepatic cholestasis. Gastroenterology 1988;95:130–6.Google Scholar

Wang, KS, Tiao, G, Bass, LM, Hertel, PM, Mogul, D, Kerkar, N, Clifton, M, et al. Analysis of surgical interruption of the enterohepatic circulation as a treatment for pediatric cholestasis. Hepatology 2017;65:1645–54.Google Scholar

Naoi, S, Hayashi, H, Inoue, T, Tanikawa, K, Igarashi, K, Nagasaka, H, Kage, M, et al. Improved liver function and relieved pruritus after 4-phenylbutyrate therapy in a patient with progressive familial intrahepatic cholestasis type 2. J Pediatr 2014;164:1219–27 e1213.Google Scholar

Gonzales, E, Grosse, B, Schuller, B, Davit-Spraul, A, Conti, F, Guettier, C, Cassio, D, et al. Targeted pharmacotherapy in progressive familial intrahepatic cholestasis type 2: evidence for improvement of cholestasis with 4-phenylbutyrate. Hepatology 2015;62:558–66.Google Scholar

Hasegawa, Y, Hayashi, H, Naoi, S, Kondou, H, Bessho, K, Igarashi, K, Hanada, K, et al. Intractable itch relieved by 4-phenylbutyrate therapy in patients with progressive familial intrahepatic cholestasis type 1. Orphanet J Rare Dis 2014;9:89.Google Scholar

Mehl, A, Bohorquez, H, Serrano, MS, Galliano, G, Reichman, TW. Liver transplantation and the management of progressive familial intrahepatic cholestasis in children. World J Transplant 2016;6:278–90.Google Scholar

Mali, VP, Fukuda, A, Shigeta, T, Uchida, H, Hirata, Y, Rahayatri, TH, Kanazawa, H, et al. Total internal biliary diversion during liver transplantation for type 1 progressive familial intrahepatic cholestasis: a novel approach. Pediatr Transplant 2016;20:981–6.Google Scholar

Jara, P, Hierro, L, Martinez-Fernandez, P, Alvarez-Doforno, R, Yanez, F, Diaz, MC, Camarena, C, et al. Recurrence of bile salt export pump deficiency after liver transplantation. N Engl J Med 2009;361:1359–67.Google Scholar

Sundaram, SS, Sokol, RJ. The multiple facets of ABCB4 (MDR3) deficiency. Curr Treat Options Gastroenterol 2007;10:495–503.Google Scholar

Reichert, MC, Lammert, F. ABCB4 gene aberrations in human liver disease: an evolving spectrum. Semin Liver Dis 2018;38:299–307.Google Scholar

Schatz, SB, Jungst, C, Keitel-Anselmo, V, Kubitz, R, Becker, C, Gerner, P, Pfister, ED, et al. Phenotypic spectrum and diagnostic pitfalls of ABCB4 deficiency depending on age of onset. Hepatol Commun 2018;2:504–14.Google Scholar

Jacquemin, E, De Vree, JM, Cresteil, D, Sokal, EM, Sturm, E, Dumont, M, Scheffer, GL, et al. The wide spectrum of multidrug resistance 3 deficiency: from neonatal cholestasis to cirrhosis of adulthood. Gastroenterology 2001;120:1448–58.Google Scholar

Lucena, JF, Herrero, JI, Quiroga, J, Sangro, B, Garcia-Foncillas, J, Zabalegui, N, Sola, J, et al. A multidrug resistance 3 gene mutation causing cholelithiasis, cholestasis of pregnancy, and adulthood biliary cirrhosis. Gastroenterology 2003;124:1037–42.Google Scholar

Jacquemin, E, Cresteil, D, Manouvrier, S, Boute, O, Hadchouel, M. Heterozygous non-sense mutation of the MDR3 gene in familial intrahepatic cholestasis of pregnancy. Lancet 1999;353:210–11.Google Scholar

Delaunay, JL, Durand-Schneider, AM, Dossier, C, Falguieres, T, Gautherot, J, Davit-Spraul, A, Ait-Slimane, T, et al. A functional classification of ABCB4 variations causing progressive familial intrahepatic cholestasis type 3. Hepatology 2016;63:1620–31.Google Scholar

Jacquemin, E, Hadchouel, M. Genetic basis of progressive familial intrahepatic cholestasis. J Hepatol 1999;31:377–81.Google Scholar

Delaunay, JL, Durand-Schneider, AM, Delautier, D, Rada, A, Gautherot, J, Jacquemin, E, Ait-Slimane, T, et al. A missense mutation in ABCB4 gene involved in progressive familial intrahepatic cholestasis type 3 leads to a folding defect that can be rescued by low temperature. Hepatology 2009;49:1218–27.Google Scholar

Smit, JJ, Schinkel, AH, Oude Elferink, RP, Groen, AK, Wagenaar, E, van Deemter, L, Mol, CA, et al. Homozygous disruption of the murine mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease. Cell 1993;75:451–62.Google Scholar

Fickert, P, Fuchsbichler, A, Wagner, M, Zollner, G, Kaser, A, Tilg, H, Krause, R, et al. Regurgitation of bile acids from leaky bile ducts causes sclerosing cholangitis in Mdr2 (Abcb4) knockout mice. Gastroenterology 2004;127:261–74.Google Scholar

Aagenaes, O. Hereditary cholestasis with lymphoedema (Aagenaes syndrome, cholestasis-lymphoedema syndrome). New cases and follow-up from infancy to adult age. Scand J Gastroenterol 1998;33:335–45.Google Scholar

Shah, S, Conlin, LK, Gomez, L, Aagenaes, O, Eiklid, K, Knisely, AS, Mennuti, MT, et al. CCBE1 mutation in two siblings, one manifesting lymphedema-cholestasis syndrome, and the other, fetal hydrops. PLoS One 2013;8:e75770.Google Scholar

Drivdal, M, Trydal, T, Hagve, TA, Bergstad, I, Aagenaes, O. Prognosis, with evaluation of general biochemistry, of liver disease in lymphoedema cholestasis syndrome 1 (LCS1/Aagenaes syndrome). Scand J Gastroenterol 2006;41:465–71.Google Scholar

Drivdal, M, Holven, KB, Retterstol, K, Aagenaes, O, Kase, BF. A nine year follow-up study of patients with lymphoedema cholestasis syndrome 1 (LCS1/Aagenaes syndrome). Scand J Clin Lab Invest 2018;78:566–74.Google Scholar

Gissen, P, Tee, L, Johnson, CA, Genin, E, Caliebe, A, Chitayat, D, Clericuzio, C, et al. Clinical and molecular genetic features of ARC syndrome. Hum Genet 2006;120:396–409.Google Scholar

Gissen, P, Johnson, CA, Morgan, NV, Stapelbroek, JM, Forshew, T, Cooper, WN, McKiernan, PJ, et al. Mutations in VPS33B, encoding a regulator of SNARE-dependent membrane fusion, cause arthrogryposis-renal dysfunction-cholestasis (ARC)syndrome. Nat Genet 2004;36:400–4.Google Scholar

Sambrotta, M, Strautnieks, S, Papouli, E, Rushton, P, Clark, BE, Parry, DA, Logan, CV, et al. Mutations in TJP2 cause progressive cholestatic liver disease. Nat Genet 2014;46:326–8.Google Scholar

Girard, M, Lacaille, F, Verkarre, V, Mategot, R, Feldmann, G, Grodet, A, Sauvat, F, et al. MYO5B and bile salt export pump contribute to cholestatic liver disorder in microvillous inclusion disease. Hepatology 2014;60:301–10.Google Scholar

Qiu, YL, Gong, JY, Feng, JY, Wang, RX, Han, J, Liu, T, Lu, Y, et al. Defects in myosin VB are associated with a spectrum of previously undiagnosed low gamma-glutamyltransferase cholestasis. Hepatology 2017;65:1655–69.Google Scholar

