Medical and nutritional management of cholestasis in infants and children

Liver Disease in Children, Third Edition

Volumn , Issue , 2007, Pages 190-231

  Feranchak, Andrew P ^a,b   Sokol, Ronald J ^c,d  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b CHILDREN S MEDICAL CENTER   (United States)

^c Nutrition Obesity Research Center at the University of Colorado   (United States)

^d CHILDREN S HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 43049091091     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1017/CBO9780511547409.012     Document Type: Chapter

References (522)

1. Kasai M. Treatment of biliary atresia with special reference to hepatic portoenterostomy and its modifications. Prog Pediatr Surg 1974;6:5.
2. Whitley RJ, Nahmias AJ, Soong SJ, et al. Vidarabine therapy of neonatal herpes simplex virus infection. Pediatrics 1980 Oct;66:495–501.
3. Ingall D, Musher D. Infectious diseases of the fetus and newborn infant. In: Remington JS, Klein JO, eds. Syphilis. Philadelphia: Saunders, 1983:335.
4. Wright DJ, Berry CL. Letter: liver involvement in congenital syphilis. Br J Vener Dis 1974;50:241.
5. Ray CG, Wedgwood RJ. Neonatal listeriosis. Six case reports and a review of the literature. Pediatrics 1964;34:378–92.
6. Seelinger H, Finger H. Infectious diseases of the fetus and newborn infant. In: Remington JS, Klein JO, eds. Listeriosis. Philadelphia: Saunders, 1983:264.
7. Huber GL. Tuberculosis. In: Remington J, Klein J, eds. Tuberculosis. Philadelphia: Saunders, 1983:570.
8. Couvreur J, Desmonts G. Congenital and maternal toxoplasmosis. A review of 300 congenital cases. Dev Med Child Neurol 1962;4:519–30.
9. Remington JS, Desmonts G. Infectious diseases of the fetus and newborninfant. In:Remington JS, Klein JO, eds. Toxoplasmosis. Philadelphia: Saunders, 1983:143.
10. Applebaum MN, Thaler MM. Reversibility of extensive liver damage in galactosemia. Gastroenterology 1975;69:496–502.
11. Komrower GM, Lee DH. Long-term follow-up of galactosaemia. Arch Dis Child 1970;45:367–73.
12. Hill A, Nordin PM, Zaleski WA. Dietary treatment of tyrosinosis. J Am Diet Assoc 1970;56:308–12.
13. Hostetter MK, Levy HL, Winter HS, et al. Evidence for liver disease preceding amino acid abnormalities in hereditary tyrosinemia. N Engl J Med 1983;308:1265–7.
14. Lindblad B, Lindstedt S, Steen G. On the enzymic defects in hereditary tyrosinemia. Proc Natl Acad Sci U S A 1977;74: 4641–5.
15. Starzl TE, Zitelli BJ, Shaw BWJr, et al. Changing concepts: liver replacement for hereditary tyrosinemia and hepatoma. J Pediatr 1985;106:604–6.
16. Weinberg AG, Mize CE, Worthen HG. The occurrence of hepatoma in the chronic form of hereditary tyrosinemia. J Pediatr 1976;88:434–8.
17. Lindstedt S, Holme E, Lock EA, et al. Treatment of hereditary tyrosinaemia type I by inhibition of 4-hydroxyphenylpyruvate dioxygenase. Lancet 1992;340:813–17.
18. Holme E, Lindstedt S, Lock E. Treatment of tyrosinemia type I with an enzyme inhibitor (NTBC). Int Pediatr 1995;10:41–3.
19. Mock DM, Perman JA, Thaler M, Morris RC Jr. Chronic fructose intoxication after infancy in children with hereditary fructose intolerance. A cause of growth retardation. N Engl J Med 1983;309:764–70.
20. Odievre M, Gentil C, Gautier M, Alagille D. Hereditary fructose intolerance in childhood. Diagnosis, management, and course in 55 patients. Am J Dis Child 1978;132:605–8.
21. Herman SP, Baggenstoss AH, Cloutier MD. Liver dysfunction and histologic abnormalities in neonatal hypopituitarism. J Pediatr 1975;87(6 pt 1):892–5.
22. Colombo C, Battezzati PM, Podda M, et al. Ursodeoxycholic acid for liver disease associated with cystic fibrosis: a doubleblind multicenter trial. The Italian Group for the Study of Ursodeoxycholic Acid in Cystic Fibrosis. Hepatology 1996;23: 1484–90.
23. Sokol RJ, Durie PR. Recommendations for management of liver and biliary tract disease in cystic fibrosis. Cystic Fibrosis Foundation Hepatobiliary Disease Consensus Group. J Pediatr Gastroenterol Nutr 1999;28(suppl 1):S1–13.
24. Balistreri WF. Inborn errors of bile acid metabolism: clinical and therapeutic aspects. In:Hofmann A, Paumgartner G, Stiehl A, eds. Bile acids in gastroenterology: basic and clinical advances (proceedings of the 13th International Bile Acid Symposium). London: Kluwer Academic Publishers, 1995:333–53.
25. Daugherty CC, Setchell KD, Heubi JE, Balistreri WF. Resolution of liver biopsy alterations in three siblings with bile acid treatment of an inborn error of bile acid metabolism (delta 4–3-oxosteroid 5 beta-reductase deficiency). Hepatology 1993;18:1096–101.
26. Jacquemin E, Hermans D, Myara A, et al. Ursodeoxycholic acid therapy in pediatric patients with progressive familial intrahepatic cholestasis. Hepatology 1997;25:519–23.
27. Setchell K, O’Connell N. Inborn errors of bile acid biosynthesis: update on biochemical aspects. In: Hofmann A, Paumgartner G, Stiehl A, eds. Bile acids in gastroenterology: basic and clinical advances. London: Kluwer Academic Publishers, 1995:129–36.
28. Shamieh I, Kibort P, Suchy F, Freese D. Antioxidant therapy for neonatal iron storage disease. Pediatr Res 1993;33:109A. 29.
29. Zimmerman H. Hepatotoxicity. New York: Appleton-Century- Crofts, 1978.
30. Levy HL, Sepe SJ, Shih VE, et al. Sepsis due to Escherichia coli in neonates with galactosemia. N Engl J Med 1977;297:823–5.
31. Ng SH, Rawstron JR. Urinary tract infections presenting with jaundice. Arch Dis Child 1971;46:173–6.
32. Cooke RJ, Whitington PF, Kelts D. Effect of taurine supplementation on hepatic function during short-term parenteral nutrition in the premature infant. J Pediatr Gastroenterol Nutr 1984;3:234–8.
33. Graham M, Tavill A, Halpin T, Louis L. The effect of amino acids on bile flow and sodium taurocholate excretion in the isolated perfused rat liver. Gastroenterology 1981;80:1334.
34. Vileisis RA, Inwood RJ, Hunt CE. Prospective controlled study of parenteral nutrition-associated cholestatic jaundice: effect of protein intake. J Pediatr 1980;96:893–7.
35. Duerksen DR, Van Aerde JE, Gramlich L, et al. Intravenous ursodeoxycholic acid reduces cholestasis in parenterally fed newborn piglets. Gastroenterology 1996;111:1111–17.
36. Spagnuolo MI, Iorio R, Vegnente A, Guarino A. Ursodeoxycholic acid for treatment of cholestasis in children on longterm total parenteral nutrition: a pilot study. Gastroenterology 1996;111:716–19.
37. Lilly JR, Altman RP, Schroter G, et al. Surgery of biliary atresia. Current status. Am J Dis Child 1975;129:1429–32.
38. Lilly JR, Karrer FM, Hall RJ, et al. The surgery of biliary atresia. Ann Surg 1989;210:289–94.
39. 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.
40. Barlow B, Tabor E, Blanc WA, et al. Choledochal cyst: a review of 19 cases. J Pediatr 1976;89:934–40.
41. Lilly JR, Weintraub WH, Altman RP. Spontaneous perforation of the extrahepatic bile ducts and bile peritonitis in infancy. Surgery 1974;75:664–73.
42. Lilly JR. Common bile duct calculi in infants and children. J Pediatr Surg 1980;15:577–80.
43. Rickham PP, Lee EY. Neonatal jaundice: surgical aspects. Clin Pediatr (Phila) 1964;71:197–208.
44. Scholmerich J, Becher MS, Schmidt K, et al. Influence of hydroxylation and conjugation of bile salts on their membranedamaging properties –studies on isolated hepatocytes and lipid membrane vesicles. Hepatology 1984;4:661–6.
45. Greim H, Trulzsch D, Roboz J, et al. Mechanism of cholestasis. 5. Bile acids in normal rat livers and in those after bile duct ligation. Gastroenterology 1972;63:837–45.
46. De Lange RJ, Glazer AN. Bile acids: antioxidants or enhancers of peroxidation depending on lipid concentration. Arch Biochem Biophys 1990;276:19–25.
47. Botla R, Spivey JR, Aguilar H, et al. Ursodeoxycholate (UDCA) inhibits the mitochondrial membrane permeability transition induced by glycochenodeoxycholate: a mechanism of UDCA cytoprotection. J Pharmacol Exp Ther 1995;272:930–8.
48. Sokol RJ, Devereaux M, Khandwala R, O’Brien K. Evidence for involvement of oxygen free radicals in bile acid toxicity to isolated rat hepatocytes. Hepatology 1993;17:869–81.
49. Faubion WA, Guicciardi ME, Miyoshi H, et al. Toxic bile salts induce rodent hepatocyte apoptosis via direct activation of Fas. J Clin Invest 1999;103:137–45.
50. Patel T, Gores GJ. Apoptosis and hepatobiliary disease. Hepatology 1995;21:1725–41.
51. Rodrigues CM, Fan G, Wong PY, et al. Ursodeoxycholic acid may inhibit deoxycholic acid-induced apoptosis by modulating mitochondrial transmembrane potential and reactive oxygen species production. Mol Med 1998;4:165–78.
52. Heuman DM, Pandak WM, Hylemon PB, Vlahcevic ZR. Conjugates of ursodeoxycholate protect against cytotoxicity of more hydrophobic bile salts: in vitro studies in rat hepatocytes and human erythrocytes. Hepatology 1991;14:920–6.
53. Galle PR, Theilmann L, Raedsch R, et al. Ursodeoxycholate reduces hepatotoxicity of bile salts in primary human hepatocytes. Hepatology 1990;12(3 pt 1):486–91.
54. Hillaire S, Ballet F, Franco D, et al. Effects of ursodeoxycholic acid and chenodeoxycholic acid on human hepatocytes in primary culture. Hepatology 1995;22:82–7.
55. Lillienau J, Crombie DL, Munoz J, et al. Negative feedback regulation of the ileal bile acid transport system in rodents. Gastroenterology 1993;104:38–46.
56. Hofmann AF. Pharmacology of ursodeoxycholic acid, an enterohepatic drug. Scand J Gastroenterol Suppl 1994;204:1–15.
57. Kitani K, Ohta M, Kanai S. Tauroursodeoxycholate prevents biliary protein excretion induced by other bile salts in the rat. Am J Physiol 1985;248(4 pt 1):G40#1–27.
58. Shimokura GH, Mc Gill JM, Schlenker T, Fitz JG. Ursodeoxycholate increases cytosolic calcium concentration and activates Cl- currents in a biliary cell line. Gastroenterology 1995; 109:965–72.
59. Berthelot P, Erlinger S, Dhumeaux D, Preaux AM. Mechanism of phenobarbital-induced hypercholeresis in the rat. Am J Physiol 1970;219:809–13.
60. Miller NE, Nestel PJ. Altered bile acid metabolism during treatment with phenobarbitone. Clin Sci Mol Med Suppl 1973; 42:257–62.
61. Bloomer JR, Boyer JL. Phenobarbital effects in cholestatic liver diseases. Ann Intern Med 1975;82:310–17.
62. Makino I, Shinozaki K, Yoshino K, Nakagawa S. [Dissolution of cholesterol gallstones by long-term administration of ursodeoxycholic acid]. Nippon Shokakibyo Gakkai Zasshi 1975;72:690–702.
63. Bachrach WH, Hofmann AF. Ursodeoxycholic acid in the treatment of cholesterol cholelithiasis. Part I. Dig Dis Sci 1982;27: 737–61.
