Bilirubin, Impaired Conjugation Treatment & Management

  • Author: Sandeep Mukherjee, MB, BCh, MPH, FRCPC; Chief Editor: Julian Katz, MD   more...
 
Updated: Jan 3, 2010
 

Medical Care

  • Crigler-Najjar type I syndrome: The therapeutic goal is to produce a sustained reduction in plasma bilirubin concentration. Many different therapies have been tried in experimental protocols. No medical therapy has been found to be effective in patients with Crigler-Najjar type I syndrome; therefore, the treatment of choice for Crigler-Najjar type I syndrome is liver transplantation. Performance of liver transplantation should occur prior to the onset of kernicterus.
    • Medical therapies consist of phototherapy, plasmapheresis, calcium phosphate supplementation, calcium phosphate, and orlistat.
    • Hepatocyte transplantation is being studied as an alternative to liver transplantation, and partial success has been reported in one patient.[9]
    • Introduction of a normal bilirubin-UGT gene (UGT1A1) has the potential for curing the genetic defect leading to Crigler-Najjar syndrome. Although animal studies have resulted in long-term correction of serum bilirubin levels, none of these studies have translated into clinical trials.[10, 11]
  • Crigler-Najjar type II syndrome: Phenobarbital therapy has been shown to be effective in reducing plasma bilirubin levels in patients with Crigler-Najjar type II syndrome. This can be accomplished by the administration of phenobarbital (60-180 mg/d in divided doses), which reduces serum bilirubin levels by at least 25%. A response should be expected within 2-3 weeks. A similar benefit can be observed with clofibrate, which is associated with fewer adverse effects. However, patients often do well, even in the absence of therapy.
  • Gilbert syndrome: No therapy is necessary; however, many therapeutic approaches have been used. As with Crigler-Najjar type II syndrome, phenobarbital has been shown to decrease bilirubin production. The prognosis is excellent. The most important aspect in the care of these patients is recognition of the disorder and its inconsequential nature.
  • Physiologic jaundice: No treatment is needed.
  • Breast milk jaundice and other pathologic causes of jaundice in the neonate: Phototherapy can be used.
    • Phototherapy consists of exposing the infant's skin to light. It is a safe and efficient method to reduce the toxicity of bilirubin and to increase its elimination. The use of phototherapy decreases the risk that the total serum bilirubin concentration will reach the level at which exchange transfusion is recommended.
    • Phototherapy converts bilirubin into lumirubin in a process of structural isomerization that is not reversible. Lumirubin is a more soluble substance than bilirubin and is excreted without conjugation into bile and urine.
    • Maintaining adequate hydration and urine output is important during phototherapy to prevent dehydration.
    • An uncommon complication of phototherapy is the so-called bronze baby syndrome. This occurs in some infants with cholestatic jaundice and is manifested by a dark, grayish brown discoloration of the skin, serum, and urine. The condition gradually resolves without sequelae within several weeks after discontinuation of therapy.
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Surgical Care

Liver transplantation has been performed for the treatment of Crigler-Najjar type I syndrome.

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Contributor Information and Disclosures
Author

Sandeep Mukherjee, MB, BCh, MPH, FRCPC  Associate Professor, Department of Internal Medicine, Section of Gastroenterology and Hepatology, University of Nebraska Medical Center; Consulting Staff, Section of Gastroenterology and Hepatology, Veteran Affairs Medical Center

Sandeep Mukherjee, MB, BCh, MPH, FRCPC is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Coauthor(s)

Jeanette G Smith, MD  Fellow, Department of Gastroenterology-Hepatology, University of Connecticut School of Medicine

Jeanette G Smith, MD is a member of the following medical societies: American College of Physicians, American Gastroenterological Association, and American Public Health Association

Disclosure: Nothing to disclose.

Annie T Chemmanur, MD  Attending Physician, Metrowest Medical Center and University of Massachusetts Memorial Hospital, Marlborough Campus

Annie T Chemmanur, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American Gastroenterological Association, American Medical Association, and Massachusetts Medical Society

Disclosure: Nothing to disclose.

George Y Wu, MD, PhD  Professor, Department of Medicine, Director, Hepatology Section, Herman Lopata Chair in Hepatitis Research, University of Connecticut School of Medicine

George Y Wu, MD, PhD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, American Medical Association, American Society for Clinical Investigation, and Association of American Physicians

Disclosure: Humana Press Consulting fee Consulting; Novartis Consulting fee Review panel membership

Shirley Donelson, MD  Program Director, Assistant Professor, Department of Internal Medicine, Division of Digestive Diseases, University of Mississippi Medical School

Shirley Donelson, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Medical Association, and Mississippi State Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

David Eric Bernstein, MD  Chief, Section of Hepatology, North Shore University Hospital, Director, Associate Professor, Department of Internal Medicine, Division of Hepatology, New York University School of Medicine

David Eric Bernstein, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

James L Achord, MD  Professor Emeritus, Department of Medicine, Division of Digestive Diseases, University of Mississippi School of Medicine

James L Achord, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Medical Association, American Society for Gastrointestinal Endoscopy, Mississippi State Medical Association, New York Academy of Sciences, Sigma Xi, and Southern Medical Association

Disclosure: Nothing to disclose.

Alex J Mechaber, MD, FACP  Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine

Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine

Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD  Clinical Professor of Medicine, Drexel University College of Medicine; Consulting Staff, Department of Medicine, Section of Gastroenterology and Hepatology, Hospital of the Medical College of Pennsylvania

Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law Medicine and Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility

Disclosure: Nothing to disclose.