Esteve, C, Francescatto, L, Tan, PL, Bourchany, A, De Leusse, C, Marinier, E, Blanchard, A, et al. Loss-of-function mutations in UNC45A cause a syndrome associating cholestasis, diarrhea, impaired hearing, and bone fragility. Am J Hum Genet 2018;102:364–74.Google Scholar

Carlton, VE, Harris, BZ, Puffenberger, EG, Batta, AK, Knisely, AS, Robinson, DL, Strauss, KA, et al. Complex inheritance of familial hypercholanemia with associated mutations in TJP2 and BAAT. Nat Genet 2003;34:91–6.Google Scholar

Drouin, E, Russo, P, Tuchweber, B, Mitchell, G, Rasquin-Weber, A. North American Indian cirrhosis in children: a review of 30 cases. J Pediatr Gastroenterol Nutr 2000;31:395–404.Google Scholar

Freed, EF, Prieto, JL, McCann, KL, McStay, B, Baserga, SJ. NOL11, implicated in the pathogenesis of North American Indian childhood cirrhosis, is required for pre-rRNA transcription and processing. PLoS Genet 2012;8:e1002892.Google Scholar

Gomez-Ospina, N, Potter, CJ, Xiao, R, Manickam, K, Kim, MS, Kim, KH, Shneider, BL, et al. Mutations in the nuclear bile acid receptor FXR cause progressive familial intrahepatic cholestasis. Nat Commun 2016;7:10713.Google Scholar

References

Alagille, DHE, Thomassin, N. L’atresie des voies biliaires intrahepatiques avec voies biliaires extrahepatiques permeables chez l’enfant. J Par Pediatr 1969;301–18.Google Scholar

Emerick, KM, Rand, EB, Goldmuntz, E, Krantz, ID, Spinner, NB, Piccoli, DA. Features of Alagille syndrome in 92 patients: frequency and relation to prognosis. Hepatology 1999;29:822–9.Google Scholar

Kamath, BM, Spinner, NB, Emerick, KM, Chudley, AE, Booth, C, Piccoli, DA, Krantz, ID. Vascular anomalies in Alagille syndrome: a significant cause of morbidity and mortality. Circulation 2004;109:1354–8.Google Scholar

Crosnier, C, Lykavieris, P, Meunier-Rotival, M, Hadchouel, M. Alagille syndrome. The widening spectrum of arteriohepatic dysplasia. Clin Liver Dis 2000;4:765–78.Google Scholar

Kamath, BM, Bason, L, Piccoli, DA, Krantz, ID, Spinner, NB. Consequences of JAG1 mutations. J Med Genet 2003;40:891–5.Google Scholar

Li, L, Krantz, ID, Deng, Y, Genin, A, Banta, AB, Collins, CC, Qi, M, et al. Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1. Nat Genet 1997;16:243–51.Google Scholar

Oda, T, Elkahloun, AG, Pike, BL, Okajima, K, Krantz, ID, Genin, A, Piccoli, DA, et al. Mutations in the human Jagged1 gene are responsible for Alagille syndrome. Nat Genet 1997;16:235–42.Google Scholar

Warthen, DM, Moore, EC, Kamath, BM, Morrissette, JJ, Sanchez, P, Piccoli, DA, Krantz, ID, et al. Jagged1 (JAG1) mutations in Alagille syndrome: increasing the mutation detection rate. Hum Mutat 2006;27:436–43.Google Scholar

McDaniell, R, Warthen, DM, Sanchez-Lara, PA, Pai, A, Krantz, ID, Piccoli, DA, Spinner, NB. NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the notch signaling pathway. Am J Hum Genet 2006;79:169–73.Google Scholar

Alagille, D, Estrada, A, Hadchouel, M, Gautier, M, Odievre, M, Dommergues, JP. Syndromic paucity of interlobular bile ducts (Alagille syndrome or arteriohepatic dysplasia): review of 80 cases. J Pediatr 1987;110:195–200.Google Scholar

Deprettere, A, Portmann, B, Mowat, AP. Syndromic paucity of the intrahepatic bile ducts: diagnostic difficulty; severe morbidity throughout early childhood. J Pediatr Gastroenterol Nutr 1987;6:865–71.Google Scholar

Hoffenberg, EJ, Narkewicz, MR, Sondheimer, JM, Smith, DJ, Silverman, A, Sokol, RJ. Outcome of syndromic paucity of interlobular bile ducts (Alagille syndrome) with onset of cholestasis in infancy. J Pediatr 1995;127:220–4.Google Scholar

Quiros-Tejeira, RE, Ament, ME, Heyman, MB, Martin, MG, Rosenthal, P, Hall, TR, McDiarmid, SV, et al. Variable morbidity in Alagille syndrome: a review of 43 cases. J Pediatr Gastroenterol Nutr 1999;29:431–7.Google Scholar

Hofmann, JJ, Zovein, AC, Koh, H, Radtke, F, Weinmaster, G, Iruela-Arispe, ML. Jagged1 in the portal vein mesenchyme regulates intrahepatic bile duct development: insights into Alagille syndrome. Development 2010;137:4061–72.Google Scholar

Kamath, BM, Munoz, PS, Bab, N, Baker, A, Chen, Z, Spinner, NB, Piccoli, DA. A longitudinal study to identify laboratory predictors of liver disease outcome in Alagille syndrome. J Pediatr Gastroenterol Nutr;50:526–30.Google Scholar

Kamath, BM, Schwarz, KB, Hadzic, N. Alagille syndrome and liver transplantation. J Pediatr Gastroenterol Nutr 2010;50:11–15.Google Scholar

Bhadri, VA, Stormon, MO, Arbuckle, S, Lam, AH, Gaskin, KJ, Shun, A. Hepatocellular carcinoma in children with Alagille syndrome. J Pediatr Gastroenterol Nutr 2005;41:676–8.Google Scholar

Wetli, SC, Gralla, ES, Schibli, S, Stranzinger, E. Hepatocellular carcinoma and regenerating nodule in a 3-year-old child with Alagille syndrome. Pediatr Radiol 2010;40:1696–8.Google Scholar

Alhammad, A, Kamath, BM, Chami, R, Ng, VL, Chavhan, GB. Solitary hepatic nodule adjacent to the right portal vein: a common finding of Alagille syndrome? J Pediatr Gastroenterol Nutr 2016;62:226–32.Google Scholar

Rapp, JB, Bellah, RD, Maya, C, Pawel, BR, Anupindi, SA. Giant hepatic regenerative nodules in Alagille syndrome. Pediatr Radiol 2017;47:197–204.Google Scholar

Kahn, E. Paucity of interlobular bile ducts. Arteriohepatic dysplasia and nonsyndromic duct paucity. Perspect Pediatr Pathol 1991;14:168–215.Google Scholar

Alagille, D, Odievre, M, Gautier, M, Dommergues, JP. Hepatic ductular hypoplasia associated with characteristic facies, vertebral malformations, retarded physical, mental, and sexual development, and cardiac murmur. J Pediatr 1975;86:63–71.Google Scholar

Treem, WR, Krzymowski, GA, Cartun, RW, Pedersen, CA, Hyams, JS, Berman, M. Cytokeratin immunohistochemical examination of liver biopsies in infants with Alagille syndrome and biliary atresia. J Pediatr Gastroenterol Nutr 1992;15:73–80.Google Scholar

Dahms, BB, Petrelli, M, Wyllie, R, Henoch, MS, Halpin, TC, Morrison, S, Park, MC, et al. Arteriohepatic dysplasia in infancy and childhood: a longitudinal study of six patients. Hepatology 1982;2:350–8.Google Scholar

Watson, GH, Miller, V. Arteriohepatic dysplasia: familial pulmonary arterial stenosis with neonatal liver disease. Arch Dis Child 1973;48:459–66.Google Scholar

McElhinney, DB, Krantz, ID, Bason, L, Piccoli, DA, Emerick, KM, Spinner, NB, Goldmuntz, E. Analysis of cardiovascular phenotype and genotype-phenotype correlation in individuals with a JAG1 mutation and/or Alagille syndrome. Circulation 2002;106:2567–74.Google Scholar