64. Ichida F. Clinical experiencewith ursodeoxycholic acid (S-urso) for chronic hepatitis. Diagn Treat 1961;36:388.
65. Hofmann AF, Popper H. Ursodeoxycholic acid for primary biliary cirrhosis. Lancet 1987;2:398–9.
66. Krahenbuhl S, Fischer S, Talos C, Reichen J. Ursodeoxycholate protectsoxidative mitochondrial metabolism frombile acid toxicity: dose-response study in isolated rat liver mitochondria. Hepatology 1994;20:1595–1601.
67. Heuman DM, Mills AS, McCall J, et al. Conjugates of ursodeoxycholate protect against cholestasis and hepatocellular necrosis caused by more hydrophobic bile salts. In vivo studies in the rat. Gastroenterology 1991;100:203–11.
68. Hofmann A. Targeting drugs to the enterohepatic circulation: lessons from bile acids and other endobiotics. J Controlled Release 1985;2:3–11.
69. Aldini R, Montagnani M, Roda A, et al. Intestinal absorption of bile acids in the rabbit: different transport rates in jejunum and ileum. Gastroenterology 1996;110:459–68.
70. Batta AK, Arora R, Salen G, et al. Characterization of serum and urinary bile acids in patients with primary biliary cirrhosis by gas-liquid chromatography-mass spectrometry: effect of ursodeoxycholic acid treatment. J Lipid Res 1989;30:1953–62.
71. Yoon YB, Hagey LR, Hofmann AF, et al. Effect of side-chain shortening on the physiologic properties of bile acids: hepatic transport and effect on biliary secretion of 23-nor-ursodeoxycholate in rodents. Gastroenterology 1986;90:837–52.
72. Elsing C, Sagesser H, Reichen J. Ursodeoxycholate-induced hypercholeresis in cirrhotic rats: further evidence for cholehepatic shunting. Hepatology 1994;20(4 pt 1):1048–54.
73. Knyrim K, Vakil N, Pfab R, Classen M. The effects of intraduodenal bile acid administration on biliary secretion of ionized calcium and carbonate in man. Hepatology 1989;10:134–42.
74. Lazaridis KN, Tietz P, Wu T, et al. Alternative splicing of the rat sodium/bile acid transporter changes its cellular localization and transport properties. Proc Natl Acad Sci U S A 2000;97:11092–7.
75. Lazaridis KN, Pham L, Tietz P, et al. Rat cholangiocytes absorb bile acids at their apical domain via the ileal sodium-dependent bile acid transporter. J Clin Invest 1997;100:2714–21.
76. Erlinger S, Dumont M. Influence of UDCA on bile secretion. In: Paumgartner G, Stiehl A, Barbara L, Roda E, eds. Strategies for the treatment of hepatobiliary disease. Dordrecht: Kluwer Academic Publishers, 1990:35–42.
77. Spengler U, Pape GR, Hoffmann RM, et al. Differential expression of MHC class II subregion products on bile duct epithelial cells and hepatocytes in patients with primary biliary cirrhosis. Hepatology 1988;8:459–62.
78. Calmus Y, Gane P, Rouger P, Poupon R. Hepatic expression of class I and class II major histocompatibility complex molecules in primary biliary cirrhosis: effect of ursodeoxycholic acid. Hepatology 1990;11:12–15.
79. Calmus Y, Arvieux C, Gane P, et al. Cholestasis induces major histocompatibility complex class I expression in hepatocytes. Gastroenterology 1992;102(4 pt 1):1371–7.
80. Innes GK, Nagafuchi Y, Fuller BJ, Hobbs KE. Increased expression of major histocompatibility antigens in the liver as a result of cholestasis. Transplantation 1988;45:749–52.
81. Calmus Y, Weill B, Ozier Y, et al. Immunosuppressive properties of chenodeoxycholic and ursodeoxycholic acids in the mouse. Gastroenterology 1992;103:617–21.
82. Kurktschiev D, Subat S, Adler D, Schentke KU. Immunomodulating effect of ursodeoxycholic acid therapy in patients with primary biliary cirrhosis. J Hepatol 1993;18:373–7.
83. Terasaki S, Nakanuma Y, Ogino H, et al. Hepatocellular and biliary expression of HLA antigens in primary biliary cirrhosis before and after ursodeoxycholic acid therapy. Am J Gastroenterol 1991;86:1194–9.
84. Poupon RE, Balkau B, Eschwege E, Poupon R. A multicenter, controlled trial of ursodiol for the treatment of primary biliary cirrhosis. UDCA-PBC Study Group. N Engl J Med 1991;324: 1548–54.
85. Heathcote EJ, Cauch-Dudek K, Walker V, et al. The Canadian Multicenter Double-blind Randomized Controlled Trial of ursodeoxycholic acid in primary biliary cirrhosis. Hepatology 1994;19:1149–56.
86. Lindor KD, Dickson ER, Baldus WP, et al. Ursodeoxycholic acid in the treatment of primary biliary cirrhosis. Gastroenterology 1994;106:1284–90.
87. Combes B, Carithers RL Jr, Maddrey WC, et al. A randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid in primary biliary cirrhosis. Hepatology 1995;22:759–66.
88. Lindor KD, Jorgensen RA, Therneau TM, et al. Ursodeoxycholic acid delays the onset of esophageal varices in primary biliary cirrhosis. Mayo Clin Proc 1997;72:1137–40.
89. Poupon RE, Lindor KD, Cauch-Dudek K, et al. Combined analysis of randomized controlled trials of ursodeoxycholic acid in primary biliary cirrhosis. Gastroenterology 1997;113:884–90.
90. Lindor K, Therneau T, Jorgensen R, et al. Effects of ursodeoxycholic acid on survival in patientswith primary biliary cirrhosis. Gastroenterology 1994;110:1515–18.
91. Pasha T, Heathcote J, Gabriel S, et al. Cost-effectiveness of ursodeoxycholic acid therapy in primary biliary cirrhosis. Hepatology 1999;29:21–6.
92. Beuers U, Spengler U, Kruis W, et al. Ursodeoxycholic acid for treatment of primary sclerosing cholangitis: a placebocontrolled trial. Hepatology 1992;16:707–14.
93. Lindor KD. Ursodiol for primary sclerosing cholangitis. Mayo Primary Sclerosing Cholangitis-Ursodeoxycholic Acid Study Group. N Engl J Med 1997;336:691–5.
94. Broome U, Glaumann H, Hultcrantz R, Forsum U. Distribution of HLA-DR, HLA-DP, HLA-DQ antigens in liver tissue from patients with primary sclerosing cholangitis. Scand J Gastroenterol 1990;25:54–8.
95. O’Brien CB, Senior JR, Rora-Mirchandani R, et al. Ursodeoxycholic acid for the treatment of primary sclerosing cholangitis: a 30-month pilot study. Hepatology 1991;14:838–47.
96. Chazouilleres O, Poupon R, Capron JP, et al. Ursodeoxycholic acid for primary sclerosing cholangitis. J Hepatol 1990;11:120–3.
97. Feigelson J, Anagnostopoulos C, Poquet M, et al. Liver cirrhosis in cystic fibrosis –therapeutic implications and long termfollow up. Arch Dis Child 1993;68:653–7.
98. Sinaasappel M. Hepatobiliary pathology in patients with cystic fibrosis. Acta Paediatr Scand Suppl 1989;363:45–50.
99. Cotting J, Lentze MJ, Reichen J. Effects of ursodeoxycholic acid treatment on nutrition and liver function in patients with cystic fibrosis and longstanding cholestasis. Gut 1990;31:918–21.
100. Colombo C, Setchell KD, Podda M, et al. Effect of UDCA on liver disease associated with cystic fibrosis. J Ped 1990;117:412–19.
101. Galabert C, Montet JC, Lengrand D, et al. Effects of ursodeoxycholic acid on liver function in patients with cystic fibrosis and chronic cholestasis. J Pediatr 1992;121:138–41.
102. van de Meeberg PC, Houwen RH, Sinaasappel M, et al. Lowdose versus high-dose ursodeoxycholic acid in cystic fibrosisrelated cholestatic liver disease. Results of a randomized study with 1-year follow-up. Scand J Gastroenterol 1997;32:369–73.
103. Colombo C, Castellani MR, Balistreri WF, et al. Scintigraphic documentation of an improvement in hepatobiliary excretory function after treatment with ursodeoxycholic acid in patients with cystic fibrosis and associated liver disease. Hepatology 1992;15:677–84.
104. Lindblad A, Glaumann H, Strandvik B. A two-year prospective study of the effect of ursodeoxycholic acid on urinary bile acid excretion and livermorphology in cystic fibrosis-associated liver disease. Hepatology 1998;27:166–74.
105. Lepage G, Paradis K, Lacaille F, et al. Ursodeoxycholic acid improves the hepatic metabolism of essential fatty acids and retinol in children with cystic fibrosis. J Pediatr 1997;130:52–8.
106. Thomas PS, Bellamy M, Geddes D. Malabsorption of vitamin E in cystic fibrosis improved after ursodeoxycholic acid. Lancet 1995;346:1230–1.
107. Bittner P, Posselt H, Sailor T, et al. The effect of treatment with ursodeoxycholic acid in cystic fibrosis and hepatopathy: results of a placebo-controlled study. In: Paumgartner G, Stiehl A, Gerok W, eds. Bile acids as therapeutic agents: from basic science to clinical practice. Lancaster: Kluwer Academic Publishers, 1991:345–8.
108. Balistreri WF, A-Kader H, Setchell K, and the Ursodeoxycholic Acid Study Group. Ursodeoxycholic acid therapy in pediatric patients with chronic cholestasis. In: Lentze M, Reichen J, eds. Paediatric cholestasis:novel approaches to treatment. Lancaster, England: Kluwer Academic Press, 1997:333–44.
109. Balistreri WF. Ursodeoxycholic acid in the treatment of pediatric liver disease. In: Fromm H, Leuschner U, eds. Proceedings of the Falk Symposium 84: Advances in basic and clinical bile acid research. London: Kluwer Acad Publishers, 1995;327–42.
110. Levy E, Bendayan M, Thibault L, et al. Lipoprotein abnormalities in two children with minimal biliary excretion. J Pediatr Gastroenterol Nutr 1995;20:432–9.
111. Krawinkel MB, Santer R, Oldigs HD. Ursodesoxycholic acid: effect on xanthomas in Alagille-Watson syndrome. J Pediatr Gastroenterol Nutr 1994;19:476–7.
112. Bijleveld CM, Vonk RJ, Kuipers F, et al. Benign recurrent intrahepatic cholestasis: altered bile acid metabolism. Gastroenterology 1989;97:427–32.
113. Crosignani A, Podda M, Bertolini E, et al. Failure of ursodeoxycholic acid to prevent a cholestatic episode in a patient with benign recurrent intrahepatic cholestasis: a study of bile acid metabolism. Hepatology 1991;13:1076–83.
114. Jacquemin E, Setchell KD, O’Connell NC, et al. A new cause of progressive intrahepatic cholestasis: 3 beta-hydroxy-C27- steroid dehydrogenase isomerase deficiency. J Pediatr 1994;125: 379–84.
115. A-Kader H, Santangelo J, Setchell K, et al. The effects of ursodeoxycholic acid (UDCA) therapy in biliary atresia (BA): a double blind randomized, placebo controlled trial. Ped Res 1993;33:97A. 116.
116. Nittono H, Tokita A, Hayashi M, et al. Ursodeoxycholic acid therapy in the treatment of biliary atresia. Biomed Pharmacother 1989;43:37–41.
117. A-Kader H, Heubi J, Setchell K, et al. The effects of UDCA therapy in children with EHBA. Gastroenterology 1990;98:A564.
118. Ullrich D, Rating D, Schroter W, et al. Treatment with ursodeoxycholic acid renders children with biliary atresia suitable for liver transplantation. Lancet 1987;2:1324.
119. Nittono H, Tokita A, Hayashi M, et al. Ursodeoxycholic acid in biliary atresia. Lancet 1988;1:528.
120. Schwarzenberg SJ, Bundy M. Ursodeoxycholic acid modifies gut-derived endotoxemia in neonatal rats. Pediatr Res 1994;35: 214–17.
121. Heubi JE, Wiechmann DA, Creutzinger V, et al. Tauroursodeoxycholic acid (TUDCA) in the prevention of total parenteral nutrition-associated liver disease. J Pediatr 2002;141: 237–42.
122. Boucher E, Jouanolle H, Andre P, et al. Interferon and ursodeoxycholic acid combined therapy in the treatment of chronic viral C hepatitis: results from a controlled randomized trial in 80 patients. Hepatology 1995;21:322–7.
