• Ahsan Rasool Ayub Medical College, Abbottabad
  • Sabir Sabir Clinical Fellow Hepatobiliary Anaesthesia, Toronto East General Hospital, Toronto
  • Muhammad Ashfaq Department of Community Medicine, Ayub Medical College, Abbottabad
  • Umer Farooq Department of Community Medicine, Ayub Medical College, Abbottabad
  • Muhammad Zatmar Khan Ayub Medical College, Abbottabad
  • Faisal Yousaf Khan Ayub Medical College, Abbottabad


Gilbert’s syndrome (often abbreviated as GS) is most common hereditary cause of mild unconjugated (indirect) hyperbilirubinemia. Various studies have been published depicting clinical and pharmacological effects of Gilbert’s syndrome (GS). However GS as a sign of precaution for physician and surgeons has not been clearly established. A systematic study of the available literature was done. Key words of Gilbert’s syndrome, hyperbilirubinemia and clinical and pharmacological aspects of GS were searched using PubMed as search engine. Considering the study done in last 40 years, 375 articles were obtained and their abstracts were studied. The criterion for selecting the articles for through study was based on their close relevance with the topic. Thus 40 articles and 2 case reports were thoroughly studied. It was concluded that Gilbert’s syndrome has immense clinical importance because the mild hyperbilirubinemia can be mistaken for a sign of occult, chronic, or progressive liver disease.GS is associated with lack of detoxification of few drugs. It is related with spherocytosis, cholithiasis, haemolytic anaemia, intra-operative toxicity, irinotecan toxicity, schizophrenia and problems in morphine metabolism. It also has profound phenotypic effect as well. The bilirubin level of a GS individual can rise abnormally high in various conditions in a person having Gilbert’s syndrome. This can mislead the physicians and surgeons towards false diagnosis. Therefore proper diagnosis of GS should be ascertained in order to avoid the concealed adversities of this syndrome.


Walker G, Sherman K, Sanderson S. Editors. Pediatric gastrointestinal disease. 4th ed. Washington: DC Decker Inc; 2004.

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

Farheen S, Sengupta S, Santra A, Pal S, Dhali GK, Chakravorty M. 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;12(14):2269–75.

Avery GB, MacDonald MG, Mullett MD, Seshia MK, editors. Avery's Neonataology. 6th ed. Philadelphia: Lippincott Williams and Wilkins; 2005.

Radu P, Atsmon J. Gilbert’s Syndrome- Clinical and Pharmacological Implications. Isr Med Assoc J 2001;3(8):593–8.

Bosma PJ, Chowdhury JR, Bakker C, Gantla S, de Boer A, Oostra BA, et al. The Genetic Basis of the Reduced Expression of Bilirubin UDP-Glucuronosyltransferase 1 in Gilbert's Syndrome. N Engl J Med 1995;333(18):1171–5.

Nikolac, N. Genetic basis of Gilbert's syndrome. 3. Slovenian Congress of Clinical Chemistry and the 18th International Symposium of Slovenian Association for Clinical Chemistry and Croatian Society of Medical Biochemists. Hrvatska znanstvena bibliografija i MZOS-Svibor. January 2008.

Rawa K, Adamowicz-Salach A, Matysiak M, Trzemecka A, Burzynska B. Coexistence of Gilbert syndrome with hereditary haemolytic anaemias. J Clin Pathol 2012;65(7):663–5.

Carpenter SL, Lieff S, Howard TA, Eggleston B, Ware RE. UGT1A1 promoter polymorphisms and the development of hyperbilirubinemia and gallbladder disease in children with sickle cell anemia. Am J Hematology 2008;83(10):800–3.

del Giudice EM, Perrotta S, Nobili B, Specchia C, d’Urzo G, Iolascon. Coinheritance of Gilbert Syndrome Increases the Risk for Developing Gallstones in Patients With Hereditary Spherocytosis. Blood 1999;94(7):2259–62.

Miyaoka T, Seno H, Maeda T, Itoga M, Horiguchi J. Schizophrenia-associated idiopathic unconjugated hyperbilirubinemia (Gilbert's syndrome): 3 case reports. J Clin Psychiatry 2000;61(4):299–300.

Franson TR, LaBrecque DR, Buggy BP,Harris GJ, Hoffmann RG. Serial bilirubin determinations as a prognostic marker in clinical infections. Am J Med Sci 1989;297(3):149–52.

Claridge LC, Armstrong MJ, Gill PS. Gilbert’s syndrome. BMJ 2011;342:d2293.

Maruo Y, Sato H, Yamano T, Doida Y, Shimada M. Gilbert syndrome caused by a homozygousmissense mutation (Tyr486Asp) of bilirubinUDP-glucuronosyltransferase gene. J Pediatr 1998;132(6):1045–7.

