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Unconjugated Hyperbilirubinemia Differential Diagnoses

  • Author: Hisham Nazer, MB, BCh, FRCP, , DTM&H; Chief Editor: BS Anand, MD  more...
 
Updated: May 02, 2016
 
 

Diagnostic ConsiderationsIneffective erythropoiesis (ELB production)Other conditions

The American Academy of Pediatrics established guidelines for the diagnosis and treatment of hyperbilirubinemia in newborns in 2004.[57] These are available through the American Academy of Pediatrics.

A marked increase in early-labeled bilirubing (ELB) formation has been documented in diseases associated with ineffective erythropoiesis, including the following:

  • Iron deficiency anemia
  • Pernicious anemia
  • Thalassemia
  • Erythropoietic porphyria
  • Lead poisoning

Although no specific test exists for physiologic jaundice, other causes of jaundice should be considered in infants with one or more of the following:

  • Jaundice occurring within 24 hours of birth
  • Serum concentrations of unconjugated bilirubin of 11-12 mg/dL in infants who are formula-fed or 14-15 mg/dL in infants who are breastfed
  • Increased levels of conjugated bilirubin (>2 mg/dL)
  • Jaundice persisting for more than 2 weeks

Gilbert syndrome

Gilbert syndrome has a broad differential diagnosis because numerous causes of unconjugated hyperbilirubinemia must be considered. In particular, the possibility of biliary disease must be taken into account.

Other conditions to be considered include the following:

  • Physiologic neonatal jaundice
  • Hemolysis
  • Hematoma
  • Acute and chronic liver disease
  • Primary hyperbilirubinemia from ineffective erythropoiesis
  • Infections
  • Cardiac disease - Eg, congestive heart failure or prosthetic heart valves
  • Rhabdomyolysis
  • High-altitude living
  • Medications - Eg, probenecid, rifampicin, or other antibiotics
  • Thyrotoxicosis

Additional considerations in the diagnosis of impaired bilirubin conjugation include the following:

  • Dyserythropoiesis
  • Portosystemic shunts
  • Neonates
  • Hyperthyroidism
  • Ethinyl estradiol

Differential Diagnoses

 
 
Contributor Information and Disclosures
Author

Hisham Nazer, MB, BCh, FRCP, , DTM&H Professor of Pediatrics, Consultant in Pediatric Gastroenterology, Hepatology and Clinical Nutrition, University of Jordan Faculty of Medicine, Jordan

Hisham Nazer, MB, BCh, FRCP, , DTM&H is a member of the following medical societies: American Association for Physician Leadership, Royal College of Paediatrics and Child Health, Royal College of Surgeons in Ireland, Royal Society of Tropical Medicine and Hygiene, Royal College of Physicians and Surgeons of the United Kingdom

Disclosure: Nothing to disclose.

Coauthor(s)

Praveen K Roy, MD, AGAF Chief of Gastroenterology, Presbyterian Hospital; Medical Director of Endoscopy, Presbyterian Medical Group; Adjunct Associate Research Scientist, Lovelace Respiratory Research Institute

Praveen K Roy, MD, AGAF is a member of the following medical societies: American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Additional Contributors

Ann Ouyang, MBBS Professor, Department of Internal Medicine, Pennsylvania State University College of Medicine; Attending Physician, Division of Gastroenterology and Hepatology, Milton S Hershey Medical Center

Disclosure: Nothing to disclose.

Julian Katz, MD Clinical Professor of Medicine, Drexel University College of Medicine

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 & Ethics, American Trauma Society, Association of American Medical Colleges, Physicians for Social Responsibility

Disclosure: Nothing to disclose.

Acknowledgements

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

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

Disclosure: Nothing to disclose.

Showkat Bashir, MD Assistant Professor, Department of Medicine, Division of Gastroenterology, George Washington University, Washington, DC

Showkat Bashir, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, and American Medical Association

Disclosure: Nothing to disclose.

David Eric Bernstein, MD Director of Hepatology, North Shore University Hospital; Professor of Clinical Medicine, Albert Einstein College 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.