Bauer, RC, Laney, AO, Smith, R, Gerfen, J, Morrissette, JJ, Woyciechowski, S, Garbarini, J, et al. Jagged1 (JAG1) mutations in patients with tetralogy of Fallot or pulmonic stenosis. Hum Mutat 2010;31:594–601.Google Scholar

Lykavieris, P, Crosnier, C, Trichet, C, Meunier-Rotival, M, Hadchouel, M. Bleeding tendency in children with Alagille syndrome. Pediatrics 2003;111:167–70.Google Scholar

Emerick, KM, Krantz, ID, Kamath, BM, Darling, C, Burrowes, DM, Spinner, NB, Whitington, PF, et al. Intracranial vascular abnormalities in patients with Alagille syndrome. J Pediatr Gastroenterol Nutr 2005;41:99–107.Google Scholar

Baird, LC, Smith, ER, Ichord, R, Piccoli, DA, Bernard, TJ, Spinner, NB, Scott, RM, et al. Moyamoya syndrome associated with Alagille syndrome: outcome after surgical revascularization. J Pediatr 2015;166:470–3.Google Scholar

Kohaut, J, Pommier, R, Guerin, F, Pariente, D, Jacquemin, E, Martelli, H, Branchereau, S. Abdominal arterial anomalies in children with Alagille syndrome: surgical aspects and outcomes of liver transplantation. J Pediatr Gastroenterol Nutr 2017;64:888–91.Google Scholar

Kamath, BM, Loomes, KM, Oakey, RJ, Krantz, ID. Supernumerary digital flexion creases: an additional clinical manifestation of Alagille syndrome. Am J Med Genet 2002;112:171–5.Google Scholar

Bales, CB, Kamath, BM, Munoz, PS, Nguyen, A, Piccoli, DA, Spinner, NB, Horn, D, et al. Pathologic lower extremity fractures in children with Alagille syndrome. J Pediatr Gastroenterol Nutr 2010;51:66–70.Google Scholar

Olsen, IE, Ittenbach, RF, Rovner, AJ, Leonard, MB, Mulberg, AE, Stallings, VA, Piccoli, DA, et al. Deficits in size-adjusted bone mass in children with Alagille syndrome. J Pediatr Gastroenterol Nutr 2005;40:76–82.Google Scholar

Kamath, BM, Loomes, KM, Oakey, RJ, Emerick, KE, Conversano, T, Spinner, NB, Piccoli, DA, et al. Facial features in Alagille syndrome: specific or cholestasis facies? Am J Med Genet 2002;112:163–70.Google Scholar

Kamath, BM, Bauer, RC, Loomes, KM, Chao, G, Gerfen, J, Hutchinson, A, Hardikar, W, et al. NOTCH2 mutations in Alagille syndrome. J Med Genet 2012;49:138–44.Google Scholar

Rennie, CA, Chowdhury, S, Khan, J, Rajan, F, Jordan, K, Lamb, RJ, Vivian, AJ. The prevalence and associated features of posterior embryotoxon in the general ophthalmic clinic. Eye 2005;19:396–9.Google Scholar

Hingorani, M, Nischal, KK, Davies, A, Bentley, C, Vivian, A, Baker, AJ, Mieli-Vergani, G, et al. Ocular abnormalities in Alagille syndrome. Ophthalmology 1999;106:330–7.Google Scholar

Nischal, KK, Hingorani, M, Bentley, CR, Vivian, AJ, Bird, AC, Baker, AJ, Mowat, AP, et al. Ocular ultrasound in Alagille syndrome: a new sign. Ophthalmology 1997;104:79–85.Google Scholar

Strachan, D, Kamath, B, Wengraf, C. How we do it: use of a venous cannulation needle for endoscopic Teflon injection to the vocal folds. J Laryngol Otol 1995;109:1184–5.Google Scholar

Kamath, BM, Spinner, NB, Rosenblum, ND. Renal involvement and the role of Notch signalling in Alagille syndrome. Nat Rev Nephrol 2013;9:409–18.Google Scholar

Kamath, BM, Podkameni, G, Hutchinson, AL, Leonard, LD, Gerfen, J, Krantz, ID, Piccoli, DA, et al. Renal anomalies in Alagille syndrome: a disease-defining feature. Am J Med Genet A 2012;158A:85–9.Google Scholar

Kamath, BM, Yin, W, Miller, H, Anand, R, Rand, EB, Alonso, E, Bucuvalas, J. Outcomes of liver transplantation for patients with Alagille syndrome: the studies of pediatric liver transplantation experience. Liver Transpl 2012;18:940–8.Google Scholar

Arvay, JL, Zemel, BS, Gallagher, PR, Rovner, AJ, Mulberg, AE, Stallings, VA, Haber, BA. Body composition of children aged 1 to 12 years with biliary atresia or Alagille syndrome. J Pediatr Gastroenterol Nutr 2005;40:146–50.Google Scholar

Rovner, AJ, Schall, JI, Jawad, AF, Piccoli, DA, Stallings, VA, Mulberg, AE, Zemel, BS. Rethinking growth failure in Alagille syndrome: the role of dietary intake and steatorrhea. J Pediatr Gastroenterol Nutr 2002;35:495–502.Google Scholar

Bucuvalas, JC, Horn, JA, Carlsson, L, Balistreri, WF, Chernausek, SD. Growth hormone insensitivity associated with elevated circulating growth hormone-binding protein in children with Alagille syndrome and short stature. J Clin Endocrinol Metab 1993;76:1477–82.Google Scholar

Kamath, BM, Piccoli, DA, Magee, JC, Sokol, RJ. Pancreatic insufficiency is not a prevalent problem in Alagille syndrome. J Pediatr Gastroenterol Nutr 2012;55:612–14.Google Scholar

Gliwicz, D, Jankowska, I, Wierzbicka, A, Miskiewicz-Chotnicka, A, Lisowska, A, Walkowiak, J. Exocrine pancreatic function in children with Alagille syndrome. Sci Rep 2016;6:35229.Google Scholar

Elisofon, SA, Emerick, KM, Sinacore, JM, Alonso, EM. Health status of patients with Alagille syndrome. J Pediatr Gastroenterol Nutr 2010;51(6):759–65.Google Scholar

Daniel, H, Leung, LGS, Wen, Y, Hawthorne, K, Binita, M, Kamath, VLN, et al. (ChiLDReN). Neurocognitive status in Alagille syndrome: results of a multi-center prospective observational study. Hepatology 2017;66:647–8.Google Scholar

Elisofon, SA, Emerick, KM, Sinacore, JM, Alonso, EM. Health status of patients with Alagille syndrome. J Pediatr Gastroenterol Nutr 2010;51:759–65.Google Scholar

Kamath, BM, Chen, Z, Romero, R, Fredericks, EM, Alonso, EM, Arnon, R, Heubi, J, et al. Quality of life and its determinants in a multicenter cohort of children with Alagille syndrome. J Pediatr 2015;167:390–6 e393.Google Scholar

Kamath, BM, Loomes, KM, Piccoli, DA. Medical management of Alagille syndrome. J Pediatr Gastroenterol Nutr 2010;50:580–6.Google Scholar

Kronsten, V, Fitzpatrick, E, Baker, A. Management of cholestatic pruritus in paediatric patients with Alagille syndrome: the King’s College Hospital experience. J Pediatr Gastroenterol Nutr 2013;57:149–54.Google Scholar

Narkewicz, M, Smith, D, Gregory, C, Lear, J, Osberg, I, Sokol, R. Effect of ursodeoxycholic acid therapy on hepatic function in children with intrahepatic cholestatic liver disease. J Pediatr Gastroenterol Nutr 1998;26:49–55.Google Scholar

Kamath, BM, Loomes, KM, Piccoli, DA. Medical management of Alagille syndrome. J Pediatr Gastroenterol Nutr 2010;50:580–6.Google Scholar

