Bilirubin in clinical practice: A review

Liver International

Volumn 28, Issue 5, 2008, Pages 592-605

  Fevery, Johan ^a  

^a UNIVERSITY HOSPITALS LEUVEN   (Belgium)

Author keywords

Bilirubin; Cholestasis; Gilbert's syndrome; Glucuronyltransferase; Haemolysis

Indexed keywords

AMITRIPTYLINE; ATAZANAVIR; BILIRUBIN; GLUTETHIMIDE; KETOCONAZOLE; PHENOBARBITAL; RIFAMPICIN; SPIRONOLACTONE;

BILE SECRETION; BILIRUBIN BINDING; BILIRUBIN BLOOD LEVEL; BILIRUBIN METABOLISM; CARCINOGENESIS; CARDIOVASCULAR DISEASE; CHEMICAL STRUCTURE; CLINICAL PRACTICE; DRUG ACTIVITY; DYSERYTHROPOIESIS; GILBERT DISEASE; HUMAN; HYPERBILIRUBINEMIA; NEWBORN JAUNDICE; REVIEW;

BILIRUBIN; HUMANS; HYPERBILIRUBINEMIA; MOLECULAR STRUCTURE;

EID: 42149136735     PISSN: 14783223     EISSN: 14783231     Source Type: Journal    
DOI: 10.1111/j.1478-3231.2008.01716.x     Document Type: Review

References (106)

