Preview

INVESTIGATION OF THE SIGNIFICANCE OF DETECTION OF THE NUCLEOCAPSID ANTIGEN OF THE HEPATITIS C VIRUS IN CHILDREN WITH CHRONIC HEPATITIS C

https://doi.org/10.22627/2072-8107-2017-16-4-17-21

Abstract

The aim of this study was to investigate the clinical and diagnostic significance of the detection of core-antigen of hepatitis C virus (HCV) in children with chronic hepatitis C (CHC). Sera of 101 patients and 24 non-infected participants were analyzed. Core-antigen was determined by chemiluminescent method using «ARCHITECT HCV Ag» (Abbott, USA). HCV RNA was detected by highly sensitive OT-PCA. The presence of liver fibrosis was established by non-invasive methods. Antibody to core-antigen was detected by ELISA using commercial test-systems. A correlation was found between concentration of core-antigen and HCV RNA, viral subtypes, ALT level, and presence of liver fibrosis. High sensitivity and specificity of the chemiluminescent method for the detection of core antigen in children with CHC was shown. For the first time three ranges of core-antigen concentrations were proposed. 

About the Authors

E. A. Leybman
National Research Centre of Epidemiology and Microbiology named after N.F. Gamaleya, Moscow
Russian Federation

PhD, junior researcher of laboratory of gene engineering products 

+7(499) 190-30-01



L. I. Nikolaeva
National Research Centre of Epidemiology and Microbiology named after N.F. Gamaleya, Moscow
Russian Federation
MD, leading researcher of laboratory of gene engineering products


G. V. Sapronov
National Research Centre of Epidemiology and Microbiology named after N.F. Gamaleya, Moscow; Russian Medical Academy of Continuing Professional Education, Moscow
Russian Federation
PhD, senior researcher of laboratory of gene engineering products


E. I. Samokhvalov
National Research Centre of Epidemiology and Microbiology named after N.F. Gamaleya, Moscow
Russian Federation
PhD, leading researcher of laboratory of viral ecology


O. B. Kovalev
Russian National Research Medical University named after N.I. Pirogov, Moscow
Russian Federation
MD, professor of the department of infectious diseases in children


V. A. Konev
Russian National Research Medical University named after N.I. Pirogov, Moscow
Russian Federation
PhD, assistant professor of the department of infectious diseases in children


V. F. Uchaikin
Russian National Research Medical University named after N.I. Pirogov, Moscow
Russian Federation
academician of RAS, MD, professor of the department of infectious diseases in children


References

1. Daw M.A., El-Bouzedi A.A., Ahmed M.O., Dau A.A., Agnan M.M., Drah A.M. Geographic integration of hepatitis C virus: A global threat. World J. Virol. 2016; 5(4):170—182.

2. Petruzziello A., Marigliano S., Loquercio G., Cozzolino A., Cacciapuoti C. Global epidemiology of hepatitis C virus infection: An up-date of the distribution and circulation of hepatitis C virus genotypes. World J. Gastroenterol. 2016; 22(34):7824—7840.

3. Пименов Н.Н., Чуланов В.П., Комарова С.В., Карандашова И.В., Неверов А.Д., Михайловская Г.В., Долгих В.А., Лебедева Е.Б., Пашкина К.В., Коршунова Г.С. Гепатит С в России: эпидемиологическая характеристика и пути совершенствования диагностики и надзора. Эпидемиология и инфекционные болезни. 2012; 17(3): 4—10. [Pimenov N.N., Chulanov V.P., Komarova S.V., Karandashova I.V., Neverov A.D., Mikhaylovskaya G.V., Dolgikh V.A., Lebedeva E.B., Pashkina K.V., Korshunova G.S. Hepatitis C in Russia: epidemiological characteristics and ways to improve diagnostics and surveillance. Epidemiologiya i Infectsionniy bolezni = Epidemiology and Infection Diseases. 2012; 17(3): 4—10. (In Russ)]

4. Mukomolov S., Trifonova G., Levakova I., Bolsun D., Krivanogova E. Hepatitis C in the Russian Federation: challenges and future directions. Hepat. Med. 2016; 8: 51—60.