123. Takano S, Ito Y, Yokosuka O, et al. A multicenter randomized controlled dose study of ursodeoxycholic acid for chronic hepatitis C. Hepatology 1994;20:558–64.
124. Angelico M, Gandin C, Pescarmona E, et al. Recombinant interferon-alpha and ursodeoxycholic acid versus interferonalpha alone in the treatment of chronic hepatitis C: a randomized clinical trial with long-termfollow-up. Am J Gastroenterol 1995;90:263–9.
125. Bellentani S, Podda M, Tiribelli C, et al. Ursodiol in the longtermtreatment of chronic hepatitis: a double-blindmulticenter clinical trial. J Hepatol 1993;19:459–64.
126. Lacaille F, Paradis K. The immunosuppressive effect of ursodeoxycholic acid: a comparative in vitro study on human peripheral blood mononuclear cells. Hepatology 1993;18:165–72.
127. Yoshikawa M, Tsujii T, Matsumura K, et al. Immunomodulatory effects of ursodeoxycholic acid on immune responses. Hepatology 1992;16:358–64.
128. Keiding S, Hockerstedt K, Bjoro K, et al. The Nordic multicenter double-blind randomized controlled trial of prophylactic ursodeoxycholic acid in liver transplant patients. Transplantation 1997;63:1591–4.
129. Pageaux GP, Blanc P, Perrigault PF, et al. Failure of ursodeoxycholic acid to prevent acute cellular rejection after liver transplantation. J Hepatol 1995;23:119–22.
130. Barnes D, Talenti D, Cammell G, et al. A randomized clinical trial of ursodeoxycholic acid as adjuvant treatment to prevent liver transplant rejection. Hepatology 1997;26:853–7.
131. Essell JH, Thompson JM, Harman GS, et al. Pilot trial of prophylactic ursodiol to decrease the incidence of veno-occlusive disease of the liver in allogeneic bone marrow transplant patients. Bone Marrow Transplant 1992;10:367–72.
132. Fried RH, Murakami CS, Fisher LD, et al. Ursodeoxycholic acid treatment of refractory chronic graft-versus-host disease of the liver. Ann Intern Med 1992;116:624–9.
133. Narkewicz MR, Smith D, Gregory C, et al. Effect of ursodeoxycholic acid therapy on hepatic function in children with intrahepatic cholestatic liver disease. J Pediatr Gastroenterol Nutr 1998;26:49–55.
134. Balistreri WF. Bile acid therapy in pediatric hepatobiliary disease: the role of ursodeoxycholic acid. J Pediatr Gastroenterol Nutr 1997;24:573–89.
135. Cowen AE, Korman MG, Hofmann AF, et al. Metabolism of lithocholate in healthy man. II. Enterohepatic circulation. Gastroenterology 1975;69:67–76.
136. Hirano S, Masuda N, Oda H. In vitro transformation of chenodeoxycholic acid and ursodeoxycholic acid by human intestinal flora, with particular reference to the mutual conversion between the two bile acids. J Lipid Res 1981;22:735–43.
137. Invernizzi P, Setchell KD, Crosignani A, et al. Differences in the metabolism and disposition of ursodeoxycholic acid and of its taurine-conjugated species in patients with primary biliary cirrhosis. Hepatology 1999;29:320–7.
138. Setchell KD, Rodrigues CM, Podda M, Crosignani A. Metabolism of orally administered tauroursodeoxycholic acid in patients with primary biliary cirrhosis. Gut 1996;38:439–46.
139. Kitani K, Kanai S. Tauroursodeoxycholateprevents taurocholate induced cholestasis. Life Sci 1982;30:515–23.
140. Miyake H, Tazuma S, Miura H, et al. Partial characterization of mechanisms of cytoprotective action of hydrophilic bile salts against hydrophobic bile salts in rats: relation to canalicular membrane fluidity and packing density. Dig Dis Sci 1999;44: 197–202.
141. Funaoka M, Komatsu M, Toyoshima I, et al. Tauroursodeoxycholic acid enhances phagocytosis of the cultured rat Kupffer cell. J Gastroenterol Hepatol 1999;14:652–8.
142. Beurs U, Nathanson M, Isales C, Boyer J. Tauroursodeoxycholic acid stimulates hepatocellular exocytosis and mobilizes extracellular Ca++ mechanisms defective in cholestasis. Clin Invest 1993;92:2984–93.
143. Kinbara S, Ishizaki K, Sakakura H, et al. Improvement of estradiol-17 beta-D-glucuronide-induced cholestasis by sodium tauroursodeoxycholate therapy in rats. Scand J Gastroenterol 1997;32:947–52.
144. Roda A, Piazza F, Baraldini M, et al. Taurohyodeoxycholic acid protects against taurochenodeoxycholic acid-induced cholestasis in the rat. Hepatology 1998;27:520–5.
145. Larghi A, Crosignani A, Battezzati PM, et al. Ursodeoxycholic and tauro-ursodeoxycholic acids for the treatment of primary biliary cirrhosis: a pilot crossover study. Aliment Pharmacol Ther 1997;11:409–14.
146. Crosignani A, Battezzati PM, Setchell KD, et al. Tauroursodeoxycholic acid for treatment of primary biliary cirrhosis. A dose-response study. Dig Dis Sci 1996;41:809–15.
147. Capron JP, Dumont M, Feldmann G, Erlinger S. Barbiturateinduced choleresis: possible independence from microsomal enzyme induction. Digestion 1977;15:556–65.
148. Simon FR, Sutherland E, Accatino L. Stimulation of hepatic sodium and potassium-activated adenosine triphosphatase activity by phenobarbital. Its possible role in regulation of bile flow. J Clin Invest 1977;59:849–61.
149. Sinatra FR. Cholestasis in infancy and childhood. Curr Probl Pediatr 1982;12:1–54.
150. Alagille D. Management of chronic cholestasis in childhood. Semin Liver Dis 1985;5:254–62.
151. Hahn TJ, Hendin BA, Scharp CR, Haddad JGJr. Effectof chronic anticonvulsant therapy on serum 25-hydroxycalciferol levels in adults. N Engl J Med 1972;287:900–4.
152. Ghent CN, Bloomer JR, Hsia YE. Efficacy and safety of longterm phenobarbital therapy of familial cholestasis. J Pediatr 1978;93:127–32.
153. Ferrari M, Barabas G, Matthews WS. Psychologicandbehavioral disturbance among epileptic children treated with barbiturate anticonvulsants. Am J Psychiatry 1983;140:112–13.
154. Brent DA, Crumrine PK, Varma RR, et al. Phenobarbital treatment and major depressive disorder in children with epilepsy. Pediatrics 1987;80:909–17.
155. Brent DA. Overrepresentation of epileptics in a consecutive series of suicide attempters seen at a children’s hospital, 1978–1983. J Am Acad Child Psychiatry 1986;25:242–6.
156. Brent DA, Crumrine PK, Varma R, et al. Phenobarbital treatment and major depressive disorder in children with epilepsy: a naturalistic follow-up. Pediatrics 1990;85:1086–91.
157. Karrer FM, Lilly JR. Corticosteroid therapy in biliary atresia. J Pediatr Surg 1985;20:693–5.
158. Meyers RL, Book LS, O’Gorman MA, et al. High-dose steroids, ursodeoxycholic acid, and chronic intravenous antibiotics improve bile flow after Kasai procedure in infants with biliary atresia. J Pediatr Surg 2003;38:406–11.
159. Rintala RJ, Lindahl H, Pohjavuori M. Total parenteral nutritionassociated cholestasis in surgical neonates may be reversed by intravenous cholecystokinin: a preliminary report. J Pediatr Surg 1995;30:827–30.
160. Teitelbaum DH, Han-Markey T, Schumacher RE. Treatment of parenteral nutrition-associated cholestasis with cholecystokinin-octapeptide. J Pediatr Surg 1995;30:1082–5.
161. Teitelbaum DH, Han-Markey T, Drongowski RA, et al. Use of cholecystokinin to prevent the development of parenteral nutrition-associated cholestasis. JPEN J Parenter Enteral Nutr 1997;21:100–3.
162. Teitelbaum DH, Tracy TF Jr, Aouthmany MM, et al. Use of cholecystokinin-octapeptide for the prevention of parenteral nutrition-associated cholestasis. Pediatrics 2005;115:1332–40.
163. Wagner M, Trauner M. Transcriptional regulation of hepatobiliary transport systems in health and disease: implications for a rationale approach to the treatment of intrahepatic cholestasis. Ann Hepatol 2005;4:77–99.
164. Liu Y, Binz J, Numerick MJ, et al. Hepatoprotection by the farnesoid X receptor agonist GW4064 in rat models of intraand extrahepatic cholestasis. J Clin Invest 2003;112:1678–87.
165. Fiorucci S, Clerici C, Antonelli E, et al. Protective effects of 6- ethyl chenodeoxycholic acid, a farnesoid X receptor ligand, in estrogen-induced cholestasis. J Pharmacol Exp Ther 2005;313: 604–12.
166. Saini SP, Sonoda J, Xu L, et al. A novel constitutive androstane receptor-mediated and CYP3A-independent pathway of bile acid detoxification. Mol Pharmacol 2004;65:292–300.
167. Huang W, Zhang J, Moore DD. A traditional herbal medicine enhances bilirubin clearance by activating the nuclear receptor CAR. J Clin Invest 2004;113:137–43.
168. Stedman CA, Liddle C, Coulter SA, et al. Nuclear receptors constitutive androstane receptor and pregnane X receptor ameliorate cholestatic liver injury. Proc Natl Acad Sci U S A 2005; 102:2063–8.
169. Zhang J, Huang W, Qatanani M, et al. The constitutive androstane receptor and pregnane X receptor function coordinately to prevent bile acid-induced hepatotoxicity. J Biol Chem 2004;279:49517–22.
170. Marschall HU, Wagner M, Zollner G, et al. Complementary stimulation of hepatobiliary transport and detoxification systems by rifampicin and ursodeoxycholic acid in humans. Gastroenterology 2005;129:476–85.
171. Friedman SL. Cytokines and fibrogenesis. Semin Liver Dis 1999;19:129–40.
172. Li D, Friedman SL. Liver fibrogenesis and the role of hepatic stellate cells: new insights and prospects for therapy. J Gastroenterol Hepatol 1999;14:618–33.
173. Siegelmann R, Peterkofsky B. Inhibition of collagen secretion from bone and culture fibroblasts by microtubular disruptive drugs. Proc Natl Acad Sci U S A 1972;69:892–6.
174. Scherft JP, Heersche JN. Accumulation of collagen-containing vacuoles in osteoblasts after administration of colchicine. Cell Tissue Res 1975;157:353–65.
175. Dinarello CA, Chusid MJ, Fauci AS, et al. Effect of prophylactic colchicine therapy on leukocyte function in patients with familial Mediterranean fever. Arthritis Rheum 1976;19:618–22.
176. Gordon S, Werb Z. Secretion of macrophage neutral proteinase is enhanced by colchicine. Proc Natl Acad Sci U S A 1976;73: 872–6.
177. Warnes TW, Smith A, Lee FI, et al. Acontrolled trial of colchicine in primary biliary cirrhosis. Trial design and preliminary report. J Hepatol 1987;5:1–7.
178. Kaplan MM, Alling DW, Zimmerman HJ, et al. A prospective trial of colchicine for primary biliary cirrhosis. N Engl J Med 1986;315:1448–54.
179. Kershenobich D, Vargas F, Garcia-Tsao G, et al. Colchicine in the treatment of cirrhosis of the liver. N Engl J Med 1988;318: 1709–13.
180. Klion FM, Fabry T, Zifroni A, Schaffner F. Progression of PBC with and without colchicine therapy. Hepatology 1990;12:420.
181. Zifroni A, Schaffner F. Long-term follow-up of patients with primary biliary cirrhosis on colchicine therapy. Hepatology 1991;14:990–3.
182. Collins J, Morecki R, Mc Phillips J, Gartner L. Colchicine treatment of paediatric chronic cholestatic liver disease. In: Lentze M, Reichen J, eds. Pediatric cholestasis: novel approaches to treatment. Dordrecht, The Netherlands: Kluwer Academic Publishers, 1992:305–8.
183. Morgan TR, Weiss DG, Nemchausky B, et al. Colchicine treatment of alcoholic cirrhosis: a randomized, placebo-controlled clinical trial of patient survival. Gastroenterology 2005;128: 882–90.