Mayo, MJ, Handem, I, Saldana, S, Jacobe, H, Getachew, Y, Rush, AJ. Sertraline as a first-line treatment for cholestatic pruritus. Hepatology 2007;45:666–74.Google Scholar

Thebaut, A, Habes, D, Gottrand, F, Rivet, C, Cohen, J, Debray, D, Jacquemin, E, et al. Sertraline as an additional treatment for cholestatic pruritus in children. J Pediatr Gastroenterol Nutr 2017;64:431–5.Google Scholar

Whitington, P, Whitington, G. Partial external diversion of bile for the treatment of intractable pruritus associated with intrahepatic cholestasis. Gastroenterology 1988;95:130–6.Google Scholar

Wang, KS, Tiao, G, Bass, LM, et al. Analysis of surgical interruption of the enterohepatic circulation as a treatment for pediatric cholestasis. Hepatology 2017;65:1645–54.Google Scholar

Kaye, AJ, Rand, EB, Munoz, PS, Spinner, NB, Flake, AW, Kamath, BM. Effect of Kasai procedure on hepatic outcome in Alagille syndrome. J Pediatr Gastroenterol Nutr 2010;51:319–21.Google Scholar

Fujishiro, J, Suzuki, K, Watanabe, M, Uotani, C, Takezoe, T, Takamoto, N, Hayashi, K. Outcomes of Alagille syndrome following the Kasai operation: a systematic review and meta-analysis. Pediatr Surg Int 2018;34:1073–7.Google Scholar

Wasserman, D, Zemel, BS, Mulberg, AE, John, HA, Emerick, KM, Barden, EM, Piccoli, DA, et al. Growth, nutritional status, body composition, and energy expenditure in prepubertal children with Alagille syndrome. J Pediatr 1999;134:172–7.Google Scholar

Razavi, RS, Baker, A, Qureshi, SA, Rosenthal, E, Marsh, MJ, Leech, SC, Rela, M, et al. Hemodynamic response to continuous infusion of dobutamine in Alagille’s syndrome. Transplantation 2001;72:823–8.Google Scholar

Kasahara, M, Kiuchi, T, Inomata, Y, Uryuhara, K, Sakamoto, S, Ito, T, Fujimoto, Y, et al. Living-related liver transplantation for Alagille syndrome. Transplantation 2003;75:2147–50.Google Scholar

Gurkan, A, Emre, S, Fishbein, TM, Brady, L, Millis, M, Birnbaum, A, Kim-Schluger, L, et al. Unsuspected bile duct paucity in donors for living-related liver transplantation: two case reports. Transplantation 1999;67:416–18.Google Scholar

Arnon, R, Annunziato, R, Miloh, T, Suchy, F, Sakworawich, A, Hiroshi, S, Kishore, I, et al. Orthotopic liver transplantation for children with Alagille syndrome. Pediatr Transplant 2010;14:622–8.Google Scholar

Gilbert, MA, Bauer, RC, Rajagopalan, R, Grochowski, CM, Chao, G, McEldrew, D, Nassur, JA, et al. Alagille syndrome mutation update: comprehensive overview of JAG1 and NOTCH2 mutation frequencies and insight into missense variant classification. Hum Mutat 2019;40:2197–220.Google Scholar

Byrne, JL, Harrod, MJ, Friedman, JM, Howard-Peebles, PN. del(20p) with manifestations of arteriohepatic dysplasia. Am J Med Genet 1986;24:673–8.Google Scholar

Spinner, NB, Colliton, RP, Crosnier, C, Krantz, ID, Hadchouel, M, Meunier-Rotival, M. Jagged1 mutations in Alagille syndrome. Hum Mutat 2001;17:18–33.Google Scholar

Stenson, PD, Mort, M, Ball, EV, Evans, K, Hayden, M, Heywood, S, Hussain, M, et al. The Human Gene Mutation Database: towards a comprehensive repository of inherited mutation data for medical research, genetic diagnosis and next-generation sequencing studies. Hum Genet 2017;136:665–77.Google Scholar

Warthen, DM, Moore, EC, Kamath, BM, Morrissette, JJ, Sanchez-Lara, PA, Piccoli, DA, Krantz, ID, et al. Jagged1 (JAG1) mutations in Alagille syndrome: increasing the mutation detection rate. Hum Mutat 2006;27:436–43.Google Scholar

Crosnier, C, Driancourt, C, Raynaud, N, Dhorne-Pollet, S, Pollet, N, Bernard, O, Hadchouel, M, et al. Mutations in JAGGED1 gene are predominantly sporadic in Alagille syndrome. Gastroenterology 1999;116:1141–8.Google Scholar

Kamath, BM, Thiel, BD, Gai, X, Conlin, LK, Munoz, PS, Glessner, J, Clark, D, et al. SNP array mapping of chromosome 20p deletions: genotypes, phenotypes, and copy number variation. Hum Mutat 2009;30:371–8.Google Scholar

Gridley, T. Notch signaling in vascular development and physiology. Development 2007;134:2709–18.Google Scholar

Crosnier, C, Attie-Bitach, T, Encha-Razavi, F, Audollent, S, Soudy, F, Hadchouel, M, Meunier-Rotival, M, et al. JAGGED1 gene expression during human embryogenesis elucidates the wide phenotypic spectrum of Alagille syndrome. Hepatology 2000;32:574–81.Google Scholar

McCright, B, Lozier, J, Gridley, T. A mouse model of Alagille syndrome: Notch2 as a genetic modifier of Jag1 haploinsufficiency. Development 2002;129:1075–82.Google Scholar

Andersson, ER, Chivukula, IV, Hankeova, S, Sjoqvist, M, Tsoi, YL, Ramskold, D, Masek, J, et al. Mouse model of Alagille syndrome and mechanisms of Jagged1 missense mutations. Gastroenterology 2018;154:1080–95.Google Scholar

Thakurdas, SM, Lopez, MF, Kakuda, S, Fernandez-Valdivia, R, Zarrin-Khameh, N, Haltiwanger, RS, Jafar-Nejad, H. Jagged 1 heterozygosity in mice results in a congenital cholangiopathy which is reversed by concomitant deletion of one copy of Poglut1 (Rumi). Hepatology 2016;63:550–65.Google Scholar

Eldadah, ZA, Hamosh, A, Biery, NJ, Montgomery, RA, Duke, M, Elkins, R, Dietz, HC. Familial Tetralogy of Fallot caused by mutation in the jagged1 gene. Hum Mol Genet 2001;10:163–9.Google Scholar

Ryan, MJ, Bales, C, Nelson, A, Gonzalez, DM, Underkoffler, L, Segalov, M, Wilson-Rawls, J, et al. Bile duct proliferation in Jag1/fringe heterozygous mice identifies candidate modifiers of the Alagille syndrome hepatic phenotype. Hepatology 2008;48:1989–97.Google Scholar

Tsai, EA, Gilbert, MA, Grochowski, CM, Underkoffler, LA, Meng, H, Zhang, X, Wang, MM, et al. THBS2 is a candidate modifier of liver disease severity in Alagille syndrome. Cell Mol Gastroenterol Hepatol 2016;2:663–75 e662.Google Scholar

Strazzabosco, M, Fabris, L. Development of the bile ducts: essentials for the clinical hepatologist. J Hepatol 2012;56:1159–70.Google Scholar

Fabris, L, Fiorotto, R, Spirli, C, Cadamuro, M, Mariotti, V, Perugorria, MJ, Banales, JM, et al. Pathobiology of inherited biliary diseases: a roadmap to understand acquired liver diseases. Nat Rev Gastroenterol Hepatol 2019;16:497–511.Google Scholar

Chen, HL, Li, HY, Wu, JF, Wu, SH, Chen, HL, Yang, YH, Hsu, YH, et al. Panel-based next-generation sequencing for the diagnosis of cholestatic genetic liver diseases: clinical utility and challenges. J Pediatr 2019;205:153–9 e156.Google Scholar

Shagrani, M, Burkholder, J, Broering, D, Abouelhoda, M, Faquih, T, El-Kalioby, M, Subhani, SN, et al. Genetic profiling of children with advanced cholestatic liver disease. Clin Genet 2017;92:52–61.89.Google Scholar