Schmid R. Gilbert's syndrome- a legitimate genetic anomaly? N Engl J Med 1995;333(18):1217–8.

Lankisch TO, Schulz C, Zwingers T, Erichsen TJ, Manns MP, Heinemann V, et al. Gilbert's Syndrome and irinotecan toxicity: combination with UDP-glucuronosyltransferase 1A7 variants increases risk. Cancer Epidemiol Biomarkers Prev 2008;17(3):695–701.

Løtveit T. Acute appendicitis in patients with Gilbert's syndrome. Acta chirurgica scandinavica 1984;151(8):701–2

Malfatti MA, Felton JS. Human UDP-glucuronosyltransferase 1A1 is the primary enzyme responsible for the N-glucuronidation of N-hydroxy-PhIP in vitro. Chem Res Toxicol 2004;17(8):1137–44.

Fuchs C, Mitchell EP, Hoff PM. Irinotecan in the treatment of colorectal cancer. Cancer Treat Rev 2006;32(7):491–503.

Innocenti F, Undevia SD, Iyer L, Chen PX, Das S, Kocherginsky M, et al. Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. J Clin Oncol 2004;22(8):1382–8.

Esteban A, Pérez-Mateo M. Heterogeneity of paracetamol metabolism in Gilbert's syndrome. Eur J Drug Metab Pharmacokinet 1999;24(1):9–13.

Taylor S. Gilbert's syndrome as a cause of postoperative jaundice. Anaesthesia 1984;39(12):1222–4.

Watchko JF. Hyperbilirubinemia and Bilirubin Toxicity in the Late Preterm Infant. Clin Perinatol 2006;33(4):839–52.

Hanks GW, Conno F, Cherny N, Hanna M, Kalso E, McQuay HJ, et al. Morphine and alternative opioids in cancer pain: the EAPC recommendations. Br J Cancer 2001;84(5):587–93.

Knibbe CA, Krekels EH, van den Anker JN, DeJongh J, Santen GW, van Dijk M, et al. Morphine glucuronidation in preterm neonates, infants and children younger than 3 years. Clin Pharmacokinet 2009;48(6):371–85.

Green MD, King CD, Mojarrabi B, Mackenzie PI, Tephly TR. Glucuronidation of amines and other xenobiotics catalyzed by expressed human UDP-glucuronosyltransferase 1A3. Drug Metab Dispos 1998;26(6):507–512.

Nishimura TG, Jackson SH, Cpohen SN. Prolongation of morphine anaesthesia in a patient with Gilbert's disease: report of a case. Can Anaesth Soc J 1973;20(5):709–12.

Skarke C, Schmidt H, Geisslinger G, Darimont J, örn Lötsch. Pharmacokinetics of morphine are not altered in subjects with Gilbert's syndrome. Br J Clin Pharmacol 2003;56(2):228–31.

Libor V, Jirsa Jr M, Brodanová M, Kaláb M, Mareček Z, Danzig V, et al. Gilbert syndrome and ischemic heart disease: a protective effect of elevated bilirubin levels. Atherosclerosis 2002;160(2):449–56.

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

Muchova L, Kraslova I, Lenicek M, Vitek L. Gilbert’s syndrome-myths and reality. Cas Lek Cesk 2004;143(6):375–80.

Saki F, Hemmati F, Haghighat M. Prevalence of Gilbert syndrome in parents of neonates with pathologic indirect hyperbilirubinemia. Ann Saudi Med 2011;31(2):140–4.

Sieg A, Stiehl A, Raedsch R, Ullrich D, Messmer B, Kommerell B. Gilbert's syndrome: diagnosis by typical serum bilirubin pattern. Clin Chim Acta 1986;154(1):41–7.

Thomsen HF, Hardt F, Juhl E. Diagnosis of Gilbert's Syndrome Reliability of the Caloric Restriction and Phenobarbital Stimulation Tests. Scand J Gastroenterol 1981;16(5):699–703.

Ranjan RV,Ramachandran TR, Veliath DG, Coelho D. Perioperative management of a patient with Gilberts syndrome and rheumatic heart disease. Saudi J Anaesth 2012;6(3):289–91.

Chandra A, Banavaliker JN, Dixit RM. Gilbert’s syndrome. Anaesth Pain Intensive Care 2012;16(2):195–7.

Nag DS, Niraj Sinha N, Samaddar DP, and Mahanty PR. General anesthesia in a patient with Gilbert's syndrome. J Anaesthesiol Clin Pharmacol 2011;27(2):253–5.

Costa E, Vieira E, dos Santos R. The polymorphism c.-3279T> G in the phenobarbital-responsive enhancer module of the bilirubin UDP-glucuronosyltransferase gene is associated with Gilbert syndrome. Clin Chem 2005;51(11):2204–6.



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