184. Hatziioannidou A, Cheesman P, Trivedi P, et al. Double blind controlled trial of colchicine versus placebo in extrahepatic biliary atresia: interim results. Hepatology 1992;16:60A. 185. Nimni ME, Bavetta LA. Collagen defect induced by penicillamine. Science 1965;150:905–7.
185. Deshmukh K, Nimni ME. A defect in the intramolecular and intermolecular cross-linking of collagen caused by penicillamine. II. Functional groups involved in the interaction process. J Biol Chem 1969;244:1787–95.
186. Walshe JM. Wilson’s disease; new oral therapy. Lancet 1956; 270:25–6.
187. Neuberger J, Christensen E, Portmann B, et al. Double blind controlled trial of d-penicillamine in patients with primary biliary cirrhosis. Gut 1985;26:114–19.
188. Bodenheimer HCJr, Schaffner F, Sternlieb I, et al. Aprospective clinical trial of D-penicillamine in the treatment of primary biliary cirrhosis. Hepatology 1985;5:1139–42.
189. Dickson ER, Fleming TR, Wiesner RH, et al. Trial of penicillamine in advanced primary biliary cirrhosis. N Engl J Med 1985;312:1011–15.
190. Oikarinen AI, Vuorio EI, Zaragoza EJ, et al. Modulation of collagen metabolism by glucocorticoids. Receptor-mediated effects of dexamethasone on collagen biosynthesis in chick embryo fibroblasts and chondrocytes. Biochem Pharmacol 1988;37: 1451–62.
191. Oikarinen AI, Uitto J, Oikarinen J. Glucocorticoid action on connective tissue: from molecular mechanisms to clinical practice. Med Biol 1986;64:221–30.
192. Weiner FR, Czaja MJ, Giambrone MA, et al. Transcriptional and posttranscriptional effects of dexamethasone on albumin and procollagen messenger RNAs in murine schistosomiasis. Biochemistry 1987;26:1557–62.
193. Jefferson DM, Reid LM, Giambrone MA, et al. Effects of dexamethasone on albumin and collagen gene expression in primary cultures of adult rat hepatocytes. Hepatology 1985;5:14–20.
194. Zhang M, Song G, Minuk GY. Effects of hepatic stimulator substance, herbal medicine, selenium/vitamin E, and ciprofloxacin on cirrhosis in the rat. Gastroenterology 1996;110:1150–5.
195. Chojkier M, Houglum K, Lee KS, Buck M. Long- and short-term D-alpha-tocopherol supplementation inhibits liver collagen alpha1(I) gene expression. Am J Physiol 1998; 275 (6 pt 1):G1480–5.
196. Houglum K, Brenner DA, Chojkier M. d-Alpha-tocopherol inhibits collagen alpha 1(I) gene expression in cultured human fibroblasts. Modulation of constitutive collagen gene expression by lipid peroxidation. J Clin Invest 1991;87:2230–5.
197. Houglum K, Venkataramani A, Lyche K, Chojkier M. A pilot study of the effects of d-alpha-tocopherol on hepatic stellate cell activation in chronic hepatitis C. Gastroenterology 1997;113:1069–73.
198. Stickel F, Brinkhaus B, Krahmer N, et al. Antifibrotic properties of botanicals in chronic liver disease. Hepatogastroenterology 2002;49:1102–8.
199. Rockey DC. Antifibrotic therapy in chronic liver disease. Clin Gastoenterol Hepatol 2005;3:95–107.
200. Gartung C, Matern S. Molecular regulation of sinusoidal liver bile acid transporters during cholestasis. Yale J Biol Med 1997; 70:355–63.
201. Koopen NR, Wolters H, Voshol P, et al. Decreased Na+- dependent taurocholate uptake and low expression of the sinusoidal Na+-taurocholate cotransporting protein (Ntcp) in livers of mdr2 P-glycoprotein-deficient mice. J Hepatol 1999;30: 14–21.
202. Gartung C, Ananthanarayanan M, Rahman MA, et al. Downregulation of expression and function of the rat liver Na+/bile acid cotransporter in extrahepatic cholestasis. Gastroenterology 1996;110:199–209.
203. Jones EA, Bergasa NV. The pruritus of cholestasis: from bile acids to opiate agonists. Hepatology 1990;11:884–7.
204. Maddrey WC, Van Thiel DH. Liver transplantation: an overview. Hepatology 1988;8:948–59.
205. Cauna N. Fine morphological changes in the penicillate nerve endings of human hairy skin during prolonged itching. Anat Rec 1977;188:1–11.
206. Herndon JH Jr. Pathophysiology of pruritus associatedwith elevatedbile acid levels in serum. Arch Intern Med 1972;130:632–7.
207. Schoenfield L. The relationship of bile acids to pruritus in hepatobiliary disease. In: Schiff L, Carey J, Dietschy J, eds. Bile salt metabolism. Springfield, IL: Charles C Thomas Publisher, 1969:257–65.
208. Garden JM, Ostrow JD, Roenigk HH Jr. Pruritus in hepatic cholestasis. Pathogenesis and therapy. Arch Dermatol 1985;121:1415–20.
209. Ghent CN, Bloomer JR, Klatskin G. Elevations in skin tissue levels of bile acids in human cholestasis: relation to serum levels and topruritus. Gastroenterology 1977;73:1125–30.
210. Freedman MR, Holzbach RT, Ferguson DR. Pruritus in cholestasis: no direct causative role for bile acid retention. Am J Med 1981;70:1011–16.
211. Silverberg DS, Iaina A, Reisin E, et al. Cholestyraminein uraemic pruritus. Br Med J 1977;1:752–3.
212. Chanarin I, Szur L. Letter: relief of intractable pruritis in polycythaemia rubra vera with cholestyramine. Br J Haematol 1975;29:669–70.
213. Thornton JR, Losowsky MS. Opioid peptides and primary biliary cirrhosis. BMJ 1988;297:1501–4.
214. Swain MG, Rothman RB, Xu H, et al. Endogenous opioids accumulate in plasma in a rat model of acute cholestasis. Gastroenterology 1992;103:630–5.
215. Reiz S, Westberg M. Side-effects of epidural morphine. Lancet 1980;2:203–4.
216. Ballantyne JC, Loach AB, Carr DB. Itching after epidural and spinal opiates. Pain 1988;33:149–60.
217. Bernstein JE, Grinzi RA. Butorphanol-induced pruritus antagonized by naloxone. J Am Acad Dermatol 1981;5:227–8.
218. Justins DM, Reynolds F. Intraspinal opiates and itching: a new reflex? Br Med J (Clin Res Ed) 1982;284:1401.
219. Graham-Smith D, Aronson J. Narcotic analgesics. In: Graham- Smith D, Aronson J, eds. Oxford textbook of clinical pharmacology and drug therapy. 2nd ed. New York: Oxford, 1992:641–4.
220. Jaffe J, Martin W. Opioid analgesics and antagonists. In: Gilman A, Goodman L, Rall T, Marad F, eds. The pharmacologic basis of therapeutics. 7th ed. New York: Mac Millan Publishing Co., 1985:491–531.
221. Bernstein JE, Swift R. Relief of intractable pruritus with naloxone. Arch Dermatol 1979;115:1366–7.
222. Bergasa NV, Thomas DA, Vergalla J, et al. Plasma from patientswith the pruritus of cholestasis induces opioid receptormediated scratching in monkeys. Life Sci 1993;53:1253–7.
223. Bergasa NV, Rothman RB, Vergalla J, et al. Central mu-opioid receptors are down-regulated in a rat model of cholestasis. J Hepatol 1992;15:220–4.
224. Gold MS, Redmond DE Jr, Kleber HD. Clonidine blocks acute opiate-withdrawal symptoms. Lancet 1978;2:599–602.
225. Charney DS, Heninger GR, Kleber HD. The combined use of clonidine and naltrexone as a rapid, safe, and effective treatment of abrupt withdrawal from methadone. Am J Psychiatry 1986;143:831–7.
226. Thornton JR, Losowsky MS. Plasma methionine enkephalin concentration and prognosis in primary biliary cirrhosis. BMJ 1988;297:1241–2.
227. Kastin AJ, Nissen C, Schally AV, Coy DH. Blood-brain barrier, half-time disappearance, and brain distribution for labeled enkephalin and a potent analog. Brain Res Bull 1976;1:583–9.
228. Rapoport SI, Klee WA, Pettigrew KD, Ohno K. Entry of opioid peptides into the central nervous system. Science 1980;207: 84–6.
229. Banks WA, Kastin AJ, Fischman AJ, et al. Carrier-mediated transport of enkephalins and N-Tyr-MIF-1 across blood-brain barrier. Am J Physiol 1986;251(4 pt 1):E477–82.
230. Summerfield JA. Naloxone modulates the perception of itch in man. Br J Clin Pharmacol 1980;10:180–3.
231. Sharp HL, Carey JB Jr, White JG, Krivit W. Cholestyramine therapy in patients with a paucity of intrahepatic bile ducts. J Pediatr 1967;71:723–36.
232. Palmer RH. Bile acids, liver injury, and liver disease. Arch Intern Med 1972;130:606–17.
233. Levy JS, Gelb AM, Stenger RJ, Javitt NB. Prolonged neonatal cholestasis: bile acid pattern and response to cholestyramine. Mt Sinai J Med 1979;46:169–73.
234. Ghent CN, Carruthers SG. Treatment of pruritus in primary biliary cirrhosis with rifampin. Results of a double-blind, crossover, randomized trial. Gastroenterology 1988;94:488–93.
235. Bachs L, Pares A, Elena M, et al. Comparison of rifampicin with phenobarbitone for treatment of pruritus in biliary cirrhosis. Lancet 1989;1:574–6.
236. Cynamon HA, Andres JM, Iafrate RP. Rifampin relieves pruritus in children with cholestatic liver disease. Gastroenterology 1990;98:1013–16.
237. Podesta A, Lopez P, Terg R, et al. Treatment of pruritus of primary biliary cirrhosis with rifampin. Dig Dis Sci 1991;36:216–20.
238. Bachs L, Pares A, Elena M, et al. Effects of long-termrifampicin administration in primary biliary cirrhosis. Gastroenterology 1992;102:2077–80.
239. Chretien Y, Poupon R, Gherardt M, et al. Bile acid glycine and taurine conjugates in serum of patients with PBC: effect of ursodeoxycholic acid treatment. Gut 1990;30:1110–15.
240. Stiehl A, Rudolph G, Raedsch R, et al. Ursodeoxycholic acidinduced changes of plasma and urinary bile acids in patients with primary biliary cirrhosis. Hepatology 1990;12(3 pt 1): 492–7.
241. Rail T, Schleifer L. Drugs effective in the therapy of epilepsies. In: Gilman A, Goodman L, Rail T, Murod F, eds. The pharmacologic basis of therapeutics. New York: Mac Millan, 1985: 457.
242. Hanid MA, Levi AJ. Phototherapy for pruritus in primarybiliary cirrhosis. Lancet 1980;2:530.
243. Perlstein SM. Phototherapy for primary biliary cirrhosis. Arch Dermatol 1981;117:608.
244. Person JR. Ultraviolet A (UV-A) and cholestatic pruritus. Arch Dermatol 1981;117:684.
245. Lauterburg BH, Pineda AA, Dickson ER, et al. Plasmaperfusion for the treatment of intractable pruritus of cholestasis. Mayo Clin Proc 1978;53:403–7.
246. Lauterburg BH, Pineda AA, Burgstaler E. Treatment of pruritus of cholestasis by plasma perfusion thru USP-charcoal coated glass beads. Lancet 1990;2:53–5.
247. Datta DV, Sherlock S. Treatment of pruritus of obstructive jaundice with cholestyramine. Br Med J 1963;5325:216–19.
248. Sweeney ME, Fletcher BJ, Rice CR, et al. Efficacy and compliance with cholestyramine bar versus powder in the treatment of hyperlipidemia. Am J Med 1991;90:469–73.
249. Yerushalmi B, Sokol RJ, Narkewicz MR, et al. Use of rifampin for severe pruritus in childrenwith chronic cholestasis. J Pediatr Gastroenterol Nutr 1999;29:442–7.
250. Gregorio GV, Ball CS, Mowat AP, Mieli-Vergani G. Effect of rifampicin in the treatment of pruritus in hepatic cholestasis. Arch Dis Child 1993;69:141–3.
251. Ohnhaus EE, Gerber-Taras E, Park BK. Enzyme-inducing drug combinations and their effects on liver microsomal enzyme activity in man. Eur J Clin Pharmacol 1983;24:247–50.