Kamath, BM et al. Outcomes of childhood cholestasis in Alagille syndrome: results of a multicenter observational study. Hepatol Commun 2020;4:387–98. Available at: https://aasldpubs.onlinelibrary.wiley.com/doi/10.1002/hep4.1468 [last accessed July 18, 2020].Google Scholar

References

Carter, BA, Shulman, R.J. Mechanisms of disease: update on the molecular etiology and fundamentals of parenteral nutrition associated cholestasis. Nat Clin Pract Gastroenterol Hepatol 2007;4(5);277–87.Google Scholar

Kelly, DA. Intestinal failure-associated liver disease: what do we know today? Gastroenterology 2006;130(2 Suppl 1):S70–7.Google Scholar

Javid, PJ, et al. The role of enteral nutrition in the reversal of parenteral nutrition-associated liver dysfunction in infants. J Pediatr Surg 2005;40(6):1015–18.Google Scholar

Christensen, RD, et al. Identifying patients, on the first day of life, at high-risk of developing parenteral nutrition-associated liver disease. J Perinatol 2007;27(5):284–90.Google Scholar

Javid, PJ, et al. A contemporary analysis of parenteral nutrition-associated liver disease in surgical infants. J Pediatr Surg;46(10):1913–17.Google Scholar

Mullick, FG, Moran, CA, Ishak, KG. Total parenteral nutrition: a histopathologic analysis of the liver changes in 20 children. Mod Pathol 1994;7(2):190–4.Google Scholar

Sondheimer, JM, Asturias, E, Cadnapaphornchai, M. Infection and cholestasis in neonates with intestinal resection and long-term parenteral nutrition. J Pediatr Gastroenterol Nutr 1998;27(2):131–7.Google Scholar

Yeop, I, et al. Hepatocellular carcinoma in a child with intestinal failure-associated liver disease. J Pediatr Gastroenterol Nutr 2012;54(5):695–7.Google Scholar

Quiros-Tejeira, RE, et al. Long-term parenteral nutritional support and intestinal adaptation in children with short bowel syndrome: a 25-year experience. J Pediatr 2004;145(2):157–63.Google Scholar

Luman, W, Shaffer, JL. Prevalence, outcome and associated factors of deranged liver function tests in patients on home parenteral nutrition. Clin Nutr 2002;21(4):337–43.Google Scholar

Roslyn, JJ, et al. Increased risk of gallstones in children receiving total parenteral nutrition. Pediatrics 1983;71(5):784–9.Google Scholar

Zambrano, E, et al. Total parenteral nutrition induced liver pathology: an autopsy series of 24 newborn cases. Pediatr Dev Pathol 2004;7(5):425–32.Google Scholar

Naini, BV, Lassman, CR. Total parenteral nutrition therapy and liver injury: a histopathologic study with clinical correlation. Hum Pathol 2012;43(6):826–33.Google Scholar

Fitzgibbons, SC, et al. Relationship between biopsy-proven parenteral nutrition-associated liver fibrosis and biochemical cholestasis in children with short bowel syndrome. J Pediatr Surg 2010;45(1):95–9; discussion 99.Google Scholar

Soden, JS, et al. Failure of resolution of portal fibrosis during omega-3 fatty acid lipid emulsion therapy in two patients with irreversible intestinal failure. J Pediatr 2010;156(2):327–31.Google Scholar

Van Gossum, A, et al. Transient elastography (FibroScan) is not correlated with liver fibrosis but with cholestasis in patients with long-term home parenteral nutrition. J Parenter Enteral Nutr 2015;39(6):719–24.Google Scholar

Hojsak, I, et al. ESPGHAN Committee on Nutrition Position Paper. Intravenous lipid emulsions and risk of hepatotoxicity in infants and children: a systematic review and meta-analysis. J Pediatr Gastroenterol Nutr 2016;62(5):776–92.Google Scholar

Beale, EF, et al. Intrahepatic cholestasis associated with parenteral nutrition in premature infants. Pediatrics 1979;64(3):342–7.Google Scholar

Rangel, SJ, et al. Parenteral nutrition-associated cholestasis: an American Pediatric Surgical Association Outcomes and Clinical Trials Committee systematic review. J Pediatr Surg 2012;47(1):225–40.Google Scholar

Balistreri, WF, Heubi, JE, Suchy, FJ. Immaturity of the enterohepatic circulation in early life: factors predisposing to “physiologic” maldigestion and cholestasis. J Pediatr Gastroenterol Nutr 1983;2(2):346–54.Google Scholar

Karpen, SJ. Nuclear receptor regulation of hepatic function. J Hepatol 2002;36(6):832–50.Google Scholar

Sokol, RJ, et al. Hepatic oxidant injury and glutathione depletion during total parenteral nutrition in weanling rats. Am J Physiol 1996;270(4 Pt 1):G691–700.Google Scholar

Squires, RH, et al. Natural history of pediatric intestinal failure: initial report from the Pediatric Intestinal Failure Consortium. J Pediatr 2012;161(4):723–8.Google Scholar

Hermans, D, et al. Early central catheter infections may contribute to hepatic fibrosis in children receiving long-term parenteral nutrition. J Pediatr Gastroenterol Nutr 2007;44(4):459–63.Google Scholar

El Kasmi, KC, et al. Toll like receptor 4-dependent Kupffer cell activation and liver injury in a novel mouse model of parenteral nutrition. Hepatology 2012;55(5):1518–28.Google Scholar

Duro, D, et al. Risk factors for parenteral nutrition-associated liver disease following surgical therapy for necrotizing enterocolitis: a Glaser Pediatric Research Network Study. J Pediatr Gastroenterol Nutr 2011;52(5):595–600.Google Scholar

Duro, D, Kamin, D, Duggan, C. Overview of pediatric short bowel syndrome. J Pediatr Gastroenterol Nutr 2008;47(Suppl 1):S33–6.Google Scholar

Steinbach, M, et al. Demographic and nutritional factors associated with prolonged cholestatic jaundice in the premature infant. J Perinatol 2008;28(2):129–35.Google Scholar

Forchielli, ML, et al. Aminosyn PF or trophamine: which provides more protection from cholestasis associated with total parenteral nutrition? J Pediatr Gastroenterol Nutr 1995;21(4):374–82.Google Scholar

Wright, K, et al. Increased incidence of parenteral nutrition-associated cholestasis with aminosyn PF compared to trophamine. J Perinatol 2003;23(6):444–50.Google Scholar

Guertin, F, et al. Effect of taurine on total parenteral nutrition-associated cholestasis. J Parenter Enteral Nutr 1991;15(3):247–51.Google Scholar

Tibboel, D, et al. Carnitine deficiency in surgical neonates receiving total parenteral nutrition. J Pediatr Surg 1990;25(4):418–21.Google Scholar

Wales, P.W., (2012). Intestinal failure-associated liver disease, in Duggan, CP and Jaksic, T, (Eds.), Clinical management of intestinal failure (pp. 247–63). K.M.G. Boca Raton, FL: CRC Press.Google Scholar

Buchman, AL, et al. Choline deficiency: a cause of hepatic steatosis during parenteral nutrition that can be reversed with intravenous choline supplementation. Hepatology 1995;22(5):1399–403.Google Scholar

Misra, S, et al. Plasma choline concentrations in children requiring long-term home parenteral nutrition: a case control study. J Parenter Enteral Nutr 1999;23(5):305–8.Google Scholar

Koletzko, B, et al. 1. Guidelines on Paediatric Parenteral Nutrition of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the European Society for Clinical Nutrition and Metabolism (ESPEN), Supported by the European Society of Paediatric Research (ESPR). J Pediatr Gastroenterol Nutr 2005;41 (Suppl 2):S1–87.Google Scholar

Le, HD, et al. Innovative parenteral and enteral nutrition therapy for intestinal failure. Semin Pediatr Surg 2010;19(1):27–34.Google Scholar