Manoop S Bhutani, MD Professor, Co-Director, Center for Endoscopic Research, Training and Innovation (CERTAIN), Director, Center for Endoscopic Ultrasound, Department of Medicine, Division of Gastroenterology, University of Texas Medical Branch; Director, Endoscopic Research and Development, The University of Texas MD Anderson Cancer Center

Manoop S Bhutani, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Institute of Ultrasound in Medicine, and American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Jack Bragg, DO Associate Professor, Department of Clinical Medicine, University of Missouri School of Medicine

Jack Bragg, DO is a member of the following medical societies: American College of Osteopathic Internists and American Osteopathic 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.

Carmen Cuffari, MD Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine

Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, and Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Gautam Dehadrai, MD Department Chair, Section Chief, Department of Interventional Radiology, Norman Regional Hospital

Gautam Dehadrai, MD is a member of the following medical societies: American College of Radiology, Medical Council of India, and Radiological Society of North America

Disclosure: Nothing to disclose.

Jayant Deodhar, MD Associate Professor in Pediatrics, BJ Medical College, India; Honorary Consultant, Departments of Pediatrics and Neonatology, King Edward Memorial Hospital, India

Disclosure: Nothing to disclose.

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.

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

Disclosure: Merck Honoraria Speaking and teaching; Ikaria Pharmaceuticals Honoraria Board membership

Dena Nazer, MD Medical Director, Child Protection Center, Children's Hospital of Michigan; Assistant Professor, Wayne State University

Dena Nazer, MD is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, American Professional Society on the Abuse of Children, and Helfer Society

Disclosure: Nothing to disclose.

Mohamed Othman, MD Resident Physician, Department of Internal Medicine, University of New Mexico School of Medicine

Disclosure: Nothing to disclose.

Nuri Ozden, MD Assistant Professor, Department of Internal Medicine, Meharry Medical College

Nuri Ozden, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Tushar Patel, MB, ChB Professor of Medicine, Ohio State University Medical Center

Tushar Patel, MB, ChB is a member of the following medical societies: American Association for the Study of Liver Diseases and American Gastroenterological Association

Disclosure: Nothing to disclose.

David A Piccoli, MD Chief of Pediatric Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia; Professor, University of Pennsylvania School of Medicine

David A Piccoli, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, and North American Society for Pediatric Gastroenterology and Nutrition

Disclosure: Nothing to disclose.

Alessio Pigazzi, MD PhD, Head, Minimally Invasive Surgery Program, Division of Surgery, Department of General Oncologic Surgery, City of Hope National Medical Center

Disclosure: Nothing to disclose.

Praveen K Roy, MD, AGAF Gastroenterologist, Ochsner Clinic Foundation; Adjunct Associate Research Scientist, Lovelace Respiratory Research Institute; Editor-in-Chief, The Internet Journal of Gasteroenterology; Editorial Board, Signal Transduction Insights; Editorial Board, The Internet Journal of Epidemiology; Editorial Board, Gastrointestinal Endoscopy Review Letter

Praveen K Roy, MD, AGAF is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, and American Society of Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

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.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

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: Springer Consulting fee Consulting; Gilead Consulting fee Review panel membership; Vertex Honoraria Speaking and teaching; Bristol-Myers Squibb Honoraria Speaking and teaching; Springer Royalty Review panel membership; Merck Honoraria Speaking and teaching

References
  1. Memon N, Weinberger BI, Hegyi T, Aleksunes LM. Inherited disorders of bilirubin clearance. Pediatr Res. 2015 Nov 23. [Medline].

  2. Dani C, Pratesi S, Raimondi F, Romagnoli C, for the Task Force for Hyperbilirubinemia of the Italian Society of Neonatology. Italian guidelines for the management and treatment of neonatal cholestasis. Ital J Pediatr. 2015 Oct 1. 41:69. [Medline].

  3. Hafkamp AM, Nelisse-Haak R, Sinaasappel M, Oude Elferink RP, Verkade HJ. Orlistat treatment of unconjugated hyperbilirubinemia in Crigler-Najjar disease: a randomized controlled trial. Pediatr Res. 2007 Dec. 62(6):725-30. [Medline].

  4. Sisson TR, Drummond GS, Samonte D, Calabio R, Kappas A. Sn-protoporphyrin blocks the increase in serum bilirubin levels that develops postnatally in homozygous Gunn rats. J Exp Med. 1988 Mar 1. 167(3):1247-52. [Medline]. [Full Text].

  5. Smith JR, Donze A, Schuller L. An evidence-based review of hyperbilirubinemia in the late preterm infant, with implications for practice: management, follow-up, and breastfeeding support. Neonatal Netw. 2007 Nov-Dec. 26(6):395-405. [Medline].