252. Galeazzi R, Lorenzini I, Orlandi F. Rifampicin-induced elevation of serum bile acids in man. Dig Dis Sci 1980;25:108–12.
253. Nakashima T, Sano A, Seto Y, et al. Unusual trihydroxy bile acids in the urine of patients treated with chenodeoxycholate, ursodeoxycholate or rifampicin and those with cirrhosis. Hepatology 1990;11:255–60.
254. Hollins PJ, Simmons AV. Jaundice associated with rifampicin. Tubercle 1970;51:328–32.
255. Scheuer PJ, Summerfield JA, Lal S, Sherlock S. Rifampicin hepatitis. A clinical and histological study. Lancet 1974;1:421–5.
256. Miguet JP, Mavier P, Soussy CJ, Dhumeaux D. Induction of hepatic microsomal enzymes after brief administration of rifampicin in man. Gastroenterology 1977;72(5 pt 1):924–6.
257. Brodie MJ, Boobis AR, Dollery CT, et al. Rifampicinandvitamin D metabolism. Clin Pharmacol Ther 1980;27:810–14.
258. Rothwell DL, Richmond DE. Hepatorenal failure with selfinitiated intermittent rifampicin therapy. Br Med J 1974;2: 481–2.
259. Bergasa NV, Alling DW, Talbot TL, et al. Effects of naloxone infusions in patients with the pruritus of cholestasis. A doubleblind, randomized, controlled trial. Ann Intern Med 1995;123: 161–7.
260. Terra SG, Tsunoda SM. Opioid antagonists in the treatment of pruritus from cholestatic liver disease. Ann Pharmacother 1998;32:1228–30.
261. Gal TJ, Di Fazio CA, Dixon R. Prolonged blockade of opioid effect with oral nalmefene. Clin Pharmacol Ther 1986;40:537–42.
262. Bergasa NV, Schmitt JM, Talbot TL, et al. Open-label trial of oral nalmefene therapy for the pruritus of cholestasis. Hepatology 1998;27:679–84.
263. Wolfhagen FH, Sternieri E, Hop WC, et al. Oral naltrexone treatment for cholestatic pruritus: a double-blind, placebocontrolled study. Gastroenterology 1997;113:1264–9.
264. Carson KL, Tran TT, Cotton P, et al. Pilot study of the use of naltrexone to treat the severe pruritus of cholestatic liver disease. Am J Gastroenterol 1996;91:1022–3.
265. Croop RS, Faulkner EB, Labriola DF. The safety profile of naltrexone in the treatment of alcoholism. Results from a multicenter usage study. The Naltrexone Usage Study Group. Arch Gen Psychiatry 1997;54:1130–5.
266. Sharp HL, Mirkin BL. Effect of phenobarbital on hyperbilirubinemia, bile acid metabolism, and microsomal enzyme activity in chronic intrahepatic cholestasis of childhood. J Pediatr 1972;81:116–26.
267. Balistreri WF, A-Kader H, Setchell K. UDCAtherapy in patients with Alagille syndrome (syndromic paucity of intrahepatic bile ducts): results of a multicenter pilot trial. Pediatr Res 1991;29:A99.
268. Balistreri WF, A-Kader H, Ryckman F, et al. Biochemical and clinical response to UDCA administration in pediatric patients with chronic cholestasis. In: Paumgartner G, Stiehl A, Gerok W, eds. Bile acids as therapeutic agents. Lancaster: Kluwer Academic Publishers, 1991:323–33.
269. Paradis K, Weber A. Sudden liver deterioration in infants receiving UDCA. Gastroenterology 1992;102:866.
270. Whitington PF, Whitington GL. Partial external diversion of bile for the treatment of intractable pruritus associated with intrahepatic cholestasis. Gastroenterology 1988;95:130–6.
271. Emond JC, Whitington PF. Selective surgical management of progressive familial intrahepatic cholestasis (Byler’s disease). J Pediatr Surg 1995;30:1635–41.
272. Gauderer MW, Boyle JT. Cholecystoappendicostomy in a child with Alagille syndrome. J Pediatr Surg 1997;32:166–7.
273. Rebhandl W, Felberbauer FX, Turnbull J, et al. Biliary diversion by use of the appendix (cholecystoappendicostomy) in progressive familial intrahepatic cholestasis. JPediatr Gastroenterol Nutr 1999;28:217–19.
274. Ng VL, Ryckman FC, Porta G, et al. Long-term outcome after partial external biliary diversion for intractable pruritus in patients with intrahepatic cholestasis. J Pediatr Gastroenterol Nutr 2000;30:152–6.
275. Kurbegov AC, Setchell KD, Haas JE, et al. Biliary diversion for progressive familial intrahepatic cholestasis: improved liver morphology and bile acid profile. Gastroenterology 2003; 125:1227–34.
276. Chen F, Ananthanarayanan M, Emre S, et al. Progressive familial intrahepatic cholestasis, type 1, is associated with decreased farnesoid X receptor activity. Gastroenterology 2004;126:756–64.
277. Whitington P, Freese D, Alonso E, et al. Surgery for treatment of Pediatric Cholestasis. In: Schoelmerich J, Sraub R, Lentntze MJ, Reichen J, eds. Pediatric cholestasis: novel approaches to treatment. London: Kluwer Academic Publishers, 1992:173.
278. Kalicinski PJ, Ismail H, Jankowska I, et al. Surgical treatment of progressive familial intrahepatic cholestasis: comparison of partial external biliary diversion and ileal bypass. Eur J Pediatr Surg 2003;13:307–11.
279. Stapelbroek JM, van Erpecum KJ, Klomp LW, et al. Nasobiliary drainage induces long-lasting remission in benign recurrent intrahepatic cholestasis. Hepatology 2006;43:51–53.
280. Duncan JS, Kennedy HJ, Triger DR. Treatment of pruritus due to chronic obstructive liver disease. Br Med J (Clin Res Ed) 1984; 289:22.
281. Alva J, Iber FL. Relief of the pruritus of jaundice with methandrostenolone and speculations on the nature of pruritus in liver disease. Am J Med Sci 1965;250:60–5.
282. Walt RP, Daneshmend TK, Fellows IW, Toghill PJ. Effect of stanozolol on itching in primary biliary cirrhosis. Br Med J (Clin Res Ed) 198827;296:607.
283. Osborn EC, Wootton ID, da Silva SL, Sherlock S. Serum-bileacid levels in liver disease. Lancet 1959;2:1049–53.
284. Fischer JA, Schmid M. Treatment of primary biliary cirrhosis with azothioprine. Lancet 1967;1:421–4.
285. Arcon-Segovia D, Mayorga-Cortes A, Wolpert E. Primary biliary cirrhosis. Prompt relief of pruritus with azathioprine treatment. JAMA 1970;214:367–8.
286. Schworer H, Hartmann H, Ramadori G. Relief of cholestatic pruritus by a novel class of drugs: 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists: effectiveness of ondansetron. Pain 1995;61:33–7.
287. Borgeat A, Wilder-Smith OH, Mentha G. Subhypnotic doses of propofol relieve pruritus associated with liver disease. Gastroenterology 1993;104:244–7.
288. Witt-Sullivan H, Heathcote J, Cauch K, et al. The demography of primary biliary cirrhosis in Ontario, Canada. Hepatology 1990;12:98–105.
289. Cauch-Dudek K, Abbey S, Stewart D, Heathcote EJ. Fatigue and quality of life in primary biliary cirrhosis. Hepatology 1995; 22:108A. 291.
290. Swain MG, Maric M. Defective corticotropin-releasing hormone mediated neuroendocrine and behavioral responses in cholestatic rats: implications for cholestatic liver disease-related sickness behaviors. Hepatology 1995;22:1560–4.
291. Swain MG, Maric M. Improvement in cholestasis-associated fatiguewith a serotonin receptor agonist using a novel rat model of fatigue assessment. Hepatology 1997;25:291–4.
292. Bergasa NV, Vergalla J, Turner ML, et al. Alpha-melanocytestimulating hormonein primary biliary cirrhosis. Ann NYAcad Sci 1993;680:454–8.
293. Sokol RJ, Devereaux M, Khandwala RA. Effect of dietary lipid and vitamin E on mitochondrial lipid peroxidation and hepatic injury in the bile duct-ligated rat. J Lipid Res 1991;32: 1349–57.
294. Jones EA. Relief from profound fatigue associated with chronic liver disease by long-termondansetron therapy. Lancet 1999;354:397.
295. Sabesin SM. Cholestatic lipoproteins –their pathogenesis and significance. Gastroenterology 1982;83:704–9.
296. Seidel D. Lipoproteins in liver disease. J Clin Chem Clin Biochem 1987;25:541–51.
297. Alagille D, Estrada A, Hadchouel M, et al. Syndromic paucity of interlobular bile ducts (Alagille syndrome or arteriohepatic dysplasia): review of 80 cases. J Pediatr 1987;110:195–200.
298. Sokol RJ. Medical management of neonatal cholestasis. In: Balistreri WF, Stocker J, eds. Pediatric hepatology. Philadelphia: Hemisphere Publishing, 1990:41–76.
299. Thannhauser SJ. Hypercholesterolemic zanthomatosis secondary to liver disease. Lipidosis. New York: Oxford University Press, 1950:143.
300. Crippin JS, Lindor KD, Jorgensen R, et al. Hypercholesterolemia and atherosclerosis in primary biliary cirrhosis: what is the risk? Hepatology 1992;15:858–62.
301. Shepherd J, Packard CJ, Bicker S, et al. Cholestyramine promotes receptor-mediated low-density-lipoprotein catabolism. N Engl J Med 1980;302:1219–22.
302. Schaffner F, Klion FM, Latuff AJ. The long term use of cholestyramine in the treatment of primary biliary cirrhosis. Gastroenterology 1965;48:293–8.
303. Armstrong MJ, Carey MC. The hydrophobic-hydrophilic balance of bile salts. Inverse correlation between reverse-phase high performance liquid chromatographic mobilities and micellar cholesterol-solubilizing capacities. J Lipid Res 1982;23:70–80.
304. Carulli N, Loria P, Bertolotti M, et al. Effects of acute changes of bile acid pool composition on biliary lipid secretion. J Clin Invest 1984;74:614–24.
305. Fromm H. Bile acid-lipoprotein interactions: effects of ursodeoxycholic acid (ursodiol). Dig Dis Sci 1989;34(12 suppl): 21S–23S.
306. Hawton K, Fagg J, Marsack P. Association between epilepsy and attempted suicide. JNeurol Neurosurg Psychiatry 1980;43:168–70.
307. Balistreri WF, A-Kader H, Heubi JE, et al. UDCA decreases serum cholesterol levels, ameliorates symptoms and improves biochemical parameters in pediatric patients w/chronic intrahepatic cholestasis. Gastroenterology 1990;96:A566.
308. Mol MJ, Erkelens DW, Leuven JA, et al. Effects of synvinolin (MK-733) on plasma lipids in familial hypercholesterolaemia. Lancet 1986;2:936–9.
309. Grundy SM. HMG-Co A reductase inhibitors for treatment of hypercholesterolemia. N Engl J Med 1988;319:24–33.
310. Duane WC, Hunninghake DB, Freeman ML, et al. Simvastatin, a competitive inhibitor of HMG-Co A reductase, lowers cholesterol saturation index of gallbladder bile. Hepatology 1988;8:1147–50.
311. Logan GM, Duane WC. Lovastatin added to ursodeoxycholic acid further reduces biliary cholesterol saturation. Gastroenterology 1990;98:1572–6.
312. Mazzella G, Parini P, Festi D, et al. Effect of simvastatin, ursodeoxycholic acid and simvastatin plus ursodeoxycholic acid on biliary lipid secretion and cholic acid kinetics in nonfamilial hypercholesterolemia. Hepatology 1992;15:1072–8.
313. Linarelli LG, Hengstenberg FH, Drash AL. Effect of phenobarbital on hyperlipemia in patients with intrahepatic and extrahepatic cholestasis. J Pediatr 1973;83:291–8.
314. Becker M, von Bergmann K, Rotthauwe HW, Leiss O. Effects of phenobarbital on biliary lipid metabolism in children with chronic intrahepatic cholestasis. Eur J Pediatr 1984;143:41–44.
315. Matsubara S, Abe Y, Blasutig E, et al. Treatment for cholestatic liver disease (CLD): plasma sorption and filtration for improved bilirubin removal. Trans Am Soc Artif Intern Organs 1983;29:693–7.