Colomb, V, et al. Role of lipid emulsions in cholestasis associated with long-term parenteral nutrition in children. J Parenter Enteral Nutr 2000;24(6):345–50.Google Scholar

Diamond, IR, et al. The role of parenteral lipids in the development of advanced intestinal failure-associated liver disease in infants: a multiple-variable analysis. J Parenter Enteral Nutr 2011;35(5):596–602.Google Scholar

Cober, MP, et al. Intravenous fat emulsions reduction for patients with parenteral nutrition-associated liver disease. J Pediatr 2012;160(3):421–7.Google Scholar

Diamond, IR, et al. Changing the paradigm: omegaven for the treatment of liver failure in pediatric short bowel syndrome. J Pediatr Gastroenterol Nutr 2009;48(2):209–15.Google Scholar

Puder, M, et al. Parenteral fish oil improves outcomes in patients with parenteral nutrition-associated liver injury. Ann Surg 2009;250(3):395–402.Google Scholar

Gura, KM, et al. Reversal of parenteral nutrition-associated liver disease in two infants with short bowel syndrome using parenteral fish oil: implications for future management. Pediatrics 2006;118(1):e197–201.Google Scholar

Lee, S, et al. Current clinical applications of omega-6 and omega-3 fatty acids. Nutr Clin Pract 2006;21(4):323–41.Google Scholar

Wanten, GJ, Calder, PC. Immune modulation by parenteral lipid emulsions. Am J Clin Nutr 2007;85(5):1171–84.Google Scholar

Schmocker, C, et al. Omega-3 fatty acids alleviate chemically induced acute hepatitis by suppression of cytokines. Hepatology 2007;45(4):864–9.Google Scholar

Diamond, IR, et al. The rationale for the use of parenteral omega-3 lipids in children with short bowel syndrome and liver disease. Pediatr Surg Int 2008;24(7):773–8.Google Scholar

Alwayn, IP, et al. Omega-3 fatty acid supplementation prevents hepatic steatosis in a murine model of nonalcoholic fatty liver disease. Pediatr Res 2005;57(3):445–52.Google Scholar

Clayton, PT, et al. Phytosterolemia in children with parenteral nutrition-associated cholestatic liver disease. Gastroenterology 1993;105(6):1806–13.Google Scholar

Iyer, KR, Spitz, L, Clayton, P. BAPS prize lecture: new insight into mechanisms of parenteral nutrition-associated cholestasis: role of plant sterols. British Association of Paediatric Surgeons. J Pediatr Surg 1998;33(1):1–6.Google Scholar

Van Aerde, JE, et al. Intravenous fish oil emulsion attenuates total parenteral nutrition-induced cholestasis in newborn piglets. Pediatr Res 1999;45(2):202–8.Google Scholar

Kurvinen, A, et al. Parenteral plant sterols and intestinal failure associated liver disease in neonates: a prospective nationwide study. J Pediatr Gastroenterol Nutr 2012;54(6):803–11.Google Scholar

Tazuke, Y, et al. Hepatic P-glycoprotein changes with total parenteral nutrition administration. J Parenter Enteral Nutr 2004;28(1):1–6.Google Scholar

Tazuke, Y, Teitelbaum, DH. Alteration of canalicular transporters in a mouse model of total parenteral nutrition. J Pediatr Gastroenterol Nutr 2009;48(2):193–202.Google Scholar

Carter, BA, et al. Stigmasterol, a soy lipid-derived phytosterol, is an antagonist of the bile acid nuclear receptor FXR. Pediatr Res 2007;62(3):301–6.Google Scholar

El Kasmi, K, et al. Soy lipid-derived phytosterols are responsible for parenteral nutrition associated liver injury (PNALI) in a mouse model. Hepatology 2011;54(4):89A.Google Scholar

El Kasmi, KC, et al. Macrophage-derived IL-1beta/NF-kappaB signaling mediates parenteral nutrition-associated cholestasis. Nat Commun 2018;9(1):1393.Google Scholar

Lee, WS, Sokol, RJ. Intestinal microbiota, lipids, and the pathogenesis of intestinal failure-associated liver disease. J Pediatr 2015;167(3):519–26.Google Scholar

Lavoie, JC, et al. Reduced bile flow associated with parenteral nutrition is independent of oxidant load and parenteral multivitamins. J Pediatr Gastroenterol Nutr 2005;41(1):108–14.Google Scholar

Blaszyk, H, et al. Hepatic copper in patients receiving long-term total parenteral nutrition. J Clin Gastroenterol 2005;39(4):318–20.Google Scholar

Fell, JM, et al. Manganese toxicity in children receiving long-term parenteral nutrition. Lancet 1996;347(9010):1218–21.Google Scholar

Frem, J, et al. Copper supplementation in parenteral nutrition of cholestatic infants. J Pediatr Gastroenterol Nutr 2010;50(6):650–4.Google Scholar

Oliveira, C, et al. Ethanol locks to prevent catheter-related bloodstream infections in parenteral nutrition: a meta-analysis. Pediatrics 2012;129(2):318–29.Google Scholar

Jensen, AR, et al. The association of cyclic parenteral nutrition and decreased incidence of cholestatic liver disease in patients with gastroschisis. J Pediatr Surg 2009;44(1):183–9.Google Scholar

Gura, KM, et al. Safety and efficacy of a fish-oil-based fat emulsion in the treatment of parenteral nutrition-associated liver disease. Pediatrics 2008;121(3):e678–86.Google Scholar

Cheung, HM, et al. Rescue treatment of infants with intestinal failure and parenteral nutrition-associated cholestasis (PNAC) using a parenteral fish-oil-based lipid. Clin Nutr 2009;28(2):209–12.Google Scholar

Goulet, O, et al. A new intravenous fat emulsion containing soybean oil, medium-chain triglycerides, olive oil, and fish oil: a single-center, double-blind randomized study on efficacy and safety in pediatric patients receiving home parenteral nutrition. J Parenter Enteral Nutr 2010;34(5):485–95.Google Scholar

Lapillonne, A, et al. ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition: lipids. Clin Nutr 2018;37(6 Pt B):2324–36.Google Scholar

Nandivada, P, et al. Lipid emulsions in the treatment and prevention of parenteral nutrition-associated liver disease in infants and children. Am J Clin Nutr 2016;103(2):629S–34S.Google Scholar

Nandivada, P, et al. Long-term fish oil lipid emulsion use in children with intestinal failure-associated liver disease. J Parenter Enteral Nutr 2017;41(6):930–7.Google Scholar

Gura, KM, Heme Biosynthesis and the Porphyrias in Children Calkins, KL, Puder, M. Use of fish oil intravenous lipid emulsions as monotherapy in the pediatric intestinal failure patient: beyond the package insert. Nutr Clin Pract 2020;35(1):108–18.Google Scholar

Ong, ML, et al. Two-year neurodevelopment and growth outcomes for preterm neonates who received low-dose intravenous soybean oil. J Parenter Enteral Nutr 2018;42(2):352–60.Google Scholar

Diamond, IR, et al. Preventing the progression of intestinal failure-associated liver disease in infants using a composite lipid emulsion: a pilot randomized controlled trial of SMOFlipid. J Parenter Enteral Nutr 2017;41(5):866–77.Google Scholar

Belza, C, et al. An observational study of Smoflipid vs Intralipid on the evolution of intestinal failure-associated liver disease in infants with intestinal failure. J Parenter Enteral Nutr 2020;44(4):688–96.Google Scholar

Wang, C, et al. Long-term outcomes in children with intestinal failure-associated liver disease treated with 6 months of intravenous fish oil followed by resumption of intravenous soybean oil. J Parenter Enteral Nutr 2019;43(6):708–16.Google Scholar

Heubi, JE, et al. Tauroursodeoxycholic acid (TUDCA) in the prevention of total parenteral nutrition-associated liver disease. J Pediatr 2002;141(2):237–42.Google Scholar