  6. Lucey JF, Suresh GK, Kappas A. Crigler-Najjar syndrome, 1952-2000: learning from parents and patients about a very rare disease and using the internet to recruit patients for studies. Pediatrics. 2000 May. 105(5):1152-3. [Medline].

  7. Falcão AS, Silva RF, Fernandes A, Brito MA, Brites D. Influence of hypoxia and ischemia preconditioning on bilirubin damage to astrocytes. Brain Res. 2007 May 29. 1149:191-9. [Medline].

  8. Nydegger A, Bednarz A, Hardikar W. Use of daytime phototherapy for Crigler-Najjar disease. J Paediatr Child Health. 2005 Jul. 41(7):387-9. [Medline].

  9. Morioka D, Kasahara M, Takada Y, Corrales JP, Yoshizawa A, Sakamoto S, et al. Living donor liver transplantation for pediatric patients with inheritable metabolic disorders. Am J Transplant. 2005 Nov. 5(11):2754-63. [Medline].

  10. Bosma PJ, Chowdhury NR, Goldhoorn BG, Hofker MH, Oude Elferink RP, Jansen PL, 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 May. 15(5):941-7. [Medline].

  11. Toietta G, Mane VP, Norona WS, Finegold MJ, Ng P, McDonagh AF, et al. Lifelong elimination of hyperbilirubinemia in the Gunn rat with a single injection of helper-dependent adenoviral vector. Proc Natl Acad Sci U S A. 2005 Mar 15. 102(11):3930-5. [Medline]. [Full Text].

  12. Fretzayas A, Moustaki M, Liapi O, Karpathios T. Gilbert syndrome. Eur J Pediatr. 2012 Jan. 171(1):11-5. [Medline].

  13. Lopardo G, Bissio E, Espinola L, Gallego P, Stambullian M, Gadano A. Short communication: fasting increases serum concentrations of bilirubin in patients receiving atazanavir: results from a pilot study. AIDS Res Hum Retroviruses. 2013 Mar. 29(3):456-60. [Medline]. [Full Text].

  14. Chang PF, Lin YC, Liu K, Yeh SJ, Ni YH. Prolonged unconjugated hyperbiliriubinemia in breast-fed male infants with a mutation of uridine diphosphate-glucuronosyl transferase. J Pediatr. 2009 Dec. 155(6):860-3. [Medline].

  15. D'Silva S, Colah RB, Ghosh K, Mukherjee MB. Combined effects of the UGT1A1 and OATP2 gene polymorphisms as major risk factor for unconjugated hyperbilirubinemia in Indian neonates. Gene. 2014 Aug 15. 547(1):18-22. [Medline].

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

  17. Zhou YY, Lee LY, Ng SY, Hia CP, Low KT, Chong YS, et al. UGT1A1 haplotype mutation among Asians in Singapore. Neonatology. 2009. 96(3):150-5. [Medline].

  18. 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. 2009 Jun. 54(6):317-23. [Medline].

  19. Servedio V, d'Apolito M, Maiorano N, Minuti B, Torricelli F, Ronchi F, et al. Spectrum of UGT1A1 mutations in Crigler-Najjar (CN) syndrome patients: identification of twelve novel alleles and genotype-phenotype correlation. Hum Mutat. 2005 Mar. 25(3):325. [Medline].

  20. Jansen PL. Diagnosis and management of Crigler-Najjar syndrome. Eur J Pediatr. 1999 Dec. 158 Suppl 2:S89-94. [Medline].

  21. Stevenson DK, Vreman HJ, Wong RJ. Bilirubin production and the risk of bilirubin neurotoxicity. Semin Perinatol. 2011 Jun. 35(3):121-6. [Medline].

  22. Liu WL, Li F, He ZX, Jiang HY, Ai R, Chen XX, et al. Analysis of bilirubin UDP-glucuronosyltransferase gene mutations in an unusual Crigler-Najjar syndrome patient. Mol Med Rep. 2012 Sep. 6(3):667-9. [Medline].

  23. 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 Mar-Apr. 38(2):78-82. [Medline].

  24. Papez MJ, Civalier CJ, Thorne LB, Gulley ML. UGT1A1 promoter genotype is not strongly associated with severity of coronary artery disease. Diagn Mol Pathol. 2009 Dec. 18(4):226-31. [Medline].