316. Buchwald H, Fitch L, Campos C. Partial ileal bypass in the treatment of hypercholesterolemia. J Fam Practice 1992;35:69–76.
317. Hollands CM, Rivera-Pedrogo FJ, Gonzalez-Vallina R, et al. Ileal exclusion for Byler’s disease: an alternative surgical approach with promising early results for pruritus. J Pediatr Surg 1998; 33:220–4.
318. Emerick KM, Whitington PF. Partial external biliary diversion for intractable pruritus and xanthomas in Alagille syndrome. Hepatology 2002;35:1501–6.
319. Buckley DA, Higgins EM, du Vivier AW. Resolution of xanthomas in Alagille syndrome after liver transplantation. Pediatr Dermatol 1998;15:199–202.
320. Cardona J, Houssin D, Gauthier F, et al. Liver transplantation in children with Alagille syndrome –a study of twelve cases. Transplantation 1995;60:339–42.
321. Watkins J. Fat digestion in cholestasis. In: Adcock EI, Lester R, eds. Neonatal cholestasis: causes, syndromes, therapies. Report of the 87th Ross Conference in Pediatric Research. Columbus, OH: Ross Laboratories, 1984:94.
322. Badley BW, Murphy GM, Bouchier IA, Sherlock S. Diminished micellar phase lipid in patients with chronic nonalcoholic liver disease and steatorrhea. Gastroenterology 1970;58:781–9.
323. Freund H, Dienstag J, Lehrich J, et al. Infusion of branchedchain enriched amino acid solution in patients with hepatic encephalopathy. Ann Surg 1982;196:209–20.
324. Weisdorf SA, Freese DK, Fath JJ, et al. Amino acid abnormalities in infants with extrahepatic biliary atresia and cirrhosis. J Pediatr Gastroenterol Nutr 1987;6:860–4.
325. Devenyi AG, Barron TF, Mamourian AC. Dystonia, hyperintense basal ganglia, and high whole blood manganese levels in Alagille’s syndrome. Gastroenterology 1994;106:1068–71.
326. Goulet OJ, de Ville de GJ, Otte JB, Ricour C. Preoperative nutritional evaluation and support for liver transplantation in children. Transplant Proc 1987;19:3249–55.
327. Pierro A, Koletzko B, Carnielli V, et al. Resting energy expenditure is increased in infants and childrenwith extrahepatic biliary atresia. J Pediatr Surg 1989;24:534–8.
328. O’Keefe SJ, El-Zayadi AR, Carraher TE, et al. Malnutrition and immuno-incompetence in patients with liver disease. Lancet 1980;2(8195 pt 1):615–17.
329. Kaufman SS, Murray ND, Wood RP, et al. Nutritional support for the infant with extrahepatic biliary atresia. J Pediatr 1987;110:679–86.
330. Bucuvalas JC, Cutfield W, Horn J, et al. Resistance tothe growthpromoting and metabolic effects of growth hormonein children with chronic liver disease. J Pediatr 1990;117:397–402.
331. Maes M, Sokal E, Otte JB. Growth factors in children with endstage liver disease before and after liver transplantation: a review. Pediatr Transplant 1997;1:171–5.
332. Holt RI, Baker AJ, Jones JS, Miell JP. The insulin-like growth factor and binding protein axis in children with end-stage liver disease before and after orthotopic liver transplantation. Pediatr Transplant 1998;2:76–84.
333. Holt RI, Baker AJ, Miell JP. The pathogenesis of growth failure in paediatric liver disease. J Hepatol 1997;27:413–23.
334. Greer RM, Quirk P, Cleghorn GJ, Shepherd RW. Growth hormone resistance and somatomedins in children with end-stage liver disease awaiting transplantation. J Pediatr Gastroenterol Nutr 1998;27:148–54.
335. Sokol RJ, Stall C. Anthropometric evaluation of children with chronic liver disease. Am J Clin Nutr 1990;52:203–8.
336. Stewart SM, Uauy R, Kennard BD, et al. Mental development and growth in children with chronic liver disease of early and late onset. Pediatrics 1988;82:167–72.
337. Stewart SM, Uauy R, Waller DA, et al. Mental and motor development, social competence, andgrowth one year after successful pediatric liver transplantation. J Pediatr 1989;114(4 pt 1):574–81.
338. Wayman KI, Cox KL, Esquivel CO. Neurodevelopmental outcome of young children with extrahepatic biliary atresia 1 year after liver transplantation. J Pediatr 1997;131:894–8.
339. Merritt RJ, Suskind RM. Nutritional survey of hospitalized pediatric patients. Am J Clin Nutr 1979;32:1320–5.
340. Hehir DJ, Jenkins RL, Bistrian BR, Blackburn GL. Nutrition in patients undergoing orthotopic liver transplant. JPENJParenter Enteral Nutr 1985;9:695–700.
341. Tuten MB, Wogt S, Dasse F, Leider Z. Utilization of prealbumin as a nutritional parameter. JPEN J Parenter Enteral Nutr 1985;9:709–11.
342. Meritt R, Blackburn G. In: Suskind R, ed. Textbook of pediatric nutrition. New York: Raven, 1981:294.
343. Moreno LA, Gottrand F, Hoden S, et al. Improvement of nutritional status in cholestatic children with supplemental nocturnal enteral nutrition. J Pediatr Gastroenterol Nutr 1991;12:213–16.
344. Smith J, Horowitz J, Henderson JM, Heymsfield S. Enteral hyperalimentation in undernourished patients with cirrhosis and ascites. Am J Clin Nutr 1982;35:56–72.
345. Fuchs IG. Enteral support of the hospitalized child. In: Suskind R, Lewinter-Suskind L, eds. Textbook of pediatricnutrition. 2nd ed. New York: Raven, 1993:239–48.
346. Parker P, Stroop S, Greene H. A controlled comparison of continuous versus intermittent feeding in the treatment of infants with intestinal disease. J Pediatr 1981;99:360–4.
347. Ferry GD, Selby M, Pietro TJ. Clinical response to short-term nasogastric feeding in infants with gastroesophageal reflux and growth failure. J Pediatr Gastroenterol Nutr 1983;2:57–61.
348. Weber A, Roy CC. The malabsorption associated with chronic liver disease in children. Pediatrics 1972;50:73–83.
349. Cohen MI, Gartner LM. The use of medium-chain triglycerides in the management of biliary atresia. J Pediatr 1971;79: 379–84.
350. Sokal EM, Baudoux MC, Collette E, et al. Branched chain amino acids improve body composition and nitrogen balance in a rat model of extra hepatic biliary atresia. Pediatr Res 1996;40:66–71.
351. Chin SE, Shepherd RW, Thomas BJ, et al. Nutritional support in children with end-stage liver disease: a randomized crossover trial of a branched-chain amino acid supplement. Am J Clin Nutr 1992;56:158–63.
352. Charlton CP, Buchanan E, Holden CE, et al. Intensive enteral feeding in advanced cirrhosis: reversal of malnutrition without precipitation of hepatic encephalopathy. Arch Dis Child 1992;67:603–7.
353. Wene JD, Connor WE, Den Besten L. The development of essential fatty acid deficiency in healthy men fed fat-free diets intravenously and orally. J Clin Invest 1975;56:127–34.
354. Marcus AJ. The role of lipids in platelet function: with particular reference to the arachidonic acid pathway. J Lipid Res 1978;19:793–826.
355. Barr LH, Dunn GD, Brennan MF. Essential fatty acid deficiency during total parenteral nutrition. Ann Surg 1981;193:304–11.
356. Hansen A, Wiese H, Boelshe A, et al. Role of linoleic acid in infant nutrition. Pediatr 1963;31:171–92.
357. Caldwell MD, Jonsson HT, Othersen HB Jr. Essential fatty acid deficiency in an infant receiving prolonged parenteral alimentation. J Pediatr 1972;81:894–8.
358. Clandinin MT, Chappell JE, Heim T, et al. Fatty acid utilization in perinatal de novo synthesis of tissues. Early Hum Dev 1981;5:355–66.
359. Swart G, Frenkel M, Van der Berg J. Minimum protein requirements in advanced liver disease: a metabolic ward study of the effects of BCAA. In: Walser M, Williamson R, eds. Metabolism and clinical implications of branched chain amino and ketoacids. New York: Elsevier North Holland, 1981:427–32.
360. Holman R. EFA deficiency in humans. In: Rechcigl M, ed. CRC handbook series in nutrition and food: section E, nutritional disorders. West Palm Beach, FL: CRC Press, 1978:335–68.
361. Gourley GR, Farrell PM, Odell GB. Essential fatty acid deficiency after hepatic portoenterostomy for biliary atresia. Am J Clin Nutr 1982;36:1194–9.
362. Miyano T, Yamashiro Y, Shimizu T, et al. Essential fatty acid deficiency in congenital biliary atresia: successful treatment to reverse deficiency. J Pediatr Surg 1986;21:277–81.
363. Pettei MJ, Daftary S, Levine JJ. Essential fatty acid deficiency associated with the use of a medium-chain-triglyceride infant formula in pediatric hepatobiliary disease. Am J Clin Nutr 1991;53:1217–21.
364. Socha P, Koletzko B, Swiatkowska E, et al. Essential fatty acid metabolism in infants with cholestasis. Acta Paediatr 1998;87: 278–83.
365. Thompson G. Absorption of fat-soluable vitamins and sterols. J Clin Pathol 1971;24(suppl 5):85.
366. Book L. Fat soluble vitamins in cholestasis. In: Adcock EI, Lester R, eds. Neonatal cholestasis: causes, syndromes, therapies. Report of the Eighty-Seventh Ross Conference in Pediatric Research. Columbus, OH: Ross Laboratories, 1984:104–10.
367. The National Research Council Recommended Dietary Allowances. 10th ed. Washington, DC:National Research Council, 1989.
368. Blomhoff R, Wake K. Perisinusoidal stellate cells of the liver: important roles in retinol metabolism and fibrosis. FASEB J 1991;5:271–7.
369. Andrews WS, Pau CM, Chase HP, et al. Fat soluble vitamin deficiency in biliary atresia. J Pediatr Surg 1981;16:284–90.
370. Chin SE, Shepherd RW, Thomas BJ, 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.
371. Amedee-Manesme O, Furr HC, Alvarez F, et al. Biochemical indicators of vitamin A depletion in children with cholestasis. Hepatology 1985;5:1143–8.
372. Mobarhan S, Russell RM, Underwood BA, et al. Evaluation of the relative dose response test for vitamin A nutriture in cirrhotics. Am J Clin Nutr 1981;34:2264–70.
373. McClain CJ, Van Thiel DH, Parker S, et al. Alterations in zinc, vitamin A, and retinol-binding protein in chronic alcoholics: a possible mechanism for night blindness and hypogonadism. Alcohol Clin Exp Res 1979;3:135–41.
374. Mourey MS, Siegenthaler G, Amedee-Manesme O. Regulation of metabolism of retinol-binding protein by vitamin A status in children with biliary atresia. Am J Clin Nutr 1990;51:638–43.
375. Amedee-Manesme O, Mourey MS, Hanck A, Therasse J. Vitamin A relative dose response test: validation by intravenous injection in children with liver disease. Am J Clin Nutr 1987;46: 286–9.
376. Ong DE, Amedee-Manesme O. Liver levels of vitamin A and cellular retinol-binding protein for patients with biliary atresia. Hepatology 1987;7:253–6.
377. Carlier C, Coste J, Etchepare M, Amedee-Manesme O. Conjunctival impression cytology with transfer as a field-applicable indicator of vitamin Astatus for mass screening. Int J Epidemiol 1992;21:373–80.
378. Natadisastra G, Wittpenn JR, West KP Jr, et al. Impression cytology for detection of vitamin A deficiency. Arch Ophthalmol 1987;105:1224–8.
379. Sommer A, Sugana T. Corneal xerophthalmia and keratomalacia. Arch Ophthalmol 1982;100:404–11.
380. Solomons NW, Russell RM, Vinton E, et al. Application of a rapid dark adaptation test in children. J Pediatr Gastroenterol Nutr 1982;1:571–4.
381. Russell RM, Iber FL, Krasinski SD, Miller P. Protein-energy malnutrition and liver dysfunction limit the usefulness of the relative dose response (RDR) test for predicting vitamin A deficiency. Hum Nutr Clin Nutr 1983;37:361–71.
382. Feranchak AP, Gralla J, King R, et al. Comparison of indices of vitamin A status in children with chronic liver disease. Hepatology 2005;42:782–92.
