Peculiarities of clinical manifestations and comorbidities in adult patients with Gilbert’s syndrome
Abstract. The high prevalence of Gilbert’s syndrome (GS) in the Russian population and its clinical polymorphism necessitate a thorough study of associated conditions and diseases. The most common complaints with which patients seek medical care, as well as possible correlations between bilirubin levels and comorbidities, require clarification. The question of the presence of gender differences in the structure of concomitant clinical symptoms in GS is of particular interest. The aim: to identify the clinical features, frequency, and spectrum of comorbidities in adult patients with GS. Material and methods. A retrospective study included 53 patients (24 male and 29 female individuals, median age 40 years) with benign hyperbilirubinemia (GS). Results. All subjects with GS had gastrointestinal complaints. Approximately half of the patients had GS combined with gastroesophageal reflux disease and irritable bowel syndrome (56.6 and 47.2%, respectively). Dyspeptic symptoms were present in 90.6% of the subjects. Association between biliary sludge and gallbladder dysfunction was statistically significant (p <0.05). Hepatic steatosis was diagnosed in 20.8% of patients, with a significant association with obesity (p < 0.01). GS was combined with cholelithiasis in a third of the cases, and 7 subjects (13.7%) had a history of cholecystectomy. Chronic gastritis associated with Н. рylori was diagnosed in 12 patients (22.6%), and gastric ulcer and duodenal ulcer were diagnosed in 3 (5.7%) persons. Individuals with the homozygous GS genotype (7TA/7TA) had higher bilirubin levels (38.2 versus 27.4 μmol/L in heterozygous carriers; p <0.01). Conclusion. GS is a common hereditary condition that requires dynamic monitoring. In adult patients with GS, episodes of jaundice are accompanied by a variety of clinical manifestations of dyspeptic nature, and among gastrointestinal diseases, gastroesophageal reflux disease, irritable bowel syndrome, gallbladder dysfunction, and cholelithiasis are most often diagnosed. No gender differences in the pattern of complaints were identified in patients with GS.A.G. Kononova, S.V. Kolbasnikov, E.V. Mashkina, G.D. Bolkhovitin
Keywords
Gilbert’s syndrome
benign hyperbilirubinemia
comorbid conditions
References
1. De Silva AP, Nuwanshika N, Niriella MA, de Silva HJ. Gilbert’s syndrome: The good, the bad and the ugly. World J Hepatol 2025;17(2):98503.
PMID: 40027563. https://doi.org/10.4254/wjh.v17.i2.98503
2. Poynard T, Deckmyn O, Peta V, Sakka M, Lebray P, Moussalli J et al.; FibroFrance Group. Clinical and genetic definition of serum bilirubin levels for the diagnosis of Gilbert syndrome and hypobilirubinemia. Hepatol Commun. 2023;7(10):e0245.
PMID: 37738404. PMCID: PMC10519483. https://doi.org/10.1097/HC9.0000000000000245
3. Grant LM, Faust TW, Thoguluva Chandrasekar V, John S. Gilbert syndrome. 2024 Oct 5. In: StatPearls (Internet). Treasure Island (FL): StatPearls Publishing; 2026 Jan–. PMID: 29262099.
4 Ivanov A, Semenova E. Gilbert’s syndrome, bilirubin level and UGT1A1∗28 genotype in men of North-West region of Russia. J Clin Exp Hepatol. 2021;11(6):691–99.
PMID: 34866848. PMCID: PMC8617539. https://doi.org/10.1016/j.jceh.2021.01.006
5. Блинов Д.Е., Огурцов П.П., Кухарева Е.И. Новый взгляд на синдром Жильбера. Вестник последипломного медицинского образования. 2020;(1):47–49. (Blinov DE, Ogurtsov PP, Kukhareva EI. A new look at Gilbert syndrome. Vestnik poslediplomnogo meditsinskogo obrazovaniya = Journal of Postgraduate Medical Education. 2020;(1):47–49 (In Russ.)). EDN: ISHSRO.
6. Radlovic N, Lekovic Z, Mladenovic M, Ristic D, Radlovic V, Lekic V et al. (Gilbert’s syndrome in children – our experience. Srp Arh Celok Lek, 2007;135(5–6):317–20 (In Serbian)).
PMID: 17633320. https://doi.org/10.2298/sarh0706317r
7. Дубровина Г.М., Ботвиньев О.К., Колотилина А.И. Сочетание синдрома Жильбера с заболеваниями желудочно-кишечного тракта. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2014;24(3):13–21. (Dubrovina GM, Botvinev OK, Kolotilina AI. Combination of Gilbert’s syndrome with gastrointestinal diseases. Rossiyskiy zhurnal gastroenterologii, gepatologii, koloproktologii = Russian Journal of Gastroenterology, Hepatology, Proctology. 2014;24(3):13–21 (In Russ.)). EDN: SIVCTV.
8. Завтур В.В., Халикова А.Р. Синдром Жильбера у детей: почему это синдром, а не болезнь? В сб.: Медицина будущего-2025: материалы Всероссийского научного форума с международным участием, Тюмень, 27–29 марта 2025 года. Тюмень: РИЦ «Айвекс». 2025; 289 с. (Zavtur VV, Khalikova AR. Gilbert’s syndrome in children: Why is it a syndrome and not a disease? In: Medicine of the Future-2025: Proceedings of the All-Russian Scientific Forum with international participation, Tyumen, March 27–29, 2025. Tyumen: Ivex Advertising and Publishing Center. 2025; p. 289 (In Russ.)). EDN: AWANGG.
