Blood serum metabolomic assessment — a perspective diagnostic method for non-alcoholic fatty liver disease in men
- Authors: Abatsieva M.P.1, Bakulin I.G.1, Sitkin S.I.1, Vakhitov T.Y.2, Demyanova E.V.2
-
Affiliations:
- North-Western State Medical University named I.I. Mechnikov
- State Research Institute of Highly Pure Biopreparations FMBA of Russia
- Issue: Vol 10, No 4 (2018)
- Pages: 5-14
- Section: Original research
- URL: https://journal-vniispk.ru/vszgmu/article/view/10394
- DOI: https://doi.org/10.17816/mechnikov20181045-14
- ID: 10394
Cite item
Full Text
Abstract
Diagnosis of liver disease in particular non-alcoholic fatty liver disease (NAFLD) is largely determined by methods that are informative, safe, non-invasive, highly sensitive and can be used in all patients without exception. One of these methods is gas chromatography-mass spectrometry (GC-MS). Our study presents the results of serum metabolome assessment by the GC-MS method in male patients for the diagnosis of NAFLD at the stage of non-alcoholic steatohepatitis. In serum samples obtained from 25 patients, 319 compounds were identified, among them 109 were annotated. In patients with NAFLD, there was a significant increase in indole carboxylic and fatty acids, hypoxanthine, hydroxycarboxylic and phenylcarboxylic acids. The results of the study showed that low-molecular metabolites in particular reduced levels of 4-hydroxybutyric acid and 360 compounds suggests possible influence of metabolites on the pathogenesis of NAFLD, and an elevated level of sugar alcohol suggests a possible damaging effect on liver cells. For the detected compounds 4-hydroxybutyric acid, compound-360 and sugar alcohol, high specificity and sensitivity values, high confidence intervals and AUC values were shown, which indicates the possibility of using mass spectrometry analysis of plasma metabolome at high levels of steatohepatitis with high degree of reliability and probability.
Full Text
##article.viewOnOriginalSite##About the authors
Madina P. Abatsieva
North-Western State Medical University named I.I. Mechnikov
Author for correspondence.
Email: madina.abacieva@mail.ru
ORCID iD: 0000-0002-1989-7546
SPIN-code: 6659-6646
ResearcherId: U-7829-2018
https://vk.com/id157820308
post-graduate student, physician
Russian Federation, 41, Kirochnaya street, Saint-Petersburg, 191015Igor G. Bakulin
North-Western State Medical University named I.I. Mechnikov
Email: igbakulin@yandex.ru
ORCID iD: 0000-0002-6151-2021
SPIN-code: 5283-2032
Scopus Author ID: 6603812937
ResearcherId: P-4453-2014
Dean of the medical faculty, Professor, doctor of medical Sciences, head of the Department of propaedeutics of internal diseases of gastroenterology and dietetics named after S. M. Rys
Russian Federation, 41, Kirochnaya street, Saint-Petersburg, 191015Stanislav I. Sitkin
North-Western State Medical University named I.I. Mechnikov
Email: sitkins@yandex.ru
ORCID iD: 0000-0003-0331-0963
SPIN-code: 3961-8815
Scopus Author ID: 6603071466
ResearcherId: O-7557-2014
candidate of medical Sciences, associate Professor of the Department of propaedeutics of internal diseases of gastroenterology and dietetics named after S. M. Rys
Russian Federation, 41, Kirochnaya street, Saint-Petersburg, 191015Timur Ya. Vakhitov
State Research Institute of Highly Pure Biopreparations FMBA of Russia
Email: t.ya.vakhitov@hpb.spb.ru
Scopus Author ID: 55406626900
Head of Laboratory, Doctor of Biological Sciences
Russian Federation, 7, Pudozhskaya ul., Saint Petersburg, 197110Elena V. Demyanova
State Research Institute of Highly Pure Biopreparations FMBA of Russia
Email: e.v.demyanova@hpb.spb.ru
ORCID iD: 0000-0002-1872-3464
Scopus Author ID: 57194047975
ResearcherId: P-9211-2017
Deputy Head of Laboratory, Candidate of Pharmacological Sciences
Russian Federation, 7, Pudozhskaya ul., Saint Petersburg, 197110References
- Бакулин И.Г., Сандлер Ю.Г., Кейян В.А., и др. Оценка стеатоза печени с помощью неинвазивного метода: миф или реальность? // Доктор.Ру. Гастроэнтерология. – 2015. – № 12(113). – С. 57–64. [Bakulin IG, Sandler YuG, Keiyan VA., et al. Noninvasive Assessment of Hepatic Steatosis: Myth or Reality? Doctor.Ru. Gastroenterology. 2015;(12(113)):57-64. (In Russ.)]
- Бакулин И.Г., Абациева М.П. Неинвазивные методы в диагностике неалкогольной жировой болезни печени // Медико-социальная экспертиза и реабилитация. – 2017. – Т. 20. – № 2. – С. 107–112. [Bakulin IG, Abatsieva MP. Noninvasive methods in the diagnosis of non-alcoholic fatty liver disease. Medical-social examination and rehabilitation. 2017;20(2):107-112. (In Russ.)]. https://doi.org/10.18821/1560-9537-2017-20-2-107-112.
- Estes C, Razavi H, Loomba R, et al. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology (Baltimore, Md). 2018;67(1):123-133. https://doi.org/10.1002/hep.29466.