1. Tiribelli C, Ostrow JD. The molecular basis of bilirubin encephalopathy and toxicity: Report of an EASL Single Topic Conference. J Hepatol 2005; 43: 156-6.
2. Bonnett R, Davies JE, Hursthouse MB. Structure of bilirubin. Nature 1976; 262: 326-8.
3. Ostrow JD, Mukerjee P, Tiribelli C. Structure and binding of unconjugated bilirubin: Relevance for physiological and pathophysiological function. J Lipid Res 1994; 35: 1715-37.
4. Drummond GS, Kappas A. Chemoprevention of severe neonatal hyperbilirubinemia. Semin Perinatol 2004; 28: 365-8.
5. Aziz S, Kotal P, Leroy P, Servaes R, Eggermont E, Fevery J. Bilirubin-IXalpha and -IXbeta pigments, coproporphyrins and bile acids in meconium and stools from full-term and preterm neonates during the first month of life. Acta Paediatr 2001; 90: 81-7.
6. Blanckaert N, Fevery J, Heirwegh KP, Compernolle F. Characterization of the major diazo-positive pigments in bile of homozygous Gunn rats. Biochem J 1977; 164: 237-49.
7. Stoll MS, Vicker N, Gray CH, Bonnett R. Concerning the structure of photobilirubin II. Biochem J 1982; 201: 179-88.
8. Stoll MS, Zenone EA, Ostrow JD. Excretion of administered and endogenous photobilirubins in the bile of the jaundiced Gunn rat. J Clin Invest 1981; 68: 134-41.
9. Fevery J, Vanstapel F, Blanckaert N. Bile pigment metabolism. Baillieres Clin Gastroenterol 1989; 3: 283-312.
10. Berk PD, Howe RB, Bloomer JR, Berlin NI. Studies of bilirubin kinetics in normal adults. J Clin Invest 1969; 48: 2176-90.
11. Brodersen R. Bilirubin. Solubility and interaction with albumin and phospholipid. J Biol Chem 1979; 254: 2364-9.
12. Zucker SD, Goessling W, Hoppin AG. Unconjugated bilirubin exhibits spontaneous diffusion through model lipid bilayers and native hepatocyte membranes. J Biol Chem 1999; 274: 10852-62.
13. Mediavilla MG, Pascolo L, Rodriguez JV, Guibert EE, Ostrow JD, Tiribelli C. Uptake of [(3)H]bilirubin in freshly isolated rat hepatocytes: Role of free bilirubin concentration. FEBS Lett 1999; 463: 143-5.
14. Cui Y, König J, Leier I, Buchholz U, Keppler D. Hepatic uptake of bilirubin and its conjugates by the human organic anion transporter SLC21A6. J Biol Chem 2001; 276: 9626-30.
15. Campbell SD, de Morais SM, Xu JJ. Inhibition of human organic anion transporting polypeptide OATP 1B1 as a mechanism of drug-induced hyperbilirubinemia. Chem Biol Interact 2004; 150: 179-87.
16. Wang P, Kim RB, Chowdhury JR, Wolkoff AW. The human organic anion transport protein SLC21A6 is not sufficient for bilirubin transport. J Biol Chem 2003; 278: 20695-9.
17. Schachter D. Nature of the glucuronide in direct-reacting bilirubin. Science 1957; 126: 507-8.
18. Schmid R. Direct-reacting bilirubin, bilirubin glucuronide, in serum, bile and urine. Science 1956; 124: 76-7.
19. Billing BH, Cole PG, Lathe GH. The excretion of bilirubin as a diglucuronide giving the direct van den Bergh reaction. Biochem J 1957; 65: 774-84.
20. Talafant E. Properties and composition of the bile pigment giving a direct diazo reaction. Nature 1956; 178: 312.
21. Bosma PJ, Seppen J, Goldhoorn B, et al. Bilirubin UDP-glucuronosyltransferase 1 is the only relevant bilirubin glucuronidating isoform in man. J Biol Chem 1994; 269: 17960-4.
22. Huang W, Zhang J, Chua SS, et al. Induction of bilirubin clearance by the constitutive androstane receptor (CAR). Proc Natl Acad Sci USA 2003; 100: 4156-61.
23. Fevery J, Van de Vijver M, Michiels R, Heirwegh KP. Comparison in different species of biliary bilirubin-IX alpha conjugates with the activities of hepatic and renal bilirubin-IX alpha-uridine diphosphate glycosyltransferases. Biochem J 1977; 164: 737-46.
24. Jansen PL, Strautnieks SS, Jacquemin E, et al. Hepatocanalicular bile salt export pump deficiency in patients with progressive familial intrahepatic cholestasis. Gastroenterology 1999; 117: 1370-9.
25. Blanckaert N, Heirwegh KP, Compernolle F. Synthesis and separation by thin-layer chromatography of bilirubin-IX isomers. Their identification as tetrapyrroles and dipyrrolic ethyl anthranilate azo derivatives. Biochem J 1976; 155: 405-17.
26. Heirwegh KPM, Fevery J, Blanckaert N. Chromatographic analysis and structure determination of biliverdins and bilirubins. J Chrom 1989; 496: 1-26.
27. Fevery J. Experimentele studie van de glucuronidatiefunctie van de lever. Thesis for a Belgian Research Council Travel Grant, University of Leuven, 1996.
28. Nosslin B. The direct and indirect diazoreaction of bile pigments in serum. Scand J Clin Lab Invest 1960; 12 (Suppl. 49).
