The using of genetic markers as a possibility of predicting the rate of progress of liver fibrosis in patients with chronic hepatitis B

Authors

DOI:

https://doi.org/10.26641/2307-0404.2023.3.288931

Keywords:

chronic hepatitis B, liver fibrosis, prognosis, allelic polymorphism of cytokine genes SMAD 7 (rs4939827), TNFα (rs1800620), IL-10 (rs1800896), IL-4 (rs2243250), antifibrotic therapy, bicyclol

Abstract

According to recent WHO estimates, chronic HBV infection is one of the leading causes of death and disability in patients with infectious diseases. From 780 thousand to 1 million deaths are annually recorded in the world as a result of cirrhosis of the liver and hepatocellular carcinoma. Pathogenetic features of the course and outcomes of chronic hepatitis B are determined by the immunological, genetic factors of the host, as well as the molecular biological structure of the virus. The aim of the work was to study the interaction of polymorphic loci of the cytokine genes SMAD 7 (rs4939827), TNFα (rs1800620), IL-10 (rs1800896), IL-4 (rs2243250) and the degree of structural changes in the liver based on the non-invasive Fibrotest technique in patients with chronic hepatitis B as part of a search for possible predictors of predisposition to the rapid progression of liver fibrosis. The study included 82 patients with chronic hepatitis B. Assessment of morphological changes (stage of fibrosis) was carried out by the method of non-invasive diagnosis of FibroScan, which is an alternative to puncture biopsy of the liver. It has been suggested that homozygous alleles СС IL-4 (rs2243250), GG TNFα (rs1800620), СС SMAD family member 7 (rs4939827) have a protective effect on the course of chronic hepatitis B, as these variants of allelic polymorphism of cytokine genes were found mainly in patients with CHB with a degree of fibrosis F0-F1. The heterozygous genotypes СТ IL-4 (rs2243250) and GA TNFα (rs1800620), the mutant homozygous ТТ SMAD family member 7 (rs4939827) have a profibrotic effect on the course of chronic hepatitis B, as they are found mainly in patients with chronic hepatitis B with degree of fibrosis F3. The established relationship between the liver fibrosis stage according to the METAVIR scale and the polymorphism of the cytokine genes SMAD 7 (rs4939827), TNFα (rs1800620) and IL-4 (rs2243250) made it possible to create a prognostic scale for assessing the individual risk of rapid progression of liver fibrosis. The proposed scale, due to a comprehensive assessment of the polymorphism of cytokine gene alleles and the stage of liver fibrosis using the METAVIR scale, makes it possible to carry out an individual assessment of the risk of progression of chronic hepatitis and, possibly, draw up a personalized treatment plan for the patient. Coding of the studied polymorphisms and subsequent counting can be automated, which does not require significant financial investments. The possibilities of the prognostic scale are proven on the example of a group of patients who received the antifibrotic agent bicyclol in comparison with the control group.

References

[Public Health Center. Viral hepatitis 2020. Report]. [Internet]. Kyiv; 2021 [cited 2022 Dec 12]. 24 р. Ukrainian. Available from: https://phc.org.ua/sites/default/files/users/user90/A4_zvit_gepatit1021_online_zamina.pdf

Pashkov IV, Fedorova SF. [Immediate results of treatment with nucleotide/nucleoside analogues in patients with chronic hepatitis В]. Mizhnarodnyi medychnyi zhurnal. 2019;2(25):76-80. Ukrainian.

Lytovka SL, Batsiura HV, Berezenko VS, Bidovanets OIu, Holubovska OA, Dyba MB, et al. [Viral hepatitis B evidence-based clinical guidelines]. [Internet]. 2020. [cited 2022 Dec 12]. 159 р. Ukrainian. Available from: https://www.dec.gov.ua/wp-content/uploads/2021/01/2021_48_49_kn_vgv.pdf

European association for study of the liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatology. 2017;67:370-98. doi: https://doi.org/10.1016/j.jhep.2017.03.021

Herasun BA, Herasun OB. [Mutations of hepatitis B virus]. Hepatolohiia. 2019;2:45-52. Ukrainian.

Afify SM, Hassan G, Osman A, et al. Metastasis of Cancer Stem Cells Developed in the Microenvironment of Hepatocellular Carcinoma. Bioengineering (Basel). 2019;6(3):E73. doi: https://doi.org/10.3390/bioengineering6030073

Calès P, Boursier J, Oberti F, et al. A 176 single blood test adjusted for different liver fibrosis targets im-proves fibrosis staging and especially cirrhosis diagnosis. Hepatol Commun. 2018;2(4):455-66. doi: https://doi.org/10.1002/hep4.1161

Moroz LV, Bondaruk IYu. [Diagnostic value of non-invasive markers of liver fibrosis in patients with chronic viral hepatitis C]. Hepatolohiia. 2019;2(44):28-34. Ukrainian.

Karsdal MA, et al. Collagen biology and non‐invasive biomarkers of liver fibrosis. Liver Int. 2020;40:736-50. doi: https://doi.org/10.1111/liv.14390

Usychenko EN, Usychenko EM. [Model of prediction of the progress of liver fibrosis on the basis of biochemical and genetic criteria in patients with chronic hepatitis С]. Georgian medical news. 2020;11(308):63-7. Russian.

Capelle C, Spit M, Dijke P. Current perspectives on inhibitory SMAD7 in health and disease. Critical Reviews in Biochemistry and Molecular Biology. 2020;55(6):691-715. doi: https://doi.org/10.1080/10409238.2020.1828260

[Unified clinical protocol of primary, secondary (specialized), tertiary (highly specialized) medical care for viral hepatitis B in adults. Order of the Ministry of Health of Ukraine 2016 Jun 21 No. 613]. Kyiv; 2016. 46 p. Ukrainian.

Lioznov DA, Geivandova NI, Morozov VG, et al. [Evaluation of the effectiveness of the original hepatoprotective drug Bicyclol in patients with chronic viral hepatitis C]. Ukrainskyi medychnyi chasopys. 2014;6(104):14-7. Russian.

[New opportunities in the treatment of chronic hepatitis. Bicyclol – 15 years of effective therapy!] [Internet]. [cited 2022 Dec 12]. Ukrainian. Available from: http://bicyclol.com/wp-content/uploads/reprint_Bicyclol.indd_.pdf

Hurianov VH, Liakh YuYe, Parii VD, Korotkyi OV, Chalyi OV, Chalyi KO, et al. [Handbook of biostatistics. Analysis of medical research results in the EZR package (R–statistics)]. Kyiv: Vistka; 2018. 208 р. Ukrainian.

Moroz LV, Yatsyk IV, Ocheredko OM, Livshyts LA, Pampukha VM, inventors. [The method of predicting the rate of progression of liver fibrosis in patients with chronic hepatitis C]. Patent Ukrainy No. u201503954. 2015 Dec 10. Ukrainian.

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Published

2023-09-29

How to Cite

1.
Usychenko К. The using of genetic markers as a possibility of predicting the rate of progress of liver fibrosis in patients with chronic hepatitis B. Med. perspekt. [Internet]. 2023Sep.29 [cited 2024Nov.13];28(3):45-54. Available from: https://journals.uran.ua/index.php/2307-0404/article/view/288931

Issue

Vol. 28 No. 3 (2023)

Section

CLINICAL MEDICINE

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