Gilbert’s syndrome - bright and dark sides of the disease - literature review
DOI:
https://doi.org/10.12775/JEHS.2024.63.011Keywords
Gilbert’s syndrome, bilirubin, UDP-glucuronosyltransferase, Gilbert’s syndrome harmful and protective aspects, iatrogenic Gilbert’s syndromeAbstract
Gilbert’s syndrome is the most common inherited jaundice worldwide. It affects 5-10% of the population. It is caused by a mutation of the UGT1A1 gene, which results in impaired bilirubin metabolism. It is a benign disease and does not affect the life expectancy of patients. Patients with Gilbert’s syndrome should be alert to factors that exacerbate the course of the disease, interactions with medications taken and possible comorbidities such as hemolytic anemia, cholelithiasis or schizophrenia. However, it is the responsibility of physicians with such patients under their care to properly educate patients. Gilbert’s syndrome carries not only the consequences associated with the mutation, but also has many benefits that patients may not be fully aware of. Mildly elevated bilirubin levels have an antioxidant and anti-inflammatory effect, which prevents the development of lifestyle diseases and cancer. Ongoing clinical trials suggest that this could be a great step toward new treatments for diseases affecting the entire human population.
PURPOSE OF THE WORK: This review paper aims to show Gilbert’s syndrome as a multifaceted disease and to sensitize doctors' attention to patients with the described mutation.
MATERIALS AND METHODS: An analysis of papers available in PubMed and Google Scholar was performed using the following key words: Gilbert’s syndrome, bilirubin, UDP-glucuronosyltransferase, Gilbert’s syndrome harmful and protective aspects, iatrogenic Gilbert’s syndrome
RESULTS: The result of the work is to present Gilbert’s syndrome as a disease that carries medical problems directly related to the mutation, but also, in some cases, has a protective effect on affected individuals. The work highlights the complexity of the problem.
References
King D, Armstrong M. Overview of Gilbert’s syndrome. Drug Ther Bull. luty 2019;57(2):27–31.
Fretzayas A, Moustaki M, Liapi O, Karpathios T. Eponym: Gilbert syndrome. Eur J Pediatr. styczeń 2012;171(1):11–5.
Erlinger S, Arias IM, Dhumeaux D. Inherited Disorders of Bilirubin Transport and Conjugation: New Insights Into Molecular Mechanisms and Consequences. Gastroenterology. czerwiec 2014;146(7):1625–38.
Horsfall LJ, Nazareth I, Pereira SP, Petersen I. G ilbert’s syndrome and the risk of death: A population‐based cohort study. J Gastroenterol Hepatol. październik 2013;28(10):1643–7.
Wagner KH, Shiels RG, Lang CA, Seyed Khoei N, Bulmer AC. Diagnostic criteria and contributors to Gilbert’s syndrome. Crit Rev Clin Lab Sci. 17 luty 2018;55(2):129–39.
Vitek L, Bellarosa C, Tiribelli C. Induction of Mild Hyperbilirubinemia: Hype or Real Therapeutic Opportunity? Clin Pharmacol Ther. wrzesień 2019;106(3):568–75.
Zöhrer PA, Hana CA, Seyed Khoei N, Mölzer C, Hörmann-Wallner M, Tosevska A, i in. Gilbert’s Syndrome and the Gut Microbiota – Insights From the Case-Control BILIHEALTH Study. Front Cell Infect Microbiol. 16 wrzesień 2021;11:701109.
Thoguluva Chandrasekar V, Faust TW, John S. Gilbert Syndrome. W: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cytowane 19 styczeń 2024]. Dostępne na: http://www.ncbi.nlm.nih.gov/books/NBK470200/
Zespół Gilberta – standard diagnostyczno-terapeutyczny - Standardy medyczne [Internet]. [cytowane 20 styczeń 2024]. Zespół Gilberta – standard diagnostyczno-terapeutyczny - Standardy Medyczne. Dostępne na: https://www.standardy.pl/artykuly/id/1497
Gil J, Sąsiadek MM. Gilbert syndrome: the UGT1A1 *28 promoter polymorphism as a biomarker of multifactorial diseases and drug metabolism. Biomark Med. kwiecień 2012;6(2):223–30.
Kundur AR, Santhakumar AB, Bulmer AC, Singh I. Mildly elevated unconjugated bilirubin is associated with reduced platelet activation-related thrombogenesis and inflammation in Gilbert’s syndrome. Platelets. 17 listopad 2017;28(8):779–85.