  25. Tapan S, Dogru T, Tasci I, Ercin CN, Ozgurtas T, Erbil MK. Soluble CD40 ligand and soluble P-selectin levels in Gilbert's syndrome: a link to protection against atherosclerosis?. Clin Biochem. 2009 Jun. 42(9):791-5. [Medline].

  26. Ferraris A, D'Amato G, Nobili V, Torres B, Marcellini M, Dallapiccola B. Combined test for UGT1A1 -3279T-->G and A(TA)nTAA polymorphisms best predicts Gilbert's syndrome in Italian pediatric patients. Genet Test. 2006 Summer. 10(2):121-5. [Medline].

  27. Hsieh TY, Shiu TY, Huang SM, Lin HH, Lee TC, Chen PJ, et al. Molecular pathogenesis of Gilbert's syndrome: decreased TATA-binding protein binding affinity of UGT1A1 gene promoter. Pharmacogenet Genomics. 2007 Apr. 17(4):229-36. [Medline].

  28. Petit FM, Hébert M, Gajdos V, Mollet-Boudjemline A, Labrune P. Comments on seven novel mutations of the UGT1A1 gene in patients with unconjugated hyperbilirubinemia by D'Apolito et al. Haematologica. 2007 Jul. 92(7):e80. [Medline].

  29. Rigato I, Cravatari M, Avellini C, Ponte E, Crocè SL, Tiribelli C. Drug-induced acute cholestatic liver damage in a patient with mutation of UGT1A1. Nat Clin Pract Gastroenterol Hepatol. 2007 Jul. 4(7):403-8. [Medline].

  30. Teng HC, Huang MJ, Tang KS, Yang SS, Tseng CS, Huang CS. Combined UGT1A1 and UGT1A7 variant alleles are associated with increased risk of Gilbert's syndrome in Taiwanese adults. Clin Genet. 2007 Oct. 72(4):321-8. [Medline].

  31. Ehmer U, Lankisch TO, Erichsen TJ, Kalthoff S, Freiberg N, Wehmeier M, et al. Rapid allelic discrimination by TaqMan PCR for the detection of the Gilbert's syndrome marker UGT1A1*28. J Mol Diagn. 2008 Nov. 10(6):549-52. [Medline]. [Full Text].

  32. Sneitz N, Bakker CT, de Knegt RJ, Halley DJ, Finel M, Bosma PJ. Crigler-Najjar syndrome in The Netherlands: identification of four novel UGT1A1 alleles, genotype-phenotype correlation, and functional analysis of 10 missense mutants. Hum Mutat. 2010 Jan. 31(1):52-9. [Medline].

  33. Canu G, Minucci A, Zuppi C, Capoluongo E. Gilbert and Crigler Najjar syndromes: An update of the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene mutation database. Blood Cells Mol Dis. 2013 Apr. 50(4):273-80. [Medline].

  34. Fang JL, Lazarus P. Correlation between the UDP-glucuronosyltransferase (UGT1A1) TATAA box polymorphism and carcinogen detoxification phenotype: significantly decreased glucuronidating activity against benzo(a)pyrene-7,8-dihydrodiol(-) in liver microsomes from subjects with the UGT1A1*28 variant. Cancer Epidemiol Biomarkers Prev. 2004 Jan. 13(1):102-9. [Medline].

  35. Farheen S, Sengupta S, Santra A, Pal S, Dhali GK, Chakravorty M, et al. Gilbert's syndrome: High frequency of the (TA)7 TAA allele in India and its interaction with a novel CAT insertion in promoter of the gene for bilirubin UDP-glucuronosyltransferase 1 gene. World J Gastroenterol. 2006 Apr 14. 12(14):2269-75. [Medline].

  36. Jirsa M, Petrasek J, Vitek L. Linkage between A(TA)7TAA and -3279T>G mutations in UGT1A1 is not essential for pathogenesis of Gilbert syndrome. Liver Int. 2006 Dec. 26(10):1302-3. [Medline].

  37. Maruo Y, D'Addario C, Mori A, Iwai M, Takahashi H, Sato H, et al. Two linked polymorphic mutations (A(TA)7TAA and T-3279G) of UGT1A1 as the principal cause of Gilbert syndrome. Hum Genet. 2004 Nov. 115(6):525-6. [Medline].