- Doulberis M, Kotronis G, Gialamprinou D, et al. Non-alcoholic fatty liver disease: an update with special focus on the role of gut microbiota. Metabolism. 2017;71:182-197. https://doi.org/10.1016/j.metabol.2017.03.013.
- Шиповская А.А., Ларина Н.А., Дуданова О.П. Клинические особенности неалкогольной жировой болезни печени в гендерном аспекте // Journal of biomedical technologies. – 2016. – № 1. – С. 35–40. [Shipovskaya AA, Larina NA, Dudanova OP. Clinical features of nonalcoholic fatty liver disease: gender aspect. Journal of biomedical technologies. 2016;(1):35-40. (In Russ.)]. https://doi.org/10.15393/j6.art.2016.3522.
- Molnar MZ, Joglekar K, Jiang Y, et al. Association of Pre-Transplant Renal Function with Liver Graft and Patient Survival after Liver Transplantation in Patients with Nonalcoholic Steatohepatitis. Global NAFLD Consortium. Liver Transpl. 2018 Oct 28. https://doi.org/10.1002/lt.25367.
- Neuman MG, Cohen LB, Nanau RM. Biomarkers in nonalcoholic fatty liver disease. Can J Gastroenterol Hepatol. 2014;28(11):607-618. https://doi.org/1155/2014/ 757929.
- Ситкин С.И., Калинина Е.А., Волкунович Т.А., и др. Метаболомика — новый подход к диагностике заболеваний на молекулярном уровне // Лечение и профилактика. – 2013. – № 2 (6). – С. 117–124. [Sitkin SI, Kalinina YeA, Volkunovich TA, et al. The metabolomics as a new approach to diagnostic of diseases on the molecular level. Disease treatment and prevention. 2013;(2(6)):117-124. (In Russ.)]
- Loomba R, Quehenberger O, Amado A, et al. Polyunsaturated fatty acid metabolites as novel lipidomic biomarkers for noninvasive diagnosis of nonalcoholic steatohepatitis. Journal of Lipid Research. 2015 Jan;56(1):185-192. https://doi.org/10.1194/jlr.P055640.
- Tokushige K, Hashimoto E, Kodama K, et al. Serum metabolomic profile and potential biomarkers for severity of fibrosis in nonalcoholic fatty liver disease. J Gastroenterol. 2013;48(12):1392-1400. https://doi.org/10.1007/s00535-013-0766-5.
- Kalhan SC, Guo L, Edmison J, et al. M. Plasma metabolomic profile in nonalcoholic fatty liver disease. Metabolism. 2011;60:404-413. https://doi.org/10.1016/j.metabol.2010.03.006.
- Safaei A, Oskouie AA, Mohebbi SR, et al. Metabolomic analysis of human cirrhosis, hepatocellular carcinoma, non-alcoholic fatty liver disease and non-alcoholic steatohepatitis diseases. Gastroenterol Hepatol Bed Bench. 2016;9(3):158. PMC4947130.
- Li L, Huang L, Lemos HP, et al. Altered tryptophan metabolism as a paradigm for good and bad aspects of immune privilege in chronic infl ammatory diseases. Front Immunol. 2012;3:109. https://doi.org/10.3389/fimmu.2012.00109.
- Vanholder R, Schepers E, Pletinck A, et al. An update on protein-bound uremic retention solutes. J Ren Nutr. 2012;22(1):90-4. https://doi.org/10.1053/j.jrn. 2011.10.026.
- Raman M, Ahmed I, Gillevet PM, et al. Fecal microbiome and volatile organic compound metabolome in obese humans with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2013;11(7):868-75.e1-3. https://doi.org/10.1016/j.cgh.2013.02.015. Epub 2013 Feb 27.
- Звенигородская Л.А., Черкашова Е.А., Самсонова Н.Г., и др. Целесообразность применения пробиотиков в лечении атерогенной дислипидемии // Эффективная фармакотерапия. – 2011. – № 7. – С. 46–52. [Zvenigorodskaya LA, Cherkashova YA, Samsonova NG, et al. The expediency of using probiotics in the treatment of atherogenic dyslipidemia. Effective pharmacotherapy. 2011;(7):46-52. (In Russ.)]
- Bessone F, Razori MV, Roma MG. Molecular pathways of nonalcoholic fatty liver disease development and progression. Cell Mol Life Sci. 2018 Oct 20. https://doi.org/10.1007/s00018-018-2947-0.
- Wu H, Xue R, Dong L, et al. Metabolomic profiling of human urine in hepatocellular carcinoma patients using gas chromatography/mass spectrometry. Anal Chim Acta. 2009;648(1):98-104. https://doi.org/10.1016/j.aca.2009.06.033. Epub 2009 June 21.
- Shinka T, Inoue Y, Ohse M, et al. Rapid and sensitive detection of urinary 4-hydroxybutyric acid and its related compounds by gas chromatography-mass spectrometry in a patient with succinic semialdehyde dehydrogenase deficiency. J Chromatogr B Analyt Technol Biomed Life Sci.2002;776(1):57-63. https://doi.org/10.1016/s1570-0232(02)00126-5.
- Beloborodova N, Bairamov I, Olenin A, et al. Effect of phenolic acids of microbial origin on production of reactive oxygen species in mitochondria and neutrophils. J Biomed Sci. 2012;19:89. https://doi.org/10.1186/1423-0127-19-89.
Supplementary files