29. Fevery J, Claes J, Heirwegh K, De Groote J. Hyperbilirubinemia: significance of the ratio between direct-reacting and total bilirubin. Clin Chim Acta 1967; 17: 73-9.
30. Blanckaert N, Heirwegh KPM. Analysis and preparation of bilirubins and biliverdins. In: Ostrow JD., ed. Bile Pigments and Jaundice. New York: Marcel Dekker Inc., 1986; 38-79.
31. Blanckaert N. Analysis of bilirubin and bilirubin mono- and di-conjugates. Determination of their relative amounts in biological samples. Biochem J 1980; 185: 115-28.
32. Blanckaert N, Kabra PM, Farina FA, Stafford BE, Marton LJ, Schmid R. Measurement of bilirubin and its monoconjugates and diconjugates in human serum by alkaline methanolysis and high-performance liquid chromatography. J Lab Clin Med 1980; 96: 198-212.
33. Wickramasinghe SN, Wood WG. Advances in the understanding of the congenital dyserythropoietic anaemias. Br J Haematol 2005; 131: 431-46.
34. Glader B. Anemia: General consideration. Chapter 27. In: Greer JP, et al: Ed. Wintrobe's Clinical Hematology. Lippincott, Williams & Wilkins Co., 2004; 965-75.
35. Fevery J, Verwilghen R, Tan TG, De Groote J. Glucuronidation of bilirubin and the occurrence of pigment gallstones in patients with chronic haemolytic diseases. Eur J Clin Invest 1980; 10: 219-26.
36. Galanello R, Piras S, Barella S, et al. Cholelithiasis and Gilbert's syndrome in homozygous β thalassaemia. Br J Haematol 2001; 115: 926-8.
37. Bosma PJ, Chowdhury NR, Goldhoorn BG, et al. Sequence of exons and the flanking regions of human bilirubin-UDP-glucuronosyltransferase gene complex and identification of a genetic mutation in a patient with Crigler-Najjar syndrome, type I. Hepatology 1992; 15: 941-7.
38. Bosma PJ, Goldhoorn B, Oude Elferink RP, Sinaasappel M, Oostra BA, Jansen PL. A mutation in bilirubin uridine 5′-diphosphate-glucuronosyltransferase isoform 1 causing Crigler-Najjar syndrome type II. Gastroenterology 1993; 105: 216-20.
39. Seppen J, Bosma PJ, Goldhoorn BG, et al. Discrimination between Crigler-Najjar type I and II by expression of mutant bilirubin uridine diphosphate-glucuronosyltransferase. J Clin Invest 1994; 94: 2385-91.
40. Bosma PJ. Inherited disorders of bilirubin metabolism. J Hepatol 2003; 38: 107-17.
41. Takeuchi K, Kobayashi Y, Tamaki S, et al. Genetic polymorphisms of bilirubin uridine diphosphate-glucuronosyltransferase gene in Japanese patients with Crigler-Najjar syndrome or Gilbert's syndrome as well as in healthy Japanese subjects. J Gastroenterol Hepatol 2004; 19: 1023-8.
42. Bosma PJ, Chowdhury JR, Bakker C, et al. The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert's syndrome. N Engl J Med 1995; 333: 1171-5.
43. Raijmakers MT, Jansen PL, Steegers EA, Peters WH. Association of human liver bilirubin UDP-glucuronyltransferase activity with a polymorphism in the promoter region of the UGT1A1 gene. J Hepatol 2000; 33: 348-51.
44. Persico M, Persico E, Bakker CT, et al. Hepatic uptake of organic anions affects the plasma bilirubin level in subjects with Gilbert's syndrome mutations in UGT1A1. Hepatology 2001; 33: 627-32.
45. Ostanek B, Furlan D, Mavec T, Lukac-Bajalo J. UGT1A1(TA)n promoter polymorphism-a new case of a (TA)8 allele in Caucasians. Blood Cells Mol Dis 2007; 38: 78-82.
46. McDonagh AF, Palma LA. Hepatic excretion of circulating bilirubin photoproducts in the Gunn rat. J Clin Invest 1980; 66: 1182-5.
47. Ostrow JD, Pascolo L, Brites D, Tiribelli C. Molecular basis of bilirubin-induced neurotoxicity. Trends Mol Med 2004; 10: 65-70.
48. 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: 306-31.
49. van der Veere CN, Sinaasappel M, McDonagh AF, et al. Current therapy for Crigler-Najjar syndrome type 1: Report of a world registry. Hepatology 1996; 24: 311-5.
50. Schmid R, Axelrod J, Hammaker L, Swarm RL. Congenital jaundice in rats, due to a defect in glucuronide formation. J Clin Invest 1958; 37: 1123-30.
51. Blanckaert N, Heirwegh KP, Zaman Z. Comparison of the biliary excretion of the four isomers of bilirubin-IX in Wistar and homozygous Gunn rats. Biochem J 1977; 164: 229-36.
52. Muraca M, Fevery J. Influence of sex and sex steroids on bilirubin uridine diphosphate-glucuronosyltransferase activity of rat liver. Gastroenterology 1984; 87: 308-13.
53. Black M, Fevery J, Parker D, Jacobson J, Billing BH, Carson ER. Effect of phenobarbitone on plasma (14C)bilirubin clearance in patients with unconjugated hyperbilirubinaemia. Clin Sci Mol Med 1974; 46: 1-17.