  38. Tzetis M, Kanavakis E, Tsezou A, Ladis V, Pateraki E, Georgakopoulou T, et al. Gilbert syndrome associated with beta-thalassemia. Pediatr Hematol Oncol. 2001 Dec. 18(8):477-84. [Medline].

  39. Seo YS, Keum B, Park S, Kim du R, Kwon YD, Kim YS, et al. Gilbert's syndrome phenotypically expressed as Crigler-Najjar syndrome type II. Scand J Gastroenterol. 2007 Apr. 42(4):540-1. [Medline].

  40. Udomuksorn W, Elliot DJ, Lewis BC, Mackenzie PI, Yoovathaworn K, Miners JO. Influence of mutations associated with Gilbert and Crigler-Najjar type II syndromes on the glucuronidation kinetics of bilirubin and other UDP-glucuronosyltransferase 1A substrates. Pharmacogenet Genomics. 2007 Dec. 17(12):1017-29. [Medline].

  41. Huang CS, Huang MJ, Lin MS, Yang SS, Teng HC, Tang KS. Genetic factors related to unconjugated hyperbilirubinemia amongst adults. Pharmacogenet Genomics. 2005 Jan. 15(1):43-50. [Medline].

  42. Origa R, Galanello R, Perseu L, Tavazzi D, Domenica Cappellini M, Terenzani L, et al. Cholelithiasis in thalassemia major. Eur J Haematol. 2009 Jan. 82(1):22-5. [Medline].

  43. Tsezou A, Tzetis M, Giannatou E, Spanos I, Roma E, Fretzayas A, et al. Gilbert syndrome as a predisposing factor for cholelithiasis risk in the Greek adult population. Genet Test Mol Biomarkers. 2009 Feb. 13(1):143-6. [Medline].

  44. Clementi M, Di Gianantonio E, Fabris L, Forabosco P, Strazzabosco M, Tenconi R, et al. Inheritance of hyperbilirubinemia: evidence for a major autosomal recessive gene. Dig Liver Dis. 2007 Apr. 39(4):351-5. [Medline].

  45. Manning D, Todd P, Maxwell M, Jane Platt M. Prospective surveillance study of severe hyperbilirubinaemia in the newborn in the UK and Ireland. Arch Dis Child Fetal Neonatal Ed. 2007 Sep. 92(5):F342-6. [Medline]. [Full Text].

  46. Sagili H, Pramya N, Jayalaksmi D, Rani R. Crigler-Najjar syndrome II and pregnancy outcome. J Obstet Gynaecol. 2012 Feb. 32(2):188-9. [Medline].

  47. Kaneko J, Sugawara Y, Maruo Y, Sato H, Tamura S, Imamura H, et al. Liver transplantation using donors with Gilbert syndrome. Transplantation. 2006 Jul 27. 82(2):282-5. [Medline].

  48. Yilmaz M, Unal B, Isik B, Ozgor D, Piskin T, Ersan V, et al. Can an extended right lobe be harvested from a donor with Gilbert's syndrome for living-donor liver transplantation? Case report. Transplant Proc. 2012 Jul-Aug. 44(6):1640-3. [Medline].

  49. Lin JP, O'Donnell CJ, Schwaiger JP, Cupples LA, Lingenhel A, Hunt SC, et al. Association between the UGT1A1*28 allele, bilirubin levels, and coronary heart disease in the Framingham Heart Study. Circulation. 2006 Oct 3. 114(14):1476-81. [Medline].

  50. Lin JP, Schwaiger JP, Cupples LA, O'Donnell CJ, Zheng G, Schoenborn V, 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. 2009 Sep. 206(1):228-33. [Medline]. [Full Text].

  51. Maruhashi T, Soga J, Fujimura N, Idei N, Mikami S, Iwamoto Y, et al. Hyperbilirubinemia, augmentation of endothelial function, and decrease in oxidative stress in Gilbert syndrome. Circulation. 2012 Jul 31. 126(5):598-603. [Medline].

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

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

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

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

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

  57. American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2004 Jul. 114 (1):297-316. [Medline].

  58. 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].

  59. Esteban A, Pérez-Mateo M. Heterogeneity of paracetamol metabolism in Gilbert's syndrome. Eur J Drug Metab Pharmacokinet. 1999 Jan-Mar. 24(1):9-13. [Medline].