5. Кистенёва Л.Б., Чешик С.Г., Самохвалов Е.И., Серобян А.Г., Малышев Н.А. Перинатальный гепатит С: комплексная оценка факторов риска. Российский вестник перинатологии и педиат- рии. 2012; 2: 58—63. [Kistenyova L.B., Cheshik S.G., Samokhvalov E.I., Serobyan A.G., Malyshev N.A. Perinatal hepatitis C: comprehensive assessment of risk factors. Possiyskiy Vestnik Perinatologii i Pediatrii = The Russian Herald of Perinatology and Pediatrics. 2012; 2: 58—63. (In Russ)]

6. Tanaka T., Lau J., Mizokami M., Orito E., Tanaka E., Kiyosawa K., Yasui K., Ohta Y., Hasegawa A., Tanaka S. Simple fluorescent enzyme immunoassay for detection and quantification of Hepatitis C viremia. J. Hepatol. 1995; 23(6): 742—745.

7. Aoyagi K., Ohue C., Iida K., Kimura T., Tanaka E., Kiyosawa K., Yagi S. Development of a simple and highly sensitive enzyme immunoassay for hepatitis C virus core antigen. J. Clin Microbiol. 1999; 37: 1802—1808.

8. Icardi G., Bruzzone B., Gota F., Torre F., Giannini E., Massone L., Li Bassi A., Lai P.L., Picciotto A, Ansaldi F. A new assay for hepatitis C virus (HCV) core antigen detection: an alternative to nucleic acid technologies in positive or indeterminate anti-HCV subjects? Ann. Ig. 2003; 15(6): 863—870.

9. Morota K., Fujinami R., Kinukawa H., Machida T., Ohno K., Saegusa H., Takeda K. A new sensitive and automated chemiluminescent microparticle immunoassay for quantitative determination of hepatitis C virus core antigen. J. Virol. Methods. 2009; 157(1): 8—14.

10. Ross R.S., Viazov S., Salloum S., Hilgard P., Gerken G., Roggendorf M. Analytical performance characteristics and clinical utility of a novel assay for total hepatitis C virus core antigen quantification. Clin. Microbiol. 2010; 48(4): 1161—1168.

11. Perlemuter G., Sabile A., Letteron P., Vona G., Topilco A., Chrétien Y., Koike K., Pessayre D., Chapman J., Barba G., Bréchot C. Hepatitis C virus core protein inhibits microsomal triglyceride transfer protein activity and very low density lipoprotein secretion: a model of viral-related steatosis. FASEB J. 2002;16(2): 185—194.

12. Korenaga M., Wang T., Li Y., Showalter L.A., Chan T., Sun J., Weinman S.A. Hepatitis C virus core protein inhibits mitochondrial electron transport and increases reactive oxygen species (ros) production. J. Biol. Chem. 2005; 280: 37481—37488.

13. Stone A.E., Mitchell A., Brownell J., Miklin D.J., Golden-Mason L., Polyak S.J., Gale M.J.Jr, Rosen H.R. Hepatitis C virus core protein inhibits interferon production by a human plasmacytoid dendritic cell line and dysregulates interferon regulatory factor-7 and signal transducer and activator of transcription (STAT) 1 protein expression. PLoS One. 2014; 9(5): 1—9.

14. Benzoubir N., Lejamtel C., Battaglia S., Testoni B., Benassi B., Gondeau C., Perrin-Cocon L., Desterke C., Thiers V., Samuel D., Levrero M., Bréchot C., Bourgeade M.F. HCV core-mediated activation of latent TGF- via thrombospondin drives the crosstalk between hepatocytes and stromal environment. J. Hepatol. 2013; 59(6): 1160—1168.

15. Yamanaka T., Kodama T., Doi T. Subcellular localization of HCV core protein regulates its ability for p53 activation and p21 suppression. Biochem. Biophys. Res. Commun. 2002; 294(3): 528— 534.

16. Park Y., Lee J.H., Kim B.S., Kim D.Y., Han K.H., Kim H.S. New automated hepatitis C virus (HCV) core antigen assay as an alternative to Real-Time PCR for HCV RNA quantification. J. Clin. Microbiol. 2010; 48(6): 2253—2256.

17. Tedder R.S., Tuke P., Wallis N., Wright M., Nicholson L., Grant P.R. Therapy-induced clearance of HCV core antigen from plasmapredicts an end of treatment viral response. J. Viral Hepatitis. 2013; 20: 65—71.

18. Ergünay K., Sener B., Alp A., Karakaya J., Hasçelik G. Utility of a commercial quantitative hepatitis C virus core antigen assay in a diagnostic laboratory setting. Diagn Microbiol Infect Dis. 2011; 70(4): 486—491.