54. Lankisch TO, Moebius U, Wehmeier M, et al. Gilbert's disease and atazanavir: From phenotype to UDP-glucuronosyltransferase haplotype. Hepatology 2006; 44: 1324-32.
55. Van Steenbergen W, Fevery J, De Groote J. Thyroid hormones and the hepatic handling of bilirubin. II. Effects of hypothyroidism and hyperthyroidism on the apparent maximal biliary secretion of bilirubin in the Wistar rat. J Hepatol 1988; 7: 229-38.
56. Van Steenbergen W, Fevery J. Effects of uridine diphosphate glucuronosyltransferase activity on the maximal secretion rate of bilirubin conjugates in the rat. Gastroenterology 1990; 99: 488-99.
57. Berk PD, Martin JF, Blaschke TF, Scharschmidt BF, Plotz PH. Unconjugated hyperbilirubinemia. Physiologic evaluation and experimental approaches to therapy. Ann Intern Med 1975; 82: 552-70.
58. Oshio C, Phillips MJ. Contractility of bile canaliculi: Implications for liver function. Science 1981; 212: 1041-2.
59. Phillips MJ, Oshio C, Miyairi M, Watanabe S, Smith CR. What is actin doing in the liver cell? Hepatology 1983; 3: 433-6.
60. Dumont M, D'Hont C, Lamri Y, et al. Effects of phalloidin and colchicine on diethylmaleate-induced choleresis and ultrastructural appearance of rat hepatocytes. Liver 1994; 14: 308-13.
61. Pauli-Magnus C, Stieger B, Meier Y, Kullak-Ublick GA, Meier PJ. Enterohepatic transport of bile salts and genetics of cholestasis. J Hepatol 2005; 43: 342-57.
62. Pauli-Magnus C, Meier PJ. Hepatobiliary transporters and drug-induced cholestasis. Hepatology 2006; 44: 778-87.
63. Geier A, Wagner M, Dietrich CG, Trauner M. Principles of hepatic organic anion transporter regulation during cholestasis, inflammation and liver regeneration. Biochim Biophys Acta 2007; 1773: 283-308.
64. Kaplan MM, Righetti A. Induction of rat liver alkaline phosphatase: The mechanism of the serum elevation in bile duct obstruction. J Clin Invest 1970; 49: 508-16.
65. Blanckaert N, Compernolle F, Leroy P, Van Houtte R, Fevery J, Heirwegh KP. The fate of bilirubin-IXalpha glucuronide in cholestasis and during storage in vitro. Intramolecular rearrangement to positional isomers of glucuronic acid. Biochem J 1978; 171: 203-14.
66. Van Hootegem P, Fevery J, Blanckaert N. Serum bilirubins in hepatobiliary disease: Comparison with other liver function tests and changes in the postobstructive period. Hepatology 1985; 5: 112-7.
67. Billing BH. Intestinal and enal metabolism of bilirubin, including enterohepatic circulation. In: Donald Ostrow J, ed. Bile Pigments and Jaundice. New York: Marcel Dekker Inc., 1986; 255-70.
68. Fevery J, Heirwegh K, De Groote J. Renal bilirubin clearance in liver patients. Clin Chim Acta 1967; 17: 63-71.
69. Elias MM, Mottino AD, Ochoa EJ. Transepithelial fate of bilirubin in the isolated rat kidney. Biochim Biophys Acta 1997; 1336: 7-14.
70. Fulop M, Katz S, Lawrence C. Extreme hyperbilirubinemia. Arch Intern Med 1971; 127: 254-8.
71. Medley MM, Hooker RL, Rabinowitz S, Holton R, Jaffe BM. Correction of congenital indirect hyperbilirubinemia by small intestinal transplantation. Am J Surg 1995; 169: 20-7.
72. Foliot A, Christoforov B, Petite JP, Etienne JP, Housset E, Dubois M. Bilirubin UDP-glucuronyltransferase activity of Wistar rat kidney. Am J Physiol 1975; 229: 340-3.
73. Vitek L, Majer F, Muchova L, et al. Identification of bilirubin reduction products formed by Clostridium perfringens isolated from human neonatal fecal flora. J Chromatogr 2006; B833: 149-57.
74. Vitek L, Kotal P, Jirsa M, et al. Intestinal colonization leading to fecal urobilinoid excretion may play a role in the pathogenesis of neonatal jaundice. J Pediatr Gastroenterol Nutr 2000; 30: 294-8.
75. Brink MA, Slors JF, Keulemans YC, et al. Enterohepatic cycling of bilirubin: A putative mechanism for pigment gallstone formation in ileal Crohn's disease. Gastroenterology 1999; 116: 1420-7.
76. Werner M, Tolls RE, Hultin JV, Mellecker J. Influence of sex and age on the normal range of eleven serum constituents. Z Klin Chem Klin Biochem 1970; 8: 105-1.
77. Owens D, Evans J. Population studies on Gilbert's syndrome. J Med Genet 1975; 12: 152-6.
78. Muraca M, Blanckaert N. Liquid-chromatographic assay and identification of mono- and diester conjugates of bilirubin in normal serum. Clin Chem 1983; 29: 1767-71.
79. Zucker SD, Horn PS, Sherman KE. Serum bilirubin levels in the U.S. population: Gender effect and inverse correlation with colorectal cancer. Hepatology 2004; 40: 827-35.