Vitek L, Ostrow J. Bilirubin Chemistry and Metabolism; Harmful and Protective Aspects. Curr Pharm Des. 1 wrzesień 2009;15(25):2869–83.
Rawa K, Adamowicz-Salach A, Matysiak M, Trzemecka A, Burzynska B. Coexistence of Gilbert syndrome with hereditary haemolytic anaemias. J Clin Pathol. lipiec 2012;65(7):663–5.
Burchell B, Hume R. Molecular genetic basis of Gilbert’s syndrome. J Gastroenterol Hepatol. październik 1999;14(10):960–6.
De Morais SMF, Uetrecht JP, Wells PG. Decreased glucuronidation and increased bioactivation of acetaminophen in Gilbert’s syndrome. Gastroenterology. luty 1992;102(2):577–86.
Vítek L, Tiribelli C. Gilbert’s syndrome revisited. J Hepatol. październik 2023;79(4):1049–55.
Strassburg CP. Hyperbilirubinemia syndromes (Gilbert-Meulengracht, Crigler-Najjar, Dubin-Johnson, and Rotor syndrome). Best Pract Res Clin Gastroenterol. październik 2010;24(5):555–71.
Tóth C, Clemens Z. Gilbert’s Syndrome Successfully Treated with the Paleolithic Ketogenic Diet. Am J Med Case Rep. 9 kwiecień 2015;3(4):117–20.
Tsezou A, Tzetis M, Giannatou E, Spanos I, Roma E, Fretzayas A, i in. Gilbert Syndrome as a Predisposing Factor for Cholelithiasis Risk in the Greek Adult Population. Genet Test Mol Biomark. luty 2009;13(1):143–6.
Li M, Chan WW, Zucker SD. Association Between Atazanavir‐Induced Hyperbilirubinemia and Cardiovascular Disease in Patients Infected with HIV. J Am Heart Assoc. 6 październik 2020;9(19):e016310.
Kang LL, Ma YJ, Zhang HD. Carbon monoxide breath test assessment of mild hemolysis in Gilbert’s syndrome. Medicine (Baltimore). luty 2020;99(7):e19109.
Miyaoka T, Seno H, Itoga M, Iijima M, Inagaki T, Horiguchi J. Schizophrenia-Associated Idiopathic Unconjugated Hyperbilirubinemia (Gilbert’s Syndrome). J Clin Psychiatry. 15 listopad 2000;61(11):868–71.
Vítek L. Bilirubin as a predictor of diseases of civilization. Is it time to establish decision limits for serum bilirubin concentrations? Arch Biochem Biophys. wrzesień 2019;672:108062.
Wang X, Chowdhury JR, Chowdhury NR. Bilirubin metabolism: Applied physiology. Curr Paediatr. luty 2006;16(1):70–4.
Bulmer AC, Blanchfield JT, Toth I, Fassett RG, Coombes JS. Improved resistance to serum oxidation in Gilbert’s syndrome: A mechanism for cardiovascular protection. Atherosclerosis. sierpień 2008;199(2):390–6.
Kundur AR, Singh I, Bulmer AC. Bilirubin, platelet activation and heart disease: A missing link to cardiovascular protection in Gilbert’s syndrome? Atherosclerosis. marzec 2015;239(1):73–84.
Schwertner HA, Vítek L. Gilbert syndrome, UGT1A1*28 allele, and cardiovascular disease risk: Possible protective effects and therapeutic applications of bilirubin. Atherosclerosis. maj 2008;198(1):1–11.
Strassburg CP. Gilbert-Meulengracht’s syndrome and pharmacogenetics: is jaundice just the tip of the iceberg? Drug Metab Rev. luty 2010;42(1):168–81.
Wagner KH, Seyed Khoei N, Hana C, Doberer D, Marculescu R, Bulmer A, i in. Oxidative Stress and Related Biomarkers in Gilbert’s Syndrome: A Secondary Analysis of Two Case-Control Studies. Antioxidants. 15 wrzesień 2021;10(9):1474.
Wallner M, Bulmer AC, Mölzer C, Müllner E, Marculescu R, Doberer D, i in. Haem catabolism: a novel modulator of inflammation in G ilbert’s syndrome. Eur J Clin Invest. wrzesień 2013;43(9):912–9.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Katarzyna Beutler, Jędrzej Lewandowski
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 649
Number of citations: 0