Sizova L. М.

ANALYSIS OF PREDICTORS OF THE EFFECTIVENESS OF ANTIVIRAL THERAPY FOR CHRONIC HEPATITIS C

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About the author:	Sizova L. М.
Heading	CLINICAL MEDICINE
Type of article	Scentific article
Annotation	The aim of the study was to determine the clinical and genetic predictors of the effectiveness of the dual antiviral therapy of chronic hepatitis C with pegylated interferons and ribavirin. The study was carried out to achieve the goal, which included 123 patients who have completed a course of antiviral therapy for chronic hepatitis C with pegylated interferon and ribavirin and the 24-week observation period. Among them, men ‒ 76 (61.8%), women ‒ 47 (38.2%), age from 20 to 63 years, the average ‒ 40.91±0.87. Depending on the effectiveness of treatment, patients were divided into those who have achieved ‒ 74 (60.2%) and did not reach ‒ 49 (39.8%) sustained virological response. As potential predictors of the effectiveness of antiviral therapy with pegylated interferons and ribavirin, 39 variables were examined and evaluated before it began, which included general clinical indices and genetic markers (the «mutant» alleles 299Gly of the TLR4 gene and 11Leu of the TLR7 gene). For each of them, a simple logistic regression analysis was carried out. The study refined and extended ideas about the predictors of low effectiveness of this regimen: confirmed recognized – 1 genotype HCV (ОR=0.16 [95% CI 0.06-0.41], р=0.000), over 40 years of age (ОR=0.38 [95% CI 0.18-0.80], р=0.012), the stage of liver fibrosis F3-F4 by METAVIR scale (ОR=0.27 [95% CI 0.12-0.59], р=0.001) and identified additional – leukopenia (ОR=0.22 [95% CI 0.07-0.62], р=0.004), levels of gamma-glutamyltranspeptidase and alkaline phosphatase above the upper limit of the norm (ОR=0.28 [95% CI 0.13-0.61], р=0.001 and ОR=0.02 [95% CI 0.001-0.50], р=0.015 respectively), the rapid rate of liver fibrosis progression (ОR=0.34 [95% CI 0.16-0.72], р=0.005) and the «mutant» 299Gly allele of the TLR4 gene (ОR=0.32 [95% CI 0.11-0.88], р=0.029). Relative to a variable such as obesity, there is a trend towards the reliability of associations (ОR=0.41 [95% СΙ 0.15-1.13], р=0.086). In the course of the individual comparative analysis, it was established that in the presence of these predictors of low effectiveness in patients with chronic hepatitis C, the frequency of achieving a sustained virological response for antiviral therapy of chronic hepatitis C with pegylated interferons and ribavirin is significantly lower than in their absence and is less than 50%. This fact points to the inadvisability of prescribing for these patients a dual antiviral therapy for chronic hepatitis C.
Tags	chronic hepatitis C, genes, predictors, antiviral therapy
Bibliography	Golubovskaya O. A. Nereshennyie problemyi i novyie gorizontyi v lechenii hronicheskogo gepatita S / O. A. Golubovskaya // GepatologIya. – 2015. – No. 4. – S. 6-14. Dubynska H. M. Vplyv polimorfizmu heniv TLR4 ta TLR7 na efektyvnist protyvirusnoi terapii khronichnoho hepatytu S / H. M. Dubynska, L. M. Syzova, T. I. Koval [ta in.] // Hepatolohiia. 2016. No.2 (32) S. 48-54. Zaytsev I. A. Prognozirovanie rezultatov protivovirusnoy terapii bolnyih hronicheskim virusnyim gepatitom S / I. A. Zaytsev // GepatologIya. – 2013. –N 2. – S. 4-13. Rekomendatsii po diagnostike i vedeniyu vzroslyih bolnyih gepatitom S // RZhGGK. – 2013. – T. 23. No. 2. – S. 41-70. Unifikovanyi klinichnyi protokol pervynnoi, vtorynnoi (spetsializovanoi), tretynnoi (vysokospetsializovanoi) medychnoi dopomohy. «Virusnyi hepatyt S u doroslykh» (Nakaz MOZ Ukrainy №729 vid 18.07.2016) Fedorchenko S. V. Hronicheskaya HCV-infektsiya: monografiya / S. V. Fedorchenko // – K.: Meditsina, - 2010. – 272 s. EASL Clinical Practice Guidelines: Management of hepatitis C virus infection // Journal of hepatology. – 2013. – Vol. 60. – Р. 392-420. EASL Recommendations on Treatment of Hepatitis C 2016 // Journal of hepatology. – 2017. – Vol. 66. – Р. 153-194. Emonts M. Polymorphisms in immune response genes in infectious diseases and autoimmune diseases / М. Emonts // – Erasmus University Rotterdam, - 2008. – 372 p. Howell J. Toll-like receptors in hepatitis C infection: implications for pathogenesis and treatment // J. Howell, P. Angus, P. Gow [et al.] // Journal of Gastroenterology and Hepatology. – 2013. – Vol. 28 (5). – Р. 766-776. Kawai Т. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity / T. Kawai, S. Akira // Immunity. – 2011. – Vol. 34. – № 5. – Р. 637-650. Periс M. Polymorphisms of Toll-like receptors 2 and 4 in chronically infected hepatitis C patients from north-east Croatia / M. Periс, Z. Bosnjak, B. Sarkanj [et al.] // Archives of virology. – 2015. – Vol. 160 (1). – Р. 297-304. Schott Е. Association of TLR7 single nucleotide polymorphisms with chronic HCV-infection and response to interferon-a-based therapy / Е. Schott, Н. Witt, К. Neumann [et al.] // Journal of viral hepatitis. – 2008. – Vol. 15 (1). – P. 71-78. Taghavi S. A. Relation between C.32 A>T polymorphism in TLR7 and response to treatment in chronic HCV-infection / S. A. Taghavi, H. Damangir, E. Kamali Sarvestani [et al.] // Armaghan Danesh. – 2009. – Vol. 14 (2). – Р. 105-116.
Publication of the article	«World of Medicine and Biology» №3(61), 2017 year, 063-067 pages, index UDK 16.36-002-085.281.8-037
DOI	10.26724/2079-8334-2017-3-61-63-67