80. Muraca M, Fevery J, Blanckaert N. Relationships between serum bilirubins and production and conjugation of bilirubin. Gastroenterology 1987; 92: 309-17.
81. Fevery J, Blanckaert N, Leroy P, Michiels R, Heirwegh KP. Analysis of bilirubins in biological fluids by extraction and thin-layer chromatography of the intact tetrapyrroles: Application to bile of patients with Gilbert's syndrome, hemolysis, or cholelithiasis. Hepatology 1983; 3: 177-83.
82. LaMont JT, Isselbacher KJ. Postoperative jaundice. N Engl J Med 1973; 288: 305-7.
83. Owen JS, Brown DJ, Harry DS, et al. Erythrocyte echinocytosis in liver disease. Role of abnormal plasma high density lipoproteins. J Clin Invest 1985; 76: 2275-85.
84. Fong TL, McHutchison JG, Reynolds TB. Hyperthyroidism and hepatic dysfunction. A case series analysis. J Clin Gastroenterol 1992; 14: 240-4.
85. McIntyre N, Collins P. The liver in cardiovascular and pulmonary disease. ChaEter 24.1. In: Bircher J, et al: ed. Oxford Textbook of Clinical Hepatology. Oxford: Oxford University Press, 1999; 1671-983.
86. Dichtl W, Vogel W, Dunst KM, et al. Cardiac hepatopathy before and after heart transplantation. Transpl Int 2005; 18: 697-702.
87. Davis DR, Yeary RA. Effects of sulfadimethoxine on tissue distribution of (14C)bilirubin in the newborn and adult hyperbilirubinemic Gunn rat. Pediatr Res 1975; 9: 846-50.
88. Wennberg RP, Ahlfors CE, Bhutani VK, Johnson LH, Shapiro SM. Toward understanding kernicterus: A challenge to improve the management of jaundiced newborns. Pediatrics 2006; 117: 474-85.
89. Peters WHM, te Morsche RHM, Roelofs HMJ. Combined polymorphisms in UDP-glucuronosyltransferases 1A1 and 1A6: Implications for patients with Gilbert's syndrome. J Hepatol 2003; 38: 3-8.
90. Martin JF, Vierling JM, Wolkoff AW, et al. Abnormal hepatic transport of indocyanine green in Gilbert's syndrome. Gastroenterology 1976; 70: 385-91.
91. Stocker R, Glazer AN, Ames BN. Antioxidant activity of albumin-bound bilirubin. Proc Natl Acad Sci USA 1987; 84: 5918-22.
92. Novotny L, Vitek L. Inverse relationship between serum bilirubin and atherosclerosis in men: A meta-analysis of published studies. Exp Biol Med 2003; 228: 568-71.
93. Lin JP, O'Donnell CJ, Schwaiger JP, et al. Association between the UGT1A1 * 28 allele, bilirubin levels, and coronary heart disease in the Framingham Heart Study. Circulation 2006; 114: 1476-81.
94. Temme EH, Zhang J, Schouten EG, Kesteloot H. Serum bilirubin and 10-year mortality risk in a Belgian population. Cancer Causes Control 2001; 12: 887-94.
95. Jinno H, Tanaka-Kagawa T, Hanioka N, et al. Glucuronidation of 7-ethyl-10-hydroxycamptothecin (SN-38), an active metabolite of irinotecan (CPT-11), by human UGT1A1 variants, G71R, P229Q, and Y486D. Drug Metab Dispos 2003; 31: 108-13.
96. Innocenti F, Undevia SD, Iyer L, et al. Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. J Clin Oncol 2004; 22: 1382-8.
97. Zucker SD, Qin X, Rouster SD, et al. Mechanism of indinavir-induced hyperbilirubinemia. Proc Natl Acad Sci 2001; 98: 12671-6.
98. Rotger M, Taffe P, Swiss HIV Cohort Study, et al. Gilbert syndrome and the development of antiretroviral therapy-associated hyperbilirubinemia. J Infect Dis 2005; 192: 1381-6.
99. Whitmer DI, Gollan JL. Mechanisms and significance of fasting and dietary hyperbilirubinemia. Semin Liver Dis 1983; 3: 42-51.
100. Bakken AF, Thaler MM, Schmid R. Metabolic regulation of heme catabolism and bilirubin production. I. Hormonal control of hepatic heme oxygenase activity. J Clin Invest 1972; 51: 530-6.
101. Lundh B, Johansson MB, Mercke C, Cavallin-Stahl E. Enhancement of heme catabolism by caloric restriction in man. Scand J Clin Lab Invest 1972; 30: 421-7.
102. Kotal P, Vitek L, Fevery J. Fasting-related hyperbilirubinemia in rats: the effect of decreased intestinal motility. Gastroenterology 1996; 111: 217-23.
103. Fevery J. Fasting hyperbilirubinemia: Unraveling the mechanism involved. Gastroenterology 1997; 113: 1798-800.
104. Au WY, Cheung WC, Tung H. Gilbert's syndrome complicating long term parenteral nutrition. J Hepatol 2004; 41: 168-9.
105. Fevery J, Heirwegh KP, De Groote J. Unconjugated hyperbilirubinaemia in achalasia. Gut 1974; 15: 121-4.
106. Trioche P, Chalas J, Francoual J, et al. Jaundice with hypertrophic pyloric stenosis as an early manifestation of Gilbert syndrome. Arch Dis Child 1999; 81: 301-3.