9. Драпкина О.М., Кравченко А.Я., Будневский А.В., Концевая А.В., Ряскина М.С., Черник Т.А. Билирубин и сердечно-сосудистый риск. Российский кардиологический журнал. 2021;26(9):116–121. (Drapkina OM, Kravchenko AYa, Budnevsky AV, Kontsevaya AV, Ryaskina MS, Chernik TA. Bilirubin and cardiovascular risk. Rossiyskiy kardiologicheskiy zhurnal = Russian Journal of Cardiology. 2021;26(9):116–121 (In Russ.)).
EDN: FGGLKB. https://doi.org/10.15829/1560-4071-2021-4511
10. Freisling H, Seyed Khoei N, Viallon V, Wagner KH. Gilbert’s syndrome, circulating bilirubin and lung cancer: A genetic advantage? Thorax. 2020;75(11):916–17.
PMID: 33023993. https://doi.org/10.1136/thoraxjnl-2020-215642
11. Vítek L, Tiribelli C. Gilbert’s syndrome revisited. J Hepatol. 2023;79(4):1049–55.
PMID: 37390966. https://doi.org/10.1016/j.jhep.2023.06.004
12. Мельникова Л.И., Ильченко Л.Ю., Дунаева Е.А., Козицына М.В., Дрибноходова О.П., Миронов К.О. Выявление синдрома Жильбера методом пиросеквенирования у пациентов в реальной клинической практике. Архивъ внутренней медицины. 2019;9(6):475–482. (Melnikova LI, Ilchenko LYu, Dunaeva EA, Kozitsyna MV, Dribnokhodova OP, Mironov KO. Diagnosis of Gilbert’s syndrome via pyrosequencing in clinical practice. Arkhiv vnutrenney meditsiny = The Russian Archives of Internal Medicine. 2019;9(6):475–482 (In Russ.)).
EDN: NYQZLP. https://doi.org/10.20514/2226-6704-2019-9-6-475-482
13. Сорокин А.С., Халтурина Д.А., Соломатников И.А. Распространенность артериальной гипертонии в России в 2021–2024 гг. Современные проблемы здравоохранения и медицинской статистики. 2025;(4):400–420. (Sorokin AS, Khaltourina DA, Solomatnikov IA. Prevalence of arterial hypertension in Russia in 2021–2024. Sovremennyye problemy zdravookhraneniya i meditsinskoy statistiki = Current Problems of Health Care and Medical Statistics. 2025;(4):400–420 (In Russ.)).
EDN: WSKAYE. https://doi.org/10.24412/2312-2935-2025-4-400-420
14. Beaney T, Schutte AE, Stergiou GS, Borghi C, Burger D, Charchar F et al.; MMM Investigators May Measurement Month 2019: The Global Blood Pressure Screening Campaign of the International Society of Hypertension. Hypertension. 2020;76(2):333–41.
PMID: 32419505. https://doi.org/10.1161/HYPERTENSIONAHA.120.14874
15. Дедов И.И., Шестакова М.В., Викулова О.К., Железнякова А.В., Исаков М.А., Сазонова Д.В., Мокрышева Н.Г. Сахарный диабет в Российской Федерации: динамика эпидемиологических показателей по данным Федерального регистра сахарного диабета за период 2010–2022 гг. Сахарный диабет. 2023;26(2):104–123. (Dedov II, Shestakova MV, Vikulova OK, Zheleznyakova AV, Isakov MA, Sazonova DV, Mokrysheva NG. Diabetes mellitus in the Russian Federation: Dynamics of epidemiological indicators according to the Federal Register of Diabetes Mellitus for the period 2010–2022. Sakharnyy diabet = Diabetes Mellitus. 2023;26(2):104–123 (In Russ.)).
EDN: DVDJWJ. https://doi.org/10.14341/DM13035
About the Authors
Alla G. Kononova, MD, PhD (Medicine), associate professor, associate professor of the Department of general medical practice and family medicine, Tver State Medical University, Tver, Russian Federation.E-mail: allakononova@mail.ru
ORCID: https://orcid.org/0000-0002-4525-0885. Scopus ID: 57189609067. eLibrary SPIN: 3812-6708
Sergey V. Kolbasnikov, MD, Dr. Sci. (Medicine), professor, head of the Department of general medical practice and family medicine, Tver State Medical University, Tver, Russian Federation.
E-mail: kaf-obschvr@tvgmu.ru
ORCID: https://orcid.org/0000-0002-9223-0457. Scopus ID: 6602366710. eLibrary SPIN: 2127-3801
Ekaterina V. Mashkina, MD, second-year clinical resident of the Department of general medical practice and family medicine, Tver State Medical University, Tver, Russian Federation.
E-mail: ekmashkina@mail.ru
Gleb D. Bolkhovitin, fifth-year student of the faculty of general medicine, Tver State Medical University, Tver, Russian Federation.
E-mail: mr.bgt2003@mail.ru
Similar Articles