Teitelbaum, DH, et al. Use of cholecystokinin-octapeptide for the prevention of parenteral nutrition-associated cholestasis. Pediatrics 2005;115(5):1332–40.Google Scholar

Abu-Elmagd, KM, et al. Five hundred intestinal and multivisceral transplantations at a single center: major advances with new challenges. Ann Surg 2009;250(4):567–81.Google Scholar

Websites for Further Information

Oley Foundation: https://oley.org/default.aspx

American Society for Parenteral and Enteral Nutrition: www.nutritioncare.org/

Short Bowel Syndrome Foundation: http://shortbowelfoundation.org/

GI Kids (NASPGHAN Foundation): https://gikids.org/digestive-topics/short-bowel-syndrome/

References

Langman, J. (1981). The digestive system. In: Langman’s medical embryology, 3rd ed. (pp. 217–20). Baltimore: Williams & Wilkins.Google Scholar

Subramaniam, P, Knisely, A, Portmann, B, et al. Diagnosis of Alagille syndrome – 25 years of experience at King’s College Hospital. J Pediatr Gastroenterol Nutr 2011;52(1):84–9.Google Scholar

Copeland-Halperin, LR, Kapoor, K, Piper, JB. Complicated triple gallbladder: clinical presentation and surgical approach. BMJ Case Rep 2016; 2016:bcr2016215901. doi: 10.1136/bcr-2016-215901Google Scholar

Park, JE, Choi, YH, Cheon, JE, et al. Gallbladder wall edema and ascites are independent predictors of progression to hepatic venoocclusive disease for children with hematopoietic stem cell transplantation. Eur Radiol 2018;28(6):2291–8.Google Scholar

Ternberg, JL, Keating, JP. Acute acalculous cholecystitis. Arch Surg 1975;110:543–7.Google Scholar

Wong, ML, Kaplan, S, Dunkle, LM, et al. Leptospirosis: a childhood disease. J Pediatr 1977;90:532–7.Google Scholar

Holcomb, GW Jr, O’Neill, JA, Holcomb, GW III. Cholecystitis cholelithiasis and common duct stones in children and adolescents. Ann Surg 1980;191:626–35.Google Scholar

Mateos-Corral, D, Garza-Luna, U, Gutierrez-Martin, A. Two reports of acute neonatal acalculous cholecystitis (necrotizing cholecystitis) in a two-week-old premature infant and a term infant. J Pediatr Surg 2006;41(3):e3–e5.Google Scholar

Sanders, R. The significance of sonographic gallbladder wall thickening. J Clin Ultrasound 1980;8:143–6.Google Scholar

Patriquin, HB, DiPietro, M, Barber, FE, et al. Sonography of thickened gallbladder wall: causes in children. AJR 1983;141:57–60.Google Scholar

Jeffrey, RB Jr, Sommer, FG. Follow-up sonography in suspected acalculous cholecystitis: preliminary clinical experience. J Ultrasound Med 1993;12:183–7.Google Scholar

Thampy, R, Khan, A, Zaki, IH, et al. Acute acalculous cholecystitis in hospitalized patients with hematologic malignancies and prognostic importance of gallbladder ultrasound findings. J Ultrasound Med 2019;38(1):51–61.Google Scholar

Swayne, LC. Acute acalculous cholecystitis: sensitivity in detection using technetium-99 m imiodiacetic acid cholescintigraphy. Radiology 1986;160:33–8.Google Scholar

Imamoglu, M, Sarihan, H, Sari, A, Ahmetoglu, A. Acute acalculous cholecystitis in children: diagnosis and treatment. J Pediatr Surg 2002;37:36–9.Google Scholar

Dumont, RC, Caniano, DA. Hypokinetic gallbladder disease: a cause of chronic abdominal pain in children and adolescents. J Pediatr Surg 1999;34:858–61.Google Scholar

Vegunta, RK, Raso, M, Pollock, J, Misra, S, Wallace, LJ, Torres, A Jr., Pearl, RH.. Biliary dyskinesia: the most common indication for cholecystectomy in children. Surgery 2005;138:726–31.Google Scholar

Snajdauf, J, Petru, O, Pycha, K, et al. Porcelain gallbladder with extrahepatic bile duct obstruction in a child. Pediatr Surg I 2006;22(3):293–6.Google Scholar

Kim, SC. Six-year-old girl with porcelain gallbladder. J Ultrasound Med 2019;38(1):51–61.Google Scholar

Beauregard, WG, Ferguson, WT. Milk of calcium cholecystitis. J Pediatr 1980;96:876–7.Google Scholar

Palasciano, G, Portincasa, P, Vinciguerra, V, et al. Gallstone prevalence and gallbladder volume in children and adolescents: an epidemiological ultrasonographic survey and relationship to body mass index. Am J Gastroenterol 1989;84:1378–82.Google Scholar

Barbara, L, Sama, C, Labate, AMM, et al. A population study on the prevalence of gallstone disease: the Sirmione Study. Hepatology 1987;7:913–17.Google Scholar

Nilsson, S. Gallbladder disease and sex hormones. Acta Chir Scand 1966;132:275–9.Google Scholar

Jorgensen, T. Prevalence of gallstones in a Danish population. Am J Epidemiol 1987;126:912–21.Google Scholar

Shaffer, EA, Small, DM. Gallstone disease: pathogenesis and management. Curr Probl Surg 1976;13:1–72.Google Scholar

Holcomb, GW Jr, O’Neill, JA, Holcomb, GW III. Cholecystitis cholelithiasis and common duct stones in children and adolescents. Ann Surg 1980;191:626–35.Google Scholar

Takiff, H, Funkalsrud, EW. Gallbladder disease in childhood. Am J Dis Child 1984;138: 565–8.Google Scholar

Friesen, CA, Roberts, CC. Cholelithiasis: clinical characteristics in children. Clin Pediatr 1989;7:294–8.Google Scholar

Stringer, MD, Soloway, RD, Taylor, DR, et al. Calcium carbonate gallstones in children. J Pediatr Surg 2007;42(10):1677–82.Google Scholar

Sears, HF, Golden, GT, Horsley, JS III. Cholecystitis in adolescents. Arch Surg 1973;106:651–3.Google Scholar

Holcomb, GW Jr, Holcomb, GW. Cholelithiasis in infants, children and adolescents. Pediatr Rev 1991;11:268–74.Google Scholar

Pokorny, WJ, Saleem, M, O’Gorman, RB, et al. Cholelithiasis and cholecystitis in childhood. Am J Surg 1984;148:742–4.Google Scholar

MacMillan, RW, Schullinger, JN, Santulli, RV. Cholelithiasis in childhood. Am J Surg 1974;127:689–92.Google Scholar

Harned, RK, Babbit, DP. Cholelithiasis in childhood. Radiology 1975;117:391–3.Google Scholar

Andrassy, RJ, Treadwell, TA, Ratner, IA. Gallbladder disease in childhood and adolescents. Am J Surg 1976;132:19–21.Google Scholar

Odom, FC, Oliver, BB, Kline, M. Gallbladder disease in patients 20 years of age and younger. South Med J 1976;69:1299–1300.Google Scholar

Grace, N, Rogers, B. Cholecystitis in childhood. Clin Pediatr 1977;16:179–81.Google Scholar

Reif, S, Sloven, DG, Lebenthal, E. Gallstones in children. Am J Dis Child 1991;145:105–8.Google Scholar

Goodman, DB. Cholelithiasis in persons under 25 years old. JAMA 1976;236:1731–2.Google Scholar

MacMillan, RW, Schullinger, JN, Santuli, TV. Cholelithiasis in childhood. Am J Surg 1974;127:689–92.Google Scholar

Bailey, PV, Connors, RH, Tracy, TF Jr, et al. Changing spectrum of cholelithiasis and cholecystitis in infants and children. Am J Surg 1989;158:585–8.Google Scholar

Strauss, RT. Cholelithiasis in childhood. Am J Dis Child 1969;117:689–92.Google Scholar

Bond, LR, Hatty, SR, Horn, MEC, et al. Gallstones in sickle cell disease in the United Kingdom. Br J Med 1987;295:234–6.Google Scholar