383. Scheffer C, Tseng G. Staging of conjunctival squamous metaplasia by impression cytology. J Ophthalmol 1985;92:728–33.
384. Amedee-Manesme O, Luzeau R, Wittepen JR, et al. Impression cytology detects subclinical vitamin A deficiency. Am J Clin Nutr 1988;47:875–8.
385. Kjolhede CL, Gadomski AM, Wittpenn J, et al. Conjunctival impression cytology: feasibility of a field trial to detect subclinical vitamin A deficiency. Am J Clin Nutr 1989;49:490–4.
386. Gadomski AM, Kjolhede CL, Wittpenn J, et al. Conjunctival impression cytology (CIC) to detect subclinical vitamin A deficiency: comparison of CIC with biochemical assessments. Am J Clin Nutr 1989;49:495–500.
387. Feranchak A, Ramirez R, Shivaram K, et al. Assessment of vitamin A status in children with cholestasis liver disease using a modified oral relative dose response test. J Pediatr Gastro and Nutr 1996;23:A351.
388. Balistreri WF. Neonatal cholestasis. J Pediatr 1985;106:171–84.
389. Sokol RJ, Johnson KE, Karrer FM, et al. Improvement of cyclosporin absorption in children after liver transplantation by means of water-soluble vitamin E. Lancet 1991;338:212–14.
390. Argao EA, Heubi JE, Hollis BW, Tsang RC. d-Alpha-tocopheryl polyethylene glycol-1000 succinate enhances the absorption of vitamin D in chronic cholestatic liver disease of infancy and childhood. Pediatr Res 1992;31:146–50.
391. Russell RM, Boyer JL, Bagheri SA, Hruban Z. Hepatic injury from chronic hypervitaminosis a resulting in portal hypertension and ascites. N Engl J Med 1974;291:435–40.
392. Geubel AP, De Galocsy C, Alves N, et al. Liver damage caused by therapeutic vitamin A administration: estimate of dose-related toxicity in 41 cases. Gastroenterology 1991 Jun;100:1701–9.
393. Minuk GY, Kelly JK, Hwang WS. Vitamin A hepatotoxicity in multiple family members. Hepatology 1988;8:272–5.
394. Rubin E, Florman AL, Degnan T, Diaz J. Hepatic injury in chronic hypervitaminosis A. Am J Dis Child 1970;119:132–8.
395. Lippe B, Hensen L, Mendoza G, et al. Chronic vitamin A intoxication. A multisystem disease that could reach epidemic proportions. Am J Dis Child 1981;135:634–6.
396. Oliver TK Jr. Chronic vitamin A intoxication; report of a case in an older child and review of the literature. AMA J Dis Child 1958;95(1 part 1):57–68.
397. Mahoney CP, Margolis MT, Knauss TA, Labbe RF. Chronic vitamin A intoxication in infants fed chicken liver. Pediatrics 1980;65:893–7.
398. Fisher G, Skillern PG. Hypercalcemia due to hypervitaminosis A. JAMA 1974;227:1413–14.
399. Frame B, Jackson CE, Reynolds WA, Umphrey JE. Hypercalcemia and skeletal effects in chronic hypervitaminosis A. Ann Intern Med 1974;80:44–8.
400. Smith FR, Goodman DS. Vitamin Atransport inhumanvitamin A toxicity. N Engl J Med 1976;294:805–8.
401. Heubi JE, Hollis BW, Specker B, Tsang RC. Bone disease in chronic childhood cholestasis. I. Vitamin D absorption and metabolism. Hepatology 1989;9:258–64.
402. Skinner R, Long R, Sherlock S, Willis M. 25hydroxylation of vitamin D in PBC. Lancet 1972;1:720–1.
403. Plourde V, Gascon-Barre M, Willems B, Huet PM. Severe cholestasis leads to vitamin D depletion without perturbing its C-25 hydroxylation in the dog. Hepatology 1988;8:1577–85.
404. Bouillon R, Reynaert J, Claes JH, et al. The effect of anticonvulsant therapy on serum levels of 25-hydroxy-vitamin D, calcium, and parathyroid hormone. J Clin Endocrinol Metab 1975;41:1130–5.
405. Holda ME, Ryan JR. Hepatobiliary rickets. J Pediatr Orthop 1982;2:285–7.
406. Roberts C, Book L, Chan G, et al. Rickets in children with cholestatic liver disease: evaluation and treatment. Pediatr Res 1981;15:544.
407. Bucuvalas JC, Heubi JE, Specker BL, et al. Calcium absorption in bone disease associated with chronic cholestasis during childhood. Hepatology 1990;12:1200–5.
408. Heubi JE, Higgins JV, Argao EA, et al. 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.
409. Heubi JE, Tsang RC, Steichen JJ, et al. 1, 25-Dihydroxyvitamin D3 in childhood hepatic osteodystrophy. J Pediatr 1979;94:977–82.
410. Vleggaar FP, Van Buuren HR, Wolfhagen FH, et al. Prevention and treatment of osteoporosis in primary biliary cirrhosis. Eur J Gastroenterol Hepatol 1999;11:617–21.
411. Norman A, Miller B. Vitamin D. In:Machlin J, ed. Handbook of vitamins—nutritional, biochemical and clinical aspects. New York: Marcel-Dekker, Inc., 1984:45–98.
412. Sokol RJ, Heubi JE, Iannaccone S, et al. Mechanism causing vitamin E deficiency during chronic childhood cholestasis. Gastroenterology 1983;85:1172–82.
413. Traber MG, Olivecrona T, Kayden HJ. Bovine milk lipoprotein lipase transfers tocopherol to human fibroblasts during triglyceride hydrolysis in vitro. J Clin Invest 1985;75:1729–34.
414. Traber MG, Kayden HJ. Vitamin E is delivered to cells via the high affinity receptor for low-density lipoprotein. Am J Clin Nutr 1984;40:747–51.
415. Guggenheim MA, Jackson V, Lilly J, Silverman A. Vitamin E deficiency and neurologic disease in children with cholestasis: a prospective study. J Pediatr 1983;102:577–9.
416. Sokol RJ, Guggenheim MA, Heubi JE, et al. Frequency and clinical progression of the vitamin E deficiency neurologic disorder in children with prolonged neonatal cholestasis. Am JDis Child 1985;139:1211–15.
417. Sokol RJ, Guggenheim MA, Iannaccone ST, et al. Improved neurologic function after long-term correction of vitamin E deficiency in children with chronic cholestasis. N Engl J Med 1985;313:1580–6.
418. Sokol RJ. Vitamin E deficiency and neurologic disease. Annu Rev Nutr 1988;8:351–73.
419. Rosenblum JL, Keating JP, Prensky AL, Nelson JS. A progressive neurologic syndrome in children with chronic liver disease. N Engl J Med 1981;304:503–8.
420. Sokol RJ, Bove KE, Heubi JE, Iannaccone ST. Vitamin E deficiency during chronic childhood cholestasis: presence of sural nerve lesion prior to 2 1/2 years of age. J Pediatr 1983;103:197–204.
421. Stewart SM, Uauy R, Waller DA, et al. Mental and motor development correlates in patients with end-stage biliary atresia awaiting liver transplantation. Pediatrics 1987;79:882–8.
422. Satel SL, Riely CA. Vitamin E deficiency and neurologic dysfunction in children. N Engl J Med 1986;314:1389–90.
423. Arria AM, Tarter RE, Warty V, Van Thiel DH. Vitamin E deficiency and psychomotor dysfunction in adults with primary biliary cirrhosis. Am J Clin Nutr 1990;52:383–90.
424. Alvarez F, Landrieu P, Feo C, et al. Vitamin E deficiency is responsible for neurologic abnormalities in cholestatic children. J Pediatr 1985;107:422–5.
425. Oski FA, Barness LA. Vitamin E deficiency: a previously unrecognized cause of hemolytic anemia in the premature infant. J Pediatr 1967;70:211–20.
426. Tappel A. Vitamin E as the biological lipid antioxidant. Vitam Horm 1962;20:493–510.
427. Burton GW, Joyce A, Ingold KU. Is vitamin E the only lipid-soluble, chain-breaking antioxidant in human blood plasma and erythrocyte membranes? Arch Biochem Biophys 1983;221:281–90.
428. Traber MG. Vitamin E, nuclear receptors and xenobiotic metabolism. Arch Biochem Biophys 2004;423:6–11.
429. Sokol RJ, Devereaux M, Mierau GW, et al. Oxidant injury to hepatic mitochondrial lipids in rats with dietary copper overload. Modification by vitamin E deficiency. Gastroenterology 1990;99:1061–71.
430. Sokol R, Harris R, Heubi J. Effect of vitamin E on neutrophil chemotasis in chronic childhood cholestasis. Hepatology 1984;4:1048.
431. Kowdley KV, Mason JB, Meydani SN, et al. Vitamin E deficiency and impaired cellular immunity related to intestinal fat malabsorption. Gastroenterology 1992;102:2139–42.
432. Horwitt MK, Harvey CC, Dahm CHJr, Searcy MT. Relationship between tocopherol and serum lipid levels for determination of nutritional adequacy. Ann N Y Acad Sci 1972;203:223–36.
433. Sokol RJ, Heubi JE, Iannaccone ST, et al. Vitamin E deficiency with normal serum vitamin E concentrations in children with chronic cholestasis. N Engl J Med 1984;310:1209–12.
434. Farrell PM, Levine SL, Murphy MD, Adams AJ. Plasma tocopherol levels and tocopherol-lipid relationships in a normal population of children as compared to healthy adults. Am J Clin Nutr 1978;31:1720–6.
435. Gordon HH, Nitowsky HM, Cornblath M. Studies of tocopherol deficiency in infants and children. I. Hemolysis of erythrocytes in hydrogen peroxide. AMA Am J Dis Child 1955;90:669–81.
436. Cynamon HA, Isenberg JN, Nguyen CH. Erythrocyte malondialdehyde release in vitro: a functional measure of vitamin E status. Clin Chim Acta 1985;151:169–76.
437. Sokol RJ, Butler-Simon N, Conner C, et al. Multicenter trial of d-alpha-tocopherylpolyethylene glycol 1000 succinate for treatment of vitamin E deficiency in children with chronic cholestasis. Gastroenterology 1993;104:1727–35.
438. Bendich A, Machlin LJ. Safety of oral intake of vitamin E. Am J Clin Nutr 1988;48:612–19.
439. Farrell PM, Bieri JG. Megavitamin E supplementation in man. Am J Clin Nutr 1975;28:1381–6.
440. Corrigan JJ Jr, Marcus FI. Coagulopathy associatedwith vitamin E ingestion. JAMA 1974;230:1300–1.
441. Corrigan JJ Jr. The effect of vitamin E on warfarin-induced vitamin K deficiency. Ann N Y Acad Sci 1982;393:361–8.
442. Johnson L, Bowen FW Jr, Abbasi S, et al. Relationship of prolonged pharmacologic serum levels of vitamin E to incidence of sepsis and necrotizing enterocolitis in infants with birth weight 1, 500 grams or less. Pediatrics 1985;75:619–38.
443. Lorch V, Murphy D, Hoersten LR, et al. Unusual syndrome among premature infants: association with a new intravenous vitamin E product. Pediatrics 1985;75:598–602.
444. Suttie J. Vitamin K. In: Diplock A, ed. Fat soluble vitamins. Lancaster, PA: Technomic Publishing Co., 1985:225.
445. Olson RE. The function and metabolism of vitamin K. Annu Rev Nutr 1984;4:281–337.
446. Shah DV, Suttie JW. The vitamin K dependent, in vitro production of prothrombin. Biochem Biophys Res Commun 1974;60:1397–402.
447. Price PA, Williamson MK, Lothringer JW. Origin of the vitamin K-dependent bone protein found in plasma and its clearance by kidney and bone. J Biol Chem 1981;256:12760–6.
448. Price PA, Parthemore JG, Deftos LJ. New biochemical marker for bone metabolism. Measurement by radioimmunoassay of bone GLA protein in the plasma of normal subjects and patients with bone disease. J Clin Invest 1980;66:878–83.
449. Vermeer C, Knapen MH, Schurgers LJ. Vitamin Kand metabolic bone disease. J Clin Pathol 1998;51:424–6.
450. Feskanich D, Weber P, Willett WC, et al. Vitamin K intake and hip fractures in women: a prospective study. Am J Clin Nutr 1999;69:74–9.
