Клиническое значение аллелей HLA DRB1*1101 и HLA-DQB1*03 при гепатит С- вирусной инфекции

В .М. Мицура, Е.В. Воропаев, С.В. Жаворонок, О.В. Осипкина, О.Ю.Баранов

2013 №3 | Клинический обзор

Аннотация

Список литературы

При инфекции, вызванной вирусом гепатита С, важное значение имеет клеточный иммунный ответ, эффективность которого зависит от человеческих лейкоцитарных антигенов (HLA молекул). Имеются сведения, что аллели HLA-DRB1*1101 и HLA-DQB1*03 могут обладать «защитным» действием от заражения ВГС и хронизации, приводить к раннему клиренсу инфекции, замедлять прогрессирование фиброза печени, увеличивать вероятность ответа на противовирусную терапию. Нами изучено носительство данных аллелей у 103 пациентов с хроническим гепатитом С (ХГС), их частота не отличается от контрольной группы. Установлено, что аллель HLA-DQB1*03 ассоциировался с меньшей выраженностью фиброза печени. Аллели HLA DRB1*1101 и HLA-DQB1*03 не оказывают влияния на эффективность лечения ХГС и не связаны с генотипом интерлейкина-28В.

Ключевые слова:

хронический гепатит С, аллели HLA DRB1*1101 и HLA-DQB1*03, прогрессирование фиброза печени, эффективность лечения

Clinical value of HLA DRB1*1101 and HLA-DQB1*03 alleles in hepatitis C virus-infection

The cellular immune response in hepatitis C-virus (HCV) infection is very important, its effectiveness depends on human leukocyte antigens (HLA) molecules. It is known that HLA-DRB1*1101 and HLA-DQB1*03 alleles may “protect” from HCV infection and its chronization, lead to early viral clearance, slow down liver fibrosis progression and increase the possibility of antiviral therapy response. The carriage of these alleles was studied in 103 patients with chronic hepatitis C (CHC). Frequency of alleles did not differ from control group. It was found that HLA-DQB1*03 allele was associated with less extent of liver fibrosis. HLA-DRB1*1101 and HLA-DQB1*03 alleles had no impact on treatment effectiveness and were not connected with interleukin-28B genotypes.

Keywords

chronic hepatitis C, HLA-DRB1*1101 and HLA-DQB1*03 alleles, liver fibrosis progression, treatment effectiveness

1. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C / C.-T. Wai [et al.] // Hepatology. – 2003. –Vol. 38. – P.518-526.
2. Association between MHC class II alleles and clearance of circulating hepatitis C virus. Members of the Trent Hepatitis C Virus Study Group / E.J. Minton [et al.] // J. Infect. Dis. – 1998. – Vol.178. – P.39–44.
3. Barrett, S. Association of the HLA-DRB1*01 allele with spontaneous viral clearance in an Irish cohort infected with hepatitis C virus via contaminated anti-D immunoglobulin / S. Barrett, E. Ryan, J. Crowe // J. Hepatol. – 1999. – Vol.30, N6. – P.979-983.
4. Bedossa, P. Assessment of hepatitis C: non-invasive ﬁbrosis markers and/or liver biopsy /P.Bedossa // Liver Int. – 2009. – Vol. 29, Suppl. 1. – P. 19–22.
5. Clustering of poor prognostic factors in patients with chronic hepatitis С /M. Swain [еt al.] // J. Hepatol. – 2005. – N 42, Suppl. 2. – Р. 222.
6. Distribution of the human leukocyte antigen class II alleles in Brazilian patients with chronic hepatitis C virus infection / D.B.Corghi [et al.] // Braz. J. Med. Biol. Res. – 2008. – Vol.41. – P.884–889.
7. DNA polymorphisms and response to treatment in patients with chronic hepatitis C: results from the HALT-C trial / T.R.Morgan [et al.] // J. Hepatol. – 2008.– Vol. 49. – P. 548–556.
8. DRB1 alleles in relation to severity of liver disease in patients with chronic hepatitis C / W. Kryczka [et al.] // Med. Sci. Monit. – 2001. – Vol.7. – P.217–220.
9. Histological features and HLA class II alleles in hepatitis C virus chronically infected patients with persistently normal alanine aminotransferase levels / C. Renou [et al.] // Gut.– 2002.– Vol. 51. –P.585–590.
10. HLA association with hepatitis C virus infection / S.Vejbaesya [et al.] // Hum. Immunol. – 2