Schubert, TT. Hepatobiliary system in sickle cell disease. Gastroenterology 1986;90:2013–21.Google Scholar

Sarnaik, S, Slovis, TL, Corbett, DP, et al. Incidence of cholelithiasis in sickle-cell anemia using the ultrasonic gray-scale technique. J Pediatrics 1980;96:1005–8.Google Scholar

Matos, C, Avni, EF, Van Gansbeke, D, et al. Total parenteral nutrition (TPN) and gallbladder diseases in neonates. J Ultrasound Med 1987;6:243–8.Google Scholar

King, DR, Ginn-Pease, ME, Lloyd, TV, et al. Parenteral nutrition with associated cholelithiasis: another iatrogenic disease of infants and children. J Pediatr Surg 1987;22:593–6.Google Scholar

Roslyn, JJ, Berquist, WE, Pitt, HA, et al. Increased risk of gallstones in children receiving total parenteral nutrition. Pediatrics 1983;71:784–9.Google Scholar

Messing, B, Bories, C, Kunstlinger, F, et al.Does total parenteral nutrition induce gallbladder sludge formation and lithiasis? Gastroenterology 1983;84:1012–19.Google Scholar

Mashako, NNL, Cezard, J-P, Borge, N, et al. The effect of artificial feeding on cholestasis, gallbladder sludge and lithiasis in infants: correlation with plasma cholecystokinin levels. Clin Nutr 1991;10:320–7.Google Scholar

Odievre, M, Gautier, M, Hadchouel, M, et al. Severe familial intrahepatic cholestasis. Arch Dis Child 1973;48:806–12.Google Scholar

Schaad, UB, Suter, S, Gianella-Borradovi, A, et al. A comparison of ceftriaxone and cefuroxime for the treatment of bacterial meningitis in children. N Engl J Med 1990;522:141–7.Google Scholar

Mahmond, H, Schell, M, Pui, C-H. Cholelithiasis after treatment for childhood cancer. Cancer 1991;67:1439–42.Google Scholar

Percy, AK, Lane, JB. Rett syndrome: model of neurodevelopmental disorders. J Clin Neurol 2005;20:718–21.Google Scholar

Sakopoulos, AG, Gundry, S, Razzouk, AJ, Andrews, HG, Bailey, LL. Cholelithiasis in infant and pediatric heart transplant patients. Pediatr Transplant 2002;6:231–4.Google Scholar

Treem, WR, Malet, PF, Gourley, GR, Hyams, JS. Bile and stone analysis in two infants with brown pigment gallstones and infected bile. Gastroenterology 1989;96(2 Pt 1):519–23. doi: 10.1016/s0016-5085(89)91579-5Google Scholar

Admirand, WH, Small, DM. The physico-chemical basis of cholesterol gallstone formation in man. J Clin Invest 1968;47:1043–52.Google Scholar

Carey, MC, Small, DM. The physical chemistry of cholesterol solubility in bile: relationship to gallstone formation and dissolution in man. J Clin Invest 1978;61:998–1026.Google Scholar

Lee, SP, LaMont, JT, Carey, MC. Role of gallstone mucous hypersecretion in the evolution of cholesterol gallstone: studies in a prairie dog. J Clin Invest 1981;67:1712–23.Google Scholar

Cirillo, DJ, Wallace, RB, Rodabough, RJ, et al. Effect of estrogen therapy on gallbladder disease. JAMA 2005;293(3):330–9.Google Scholar

Bennion, LJ, Knowler, WC, Mott, DM, et al. Development of lithogenic bile during puberty in Pima Indians. N Engl J Med 1979;300:873–6.Google Scholar

von Bergmann, K, Becker, M, Leiss, O. Biliary cholesterol saturation in non-obese women and non-obese men before and after puberty. Eur J Clin Invest 1986;16:531–5.Google Scholar

Koebnick, C, Smith, N, Black, MH, et al. Pediatric obesity and gallstone disease. J Pediatr Gastroenterol Nutr. 2012. 55(3):328–33.Google Scholar

Fradin, K, Racine, AD, and Belamarich, PF. Obesity and symptomatic cholelithiasis in childhood: epidemiologic and case-control evidence for a strong relation. J Pediatr Gastroenterol Nutr. 2014. 58(1):102–6.Google Scholar

Angelico, M, Gandin, C, Canuzzi, P. Gallstones in cystic fibrosis: a critical reappraisal. Hepatology 1991;14:768–75.Google Scholar

Honore, LH. Cholesterol cholelithiasis in adolescent females. Arch Surg 1980;114:62–4.Google Scholar

Buimsohn, A, Albu, E, Geist, PH, et al. Cholelithiasis and teenage mothers. J Adolesc Health Care 1990;11:339–42.Google Scholar

Katiska, D, et al. Genetic and environmental influences on symptomatic gallstone disease: a Swedish study of 43,141 twin pairs. Hepatology 2005;41:1139–43.Google Scholar

He, J, et al. PXR prevents cholesterol gallstone disease by regulating biosynthesis and transport of bile salts. Gastroenterology 2011;140:2095–106.Google Scholar

Buch, S, et al. A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease. Nat Genet 2007;39:995–9.Google Scholar

Grunhage, F, et al. Increased gallstone risk in humans conferred by common variant of hepatic ATP-binding cassette transported for cholesterol. Hepatology 2007;46:793–801.Google Scholar

Kuo, KK, et al. Significant association of ABCG5 604Q and ABCG8 D19H polymorphisms with gallstone disease. Br J Surg 2008;95:1005–11.Google Scholar

Katsika, D, et al. Gallstone disease in Swedish twins: risk is associated with ABCG8 D19H genotype. J Intern Med 2010;267(3):279–85.Google Scholar

Joshi, AD, Andersson, C, Buch, S, et al. Four susceptibility loci for gallstone disease identified in a meta-analysis of genome-wide association studies. Gastroenterology 2016;151(2):351–63.Google Scholar

Ferkingstad, E, Oddsson, A, Gretarsdottir, S, et al. Genome-wide association meta-analysis yields 20 loci associated with gallstone disease. Nat Commun 2018;9(1):5101.Google Scholar

Renner, O, et al. A variant of the SLC10A2 gene encoding the apical sodium-dependent bile acid transporter is a risk factor for gallstone disease. PLoS One 2009;4:e7321.Google Scholar

Vasavda, N, et al. The linear effects of alpha-thalassemia, the UGT1A1 and HMOX1 polymorphisms on cholelithiasis in sickle cell disease. Br J Haematol 2007;138:263–70.Google Scholar

Wasmuth, HE, et al. Coinheritance of Gilbert syndrome-associated UGT1A1 mutation increases gallstone risk in cystic fibrosis. Hepatology 2006;43:738–41.Google Scholar

Gracie, WA, Ransohoff, DF. The natural history of silent gallstones. The innocent gallstone is not a myth. N Engl J Med 1982;307:798–800.Google Scholar

Comfort, MW, Gray, HK, Wilson, JM. The silent gallstone: a ten to twenty year follow-up of 112 cases. Ann Surg 1948;128:931–7.Google Scholar

Newman, KD, Marmon, LM, Attorri, R, et al. Laparoscopic cholecystectomy in pediatric patients. J Pediatr Surg 1991;26:1184–5.Google Scholar

Esposito, C, Gonzales Sabin, MA, Corcione, F, Sacco, R, Esposito, G, Settimi, A. Results and complications of laparoscopic cholecystectomy in childhood. Surg Endoosc 2001;15:890–2.Google Scholar

Sackmann, M, Ippisch, E, Sauerbruch, T, et al. Early gallstone recurrence rate after successful shock-wave therapy. Gastroenterology 1990;98:392–6.Google Scholar

Bogue, C, et al. Risk factors, complications, and outcomes of gallstones in children: a single-center review. J Pediatr Gastroenterol Nutr 2010;50(3):303–8.Google Scholar

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Section II - Cholestatic Liver Disease

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