451. Verity C, Carswell F, Scott G. Vitamin K deficiency causing infantile intracranial hemorrhage after the neonatal period. Lancet 1983;1:1439–40.
452. Bancroft J, Cohen MB. Intracranial hemorrhage due to vitamin K deficiency in breast-fed infants with cholestasis. J Pediatr Gastroenterol Nutr 1993;16:78–80.
453. Yanofsky RA, Jackson VG, Lilly JR, et al. The multiple coagulopathies of biliary atresia. Am J Hematol 1984;16:171–80.
454. Lane PA, Hathaway WE. Vitamin K in infancy. J Pediatr 1985;106: 351–9.
455. Silverman A, Roy C. Pediatric clinical gastroenterology. St. Louis: C. V. Mosby, 1983:526.
456. Zinkham WH. Peripheral blood and bilirubin values in normal full-term primaquine-sensitive Negro infants: effect of vitamin K. Pediatrics 1963;31:983–95.
457. Rossouw JE, Labadarios D, Davis M, Williams R. Water-soluble vitamins in severe liver disease. S Afr Med J 1978;54:183–6.
458. Goksu N, Ozsoylu S. Hepatic and serum levels of zinc, copper, and magnesium in childhood cirrhosis. J Pediatr Gastroenterol Nutr 1986;5:459–62.
459. Cohen MI, Mc Namara H, Finberg L. Serummagnesium in children with cirrhosis. J Pediatr 1970;76:453–5.
460. Kaya G, Ozsoylu S. Serum magnesium levels in children with cirrhosis. Acta Paediatr Scand 1972;161:442–4.
461. Stutzman FL, Matuzio DS. Blood serum magnesium in portal cirrhosis and diabetes mellitus. J Lab Clin Med 1953;41:215–19.
462. Zelikovic I, Dabbagh S, Friedman AL, et al. Severe renal osteodystrophy without elevated serum immunoreactive parathyroid hormone concentrations in hypomagnesemia due to renal magnesium wasting. Pediatrics 1987;79:403–9.
463. Wiegmann T, Kaye M. Hypomagnesemic hypocalcemia. Early serum calcium and late parathyroid hormone increase with magnesium therapy. Arch Intern Med 1977;137:953–5.
464. Anast CS, Winnacker JL, Forte LR, Burns TW. Impaired release of parathyroid hormone in magnesium deficiency. J Clin Endocrinol Metab 1976;42:707–17.
465. Rude RK, Oldham SB, Sharp CF Jr, Singer FR. Parathyroid hormone secretion in magnesium deficiency. J Clin Endocrinol Metab 1978;47:800–6.
466. Duran MJ, Borst GC 3rd, Osburne RC, Eil C. Concurrent renal hypomagnesemia and hypoparathyroidism with normal parathormone responsiveness. Am J Med 1984;76:151–4.
467. Ralston S, Boyle IT, Cowan RA, et al. PTH and vitamin D responses during treatment of hypomagnesaemic hypoparathyroidism. Acta Endocrinol (Copenh) 1983;103:535–8.
468. Rude RK, Adams JS, Ryzen E, et al. Low serum concentrations of 1, 25-dihydroxyvitamin D in human magnesium deficiency. J Clin Endocrinol Metab 1985;61:933–40.
469. Medalle R, Waterhouse C, Hahn TJ. Vitamin D resistance in magnesium deficiency. Am J Clin Nutr 1976;29:854–8.
470. Hambidge KM, Krebs NF, Lilly JR, Zerbe GO. Plasma and urine zinc in infants and children with extrahepatic biliary atresia. J Pediatr Gastroenterol Nutr 1987;6:872–7.
471. Committee on Nutrition. Zinc. Pediatrics 1978;62:408–12.
472. Narkewicz MR, Krebs N, Karrer F, et al. Correction of hypozincemia following liver transplantation in children is associated with reduced urinary zinc loss. Hepatology 1999;29:830–3.
473. Litov RE, Combs GF Jr. Selenium in pediatric nutrition. Pediatrics 1991;87:339–51.
474. Collipp PJ, Chen SY. Cardiomyopathy and selenium deficiency in a two-year-old girl. N Engl J Med 1981;304:1304–5.
475. Fleming CR, Lie JT, McCall JT, et al. Selenium deficiency and fatal cardiomyopathy in a patient on home parenteral nutrition. Gastroenterology 1982;83:689–93.
476. Brown MR, Cohen HJ, Lyons JM, et al. Proximal muscle weakness and selenium deficiency associated with long term parenteral nutrition. Am J Clin Nutr 1986;43:549–54.
477. Vinton NE, Dahlstrom KA, Strobel CT, Ament ME. Macrocytosis and pseudoalbinism: manifestations of selenium deficiency. J Pediatr 1987;111:711–17.
478. Hambidge K, Krebs N. Normal childhood nutrition and its disorders. In: Hathaway W, Hay W, Groothius J, Paisley J, eds. Current pediatric diagnosis and treatment. 11th ed. Norwalk, CT: Appleton & Lange, 1993:244.
479. Levander OA. The importance of selenium in total parenteral nutrition. Bull N Y Acad Med 1984;60:144–55.
480. Evans J, Newman S, Sherlock S. Liver copper levels in intrahepatic cholestasis of childhood. Gastroenterology 1978;75:875–8.
481. Benson GD. Hepatic copper accumulation in primary biliary cirrhosis. Yale J Biol Med 1979;52:83–8.
482. Hochstein P, Kumar KS, Forman SJ. Lipid peroxidation and the cytotoxicity of copper. Ann N Y Acad Sci 1980;355:240–8.
483. Jones M, Grand K, Perrault J, Dickson E. Clinical response to penicillamine in cholestatic liver disease. In: Daum F, ed. Extrahepatic biliary atresia. New York: Marcel-Dekker, 1983:227.
484. Evans J, Zerpa H, Nuttall L, et al. Copper chelation therapy in intrahepatic cholestasis of childhood. Gut 1983;24:42–8.
485. Dickson ER, Fleming TR, Wiesner RH, et al. Trial of penicillamine in advanced primary biliary cirrhosis. N Engl J Med 1985;312:1011–15.
486. Matloff DS, Alpert E, Resnick RH, Kaplan MM. A prospective trial of D-penicillamine in primary biliary cirrhosis. N Engl J Med 1982;306:319–26.
487. Sinatra R. Does total parenteral nutrition produce cholestasis? Neonatal cholestasis. Proceedings of the 87th Ross Conference on Pediatric Research. Columbus, OH: Ross Laboratories, 1984:85.
488. Farrell MK, Balistreri WF, Suchy FJ. Serum-sulfated lithocholate as an indicator of cholestasis during parenteral nutrition in infants and children. JPEN J Parenter Enteral Nutr 1982;6: 30–3.
489. Underwood E. Manganese. In: Underwood E (ed). Trace elements in human and animal nutrition. 4th ed. New York: Academic Press, 1977:170–95.
490. Bayliss EA, Hambidge KM, Sokol RJ, et al. Hepatic concentrations of zinc, copper and manganese in infantswith extrahepatic biliary atresia. J Trace Elem Med Biol 1995;9:40–3.
491. Plaa GL, de Lamirande E, Lewittes M, Yousef IM. Liver cell plasma membrane lipids in manganese-bilirubin-induced intrahepatic cholestasis. Biochem Pharmacol 1982;31:3698–701.
492. Fell JM, Reynolds AP, Meadows N, et al. Manganese toxicity in children receiving long-term parenteral nutrition. Lancet 1996;347:1218–21.
493. Spahr L, Butterworth RF, Fontaine S, et al. Increased blood manganese in cirrhotic patients: relationship to pallidal magnetic resonance signal hyperintensity and neurological symptoms. Hepatology 1996;24:1116–20.
494. Hauser RA, Zesiewicz TA, Martinez C, et al. Blood manganese correlates with brain magnetic resonance imaging changes in patients with liver disease. Can J Neurol Sci 1996;23:95–8.
495. Rose C, Butterworth RF, Zayed J, et al. Manganese deposition in basal ganglia structures results from both portalsystemic shunting and liver dysfunction. Gastroenterology 1999;117:640–4.
496. Morgan MY. Cerebral magnetic resonance imaging in patients with chronic liver disease. Metab Brain Dis 1998;13:273–90.
497. Layrargues GP, Rose C, Spahr L, et al. Role of manganese in the pathogenesis of portal-systemic encephalopathy. Metab Brain Dis 1998;13:311–17.
498. Krieger D, Krieger S, Jansen O, et al. Manganese and chronic hepatic encephalopathy. Lancet 1995;346:270–4.
499. Layrargues GP, Shapcott D, Spahr L, Butterworth RF. Accumulation of manganese and copper in pallidum of cirrhotic patients: role in the pathogenesis of hepatic encephalopathy? Metab Brain Dis 1995;10:353–6.
500. Ayotte P, Plaa GL. Biliary excretion in Sprague-Dawley and Gunn rats during manganese-bilirubin-induced cholestasis. Hepatology 1988;8:1069–78.
501. Hambidge KM, Sokol RJ, Fidanza SJ, Goodall MA. Plasma manganese concentrations in infants and children receiving parenteral nutrition. JPENJ Parenter Enteral Nutr 1989;13:168–71.
502. Kurkus J, Alcock NW, Shils ME. Manganese content of largevolume parenteral solutions and of nutrient additives. JPEN J Parenter Enteral Nutr 1984;8:254–7.
503. Malecki EA, Devenyi AG, Barron TF, et al. Iron and manganese homeostasis in chronic liver disease: relationship to pallidal T1- weighted magnetic resonance signal hyperintensity. Neurotoxicology 1999;20:647–52.
504. Klein GL, Alfrey AC, Miller NL, et al. Aluminumloading during total parenteral nutrition. Am J Clin Nutr 1982;35:1425–9.
505. Klein GL, Ott SM, Alfrey AC, et al. Aluminum as a factor in the bone disease of long-termparenteral nutrition. Trans Assoc Am Physicians 1982;95:155–64.
506. Popinska K, Kierkus J, Lyszkowska M, et al. Aluminumcontamination of parenteral nutrition additives, amino acid solutions, and lipid emulsions. Nutrition 1999;15:683–6.
507. Sedman AB, Klein GL, Merritt RJ, et al. Evidence of aluminum loading in infants receiving intravenous therapy. N Engl J Med 1985;312:1337–43.
508. Milliner DS, Shinaberger JH, Shuman P, Coburn JW. Inadvertent aluminum administration during plasma exchange due to aluminum contamination of albumin-replacement solutions. N Engl J Med 1985;312:165–7.
509. Klein G, Heyman M, Lee T, Alfrey A. Intravenous aluminum loading induces cholestasis. Hepatology 1986;6:1127.
510. Williams JW, Vera SR, Peters TG, et al. Biliary excretion of aluminum in aluminum osteodystrophy with liver disease. Ann Intern Med 1986;104:782–5.
511. Andersen KJ, Nordgaard K, Julshamn K, Schjoensby H. Increased serum aluminum in patients with jaundice. N Engl J Med 1979;301:728–9.
512. Burgess DB, Martin HP, Lilly JR. The developmental status of children undergoing the Kasai procedure for biliary atresia. Pediatrics 1982;70:624–9.
513. Bayley N. The value and limitation of infant testing. Children 1958;5:129.
514. Escalona SK, Moriarty A. Prediction of schoolage intelligence from infant tests. Child Dev 1961;32:597–605.
515. Thomas H. Someproblemsof studies concernedwith evaluating the predictive validity of infant tests. J Child Psychol Psychiatry 1967;8:197.
516. Lewis M, Mc Gurk H. Evaluation of infatn intelligence. Science 1972;178:1174.
517. Matheny R. Testing infant intelligence. Science 1973;182:734.
518. Conn H, Atterbury C. Cirrhosis. In: Schiff L, Schiff E, eds. Diseases of the liver. Philadelphia: JB Lippincott, 1987:725–864.
519. Potter C, Willis D, Sharp HL, Scharzenberg SJ. Primary and secondary amenorrhea associated with spironolactone therapy in chronic liver disease. J Pediatr 1992;121:141–3.
520. Rosenthal P, Ramos A, Mungo R. Management of children with hyperbilirubinemia and green teeth. J Pediatr 1986;108:103–5.
521. Eisenberg E. Anomalies of the teeth with stains and discolorations. J Prev Dent 1975;2:7–20.
522. Simon NB, Smith D. Living with chronic pediatric liver disease: the parents’ experience. Pediatr Nurs 1992;18:453–8, 489.