19. Wang L., Lv H., Zhang G. Hepatitis C virus core antigen assay: an alternative method for hepatitis C diagnosis. Ann. Clin. Biochem. 2017; 54(2): 79—85.

20. Hadziyannis E., Minopetrou M., Georgiou A., Spanou F., Koskinas J. Is HCV core antigen a reliable marker of viral load? An evaluation of HCV core antigen automated immunoassay. Ann. Gastroenterol. 2013; 26(2): 146—149.

21. Bouvier-Alias M., Patel K., Dahari H., Beaucourt S., Larderie P., Blatt L., Hezode C., Picchio G., Dhumeaux D., Neumann A.U., McHutchison J.G., Pawlotsky J.M. Clinical utility of total HCV core antigen quantification: a new indirect marker of HCV replication. Hepatology. 2002; 36(1): 211—218.

22. Murayama A.A., Sugiyama N., Watashi K., Masaki T., Suzuki R., Aizaki H., Mizuochi T., Wakita T., Kato T. Japanese reference panel of blood specimens for evaluation of hepatitis C virus RNA and core antigen quantitative assays. Clin. Microbiol. 2012; 50(6): 1943— 1949.

23. Nguyen L.T., Dunford L., Freitas I., Holder P., Nguyen L.A., O'Gorman J., Connell J., Carr M., Hall W., De Gascun C. Hepatitis C virus core mutations associated with false-negative serological results for genotype 3a core antigen. J. Clin. Microbiol. 2015; 53(8): 2697— 2700.

24. Budkowska A., Kakkanas A., Nerrienet E., Kalinina O., Maillard P., Horm S.V., Dalagiorgou G., Vassilaki N., Georgopoulou U., Martinot M., Sall A.A., Mavromara P. Asynonymous mutations in the core gene are linked to unusual serological profile in hepatitis C virus infection. Plos One. 2011; 6(I1); e15871.

25. Nikolaeva L.I., Leybman E.A., Samokhvalov E.I., Kyuregyan K.K., Isaeva O.V., Kichatova V.K., Mikhailov M.I. Hepatitis C virus isolate Chu_1a core protein gene, partial cds. GenBank. 2014; KM05444515.

26. Nikolaeva L.I., Leybman E.A., Samokhvalov E.I., Kyuregyan K.K., Isaeva O.V., Kichatova V.K., Mikhailov M.I. Hepatitis C virus isolate Kul_2k/1b core protein gene, partial cds. GenBank. 2014; KM05444516.

27. Iijima A., Tanaka E., Kobayashi M., Yagi S., Mizokami M., Kiyosawa K. Relationship between histological prognosis of chronic hepatitis C and amount of hepatitis C virus core protein in serum. J. Gastroenterol. Hepatol. 2000; 15: 311—319.

28. Durante-Mangoni Е., Vallefuoco L., Sorrentino R., Iossa D., Perna E., Molaro R., Braschi U., Zampino R., Sodano G., Adinolfi L.E., Utili R., Portella G. Clinico-pathological significance of hepatitis C virus core antigen levels in chronic infection. J. Med. Virol. 2013; 85:1 913—1918.

29. Масолова О.В. Вирусный гепатит С: новые подходы к изучению патогенеза и разработка средств диагностики и профилактики. Автореф. дис. … дбн. М., 2011: 46. [Masolova O.V. Viral hepatitis C: new approaches to the study of pathogenesis and the development of diagnostic tools and prevention: Abstract of MD Thesis (Biol.). M, 2011: 46. (In Russ)].

30. Easterbrook P.J. Who to test and how to test for chronic hepatitis C infection. J. Hepatol. 2016; 65(1 Suppl): 46—66.

31. EASL (European Association for Study of Liver). Recommendations on Treatment of Hepatitis C — 2016. J. Hepatol. 2017; 66: 153—194.


Review

For citations:


Leybman E.A., Nikolaeva L.I., Sapronov G.V., Samokhvalov E.I., Kovalev O.B., Konev V.A., Uchaikin V.F. INVESTIGATION OF THE SIGNIFICANCE OF DETECTION OF THE NUCLEOCAPSID ANTIGEN OF THE HEPATITIS C VIRUS IN CHILDREN WITH CHRONIC HEPATITIS C. CHILDREN INFECTIONS. 2017;16(4):17-21. (In Russ.) https://doi.org/10.22627/2072-8107-2017-16-4-17-21

Views: 828


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2072-8107 (Print)
ISSN 2618-8139 (Online)