References

  1. McGrath M, Lepine J, Lee IM, et al. Genetic variations in UGT1A1 and UGT2B7 and endometrial cancer risk. Pharmacogenet Genomics. Mar 2009;19(3):239-43. [Medline].

  2. Saeki M, Saito Y, Sai K, et al. A combinatorial haplotype of the UDP-glucuronosyltransferase 1A1 gene (#60-#IB) increases total bilirubin concentrations in Japanese volunteers. Clin Chem. Feb 2007;53(2):356-8. [Medline].

  3. Saito A, Kawamoto M, Kamatani N. Association study between single-nucleotide polymorphisms in 199 drug-related genes and commonly measured quantitative traits of 752 healthy Japanese subjects. J Hum Genet. Jun 2009;54(6):317-23. [Medline].

  4. Zhou YY, Lee LY, Ng SY, et al. UGT1A1 haplotype mutation among Asians in Singapore. Neonatology. 2009;96(3):150-5. [Medline].

  5. Strassburg CP. Pharmacogenetics of Gilbert's syndrome. Pharmacogenomics. Jun 2008;9(6):703-15. [Medline].

  6. Lankisch TO, Behrens G, Ehmer U, et al. Gilbert's syndrome and hyperbilirubinemia in protease inhibitor therapy--an extended haplotype of genetic variants increases risk in indinavir treatment. J Hepatol. May 2009;50(5):1010-8. [Medline].

  7. Kweekel D, Guchelaar HJ, Gelderblom H. Clinical and pharmacogenetic factors associated with irinotecan toxicity. Cancer Treat Rev. Nov 2008;34(7):656-69. [Medline].

  8. Cakmak A, Calik M, Atas A, Hirfanoglu I, Erel O. Can haptoglobin be an indicator for the early diagnosis of neonatal jaundice?. J Clin Lab Anal. 2008;22(6):409-14. [Medline].

  9. Fox IJ, Chowdhury JR, Kaufman SS, et al. Treatment of the Crigler-Najjar syndrome type I with hepatocyte transplantation. N Engl J Med. May 14 1998;338(20):1422-6. [Medline].

  10. Miranda PS, Bosma PJ. Towards liver-directed gene therapy for Crigler-Najjar syndrome. Curr Gene Ther. Apr 2009;9(2):72-82. [Medline].

  11. Birraux J, Menzel O, Wildhaber B, et al. A step toward liver gene therapy: efficient correction of the genetic defect of hepatocytes isolated from a patient with Crigler-Najjar syndrome type 1 with lentiviral vectors. Transplantation. Apr 15 2009;87(7):1006-12. [Medline].

  12. 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. Oct 3 2006;114(14):1476-81. [Medline].

  13. Lin JP, Schwaiger JP, Cupples LA, O'Donnell CJ, et al. Conditional linkage and genome-wide association studies identify UGT1A1 as a major gene for anti-atherogenic serum bilirubin levels--the Framingham Heart Study. Atherosclerosis. Sep 2009;206(1):228-33. [Medline].

  14. Vitek L, Schwertner HA. Protective effects of serum bilirubin on peripheral vascular disease. Ann Hepatol. Jan-Mar 2008;7(1):94-5. [Medline].

  15. Schwertner HA, Vítek L. Gilbert syndrome, UGT1A1*28 allele, and cardiovascular disease risk: possible protective effects and therapeutic applications of bilirubin. Atherosclerosis. May 2008;198(1):1-11. [Medline].

  16. Aono S, Adachi Y, Uyama E. Analysis of genes for bilirubin UDP-glucuronosyltransferase in Gilbert's syndrome. Lancet. Apr 15 1995;345(8955):958-9. [Medline].

  17. Bosma PJ, Chowdhury JR, Bakker C. The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert's syndrome. N Engl J Med. Nov 2 1995;333(18):1171-5. [Medline].

  18. Chopra S. Disorders of the Liver. Philadelphia, Pa: Lea & Febiger; 1988:23-37.

  19. Chopra S, May RJ. Pathophysiology of Gastrointestinal Diseases. Little Brown & Company;1989: 312-317.

  20. Gabilan JC, Benattar C, Lindenbaum A. Clofibrate treatment of neonatal jaundice. Pediatrics. Oct 1990;86(4):647-8.

  21. Kadakol A, Ghosh SS, Sappal BS. Genetic lesions of bilirubin uridine-diphosphoglucuronate glucuronosyltransferase (UGT1A1) causing Crigler-Najjar and Gilbert syndromes: correlation of genotype to phenotype. Hum Mutat. Oct 2000;16(4):297-306.

  22. Schiff ER, Sorrell MF and Maddrey WC, editors. Schiff's Diseases of the Liver. 8th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 1999:151-74.

  23. Seppen J, Bosma PJ, Goldhoorn BG. Discrimination between Crigler-Najjar type I and II by expression of mutant bilirubin uridine diphosphate-glucuronosyltransferase. J Clin Invest. Dec 1994;94(6):2385-91.

  24. Tada K, Roy-Chowdhury N, Prasad V. Long-term amelioration of bilirubin glucuronidation defect in Gunn rats by transplanting genetically modified immortalized autologous hepatocytes. Cell Transplant. Nov-Dec 1998;7(6):607-16.

  25. Vroemen JP, Blanckaert N, Buurman WA. Treatment of enzyme deficiency by hepatocyte transplantation in rats. J Surg Res. Sep 1985;39(3):267-75.

 
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