  60. Rauchschwalbe SK, Zühlsdorf MT, Wensing G, Kuhlmann J. Glucuronidation of acetaminophen is independent of UGT1A1 promotor genotype. Int J Clin Pharmacol Ther. 2004 Feb. 42(2):73-7. [Medline].

  61. Birraux J, Menzel O, Wildhaber B, Jond C, Nguyen TH, Chardot C. 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. 2009 Apr 15. 87(7):1006-12. [Medline].

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

  63. Sherbiny HS, Youssef DM, Sherbini AS, El-Behedy R, Sherief LM. High-intensity light-emitting diode vs fluorescent tubes for intensive phototherapy in neonates. Paediatr Int Child Health. 2016 May. 36 (2):127-33. [Medline].

  64. Waterham M, Bhatia R, Donath S, Molesworth C, Tan K, Stewart M. Phototherapy in transport for neonates with unconjugated hyperbilirubinaemia. J Paediatr Child Health. 2016 Jan. 52 (1):67-71. [Medline].

  65. Karakukcu C, Ustdal M, Ozturk A, Baskol G, Saraymen R. Assessment of DNA damage and plasma catalase activity in healthy term hyperbilirubinemic infants receiving phototherapy. Mutat Res. 2009 Nov-Dec. 680(1-2):12-6. [Medline].

  66. Ramy N, Ghany EA, Alsharany W, et al. Jaundice, phototherapy and DNA damage in full-term neonates. J Perinatol. 2015 Nov 19. [Medline].

  67. Kumar P, Chawla D, Deorari A. Light-emitting diode phototherapy for unconjugated hyperbilirubinaemia in neonates. Cochrane Database Syst Rev. 2011 Dec 7. CD007969. [Medline].

  68. Schauer R, Stangl M, Lang T, Zimmermann A, Chouker A, Gerbes AL, et al. Treatment of Crigler-Najjar type 1 disease: relevance of early liver transplantation. J Pediatr Surg. 2003 Aug. 38(8):1227-31. [Medline].

  69. van der Veere CN, Sinaasappel M, McDonagh AF, Rosenthal P, Labrune P, Odièvre M, et al. Current therapy for Crigler-Najjar syndrome type 1: report of a world registry. Hepatology. 1996 Aug. 24(2):311-5. [Medline].

  70. Lysy PA, Najimi M, Stephenne X, Bourgois A, Smets F, Sokal EM. Liver cell transplantation for Crigler-Najjar syndrome type I: update and perspectives. World J Gastroenterol. 2008 Jun 14. 14(22):3464-70. [Medline]. [Full Text].

  71. Ozçay F, Alehan F, Sevmis S, Karakayali H, Moray G, Torgay A, et al. Living related liver transplantation in Crigler-Najjar syndrome type 1. Transplant Proc. 2009 Sep. 41(7):2875-7. [Medline].

  72. Ambrosino G, Varotto S, Strom SC, Guariso G, Franchin E, Miotto D, et al. Isolated hepatocyte transplantation for Crigler-Najjar syndrome type 1. Cell Transplant. 2005. 14(2-3):151-7. [Medline].

  73. Fox IJ, Chowdhury JR. Hepatocyte transplantation. Am J Transplant. 2004. 4 Suppl 6:7-13. [Medline].

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

  75. Dhawan A, Mitry RR, Hughes RD. Hepatocyte transplantation for liver-based metabolic disorders. J Inherit Metab Dis. 2006 Apr-Jun. 29(2-3):431-5. [Medline].

  76. Ribes-Koninckx C, Pareja Ibars E, Agrasot MA, Bonora-Centelles A, Polo Miquel B, Vila Carbó JJ, et al. Clinical outcome of hepatocyte transplantation in four pediatric patients with inherited metabolic diseases. Cell Transplant. 2012 Apr 18. [Medline].

  77. Palmela I, Correia L, Silva RF, et al. Hydrophilic bile acids protect human blood-brain barrier endothelial cells from disruption by unconjugated bilirubin: an in vitro study. Front Neurosci. 2015. 9:80. [Medline].

  78. Woodgate P, Jardine LA. Neonatal jaundice: phototherapy. BMJ Clin Evid. 2015 May 22. 2015:[Medline].

 
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Production of bilirubin.
Enterohepatic circulation of bilirubin.
Conjugation of bilirubin.
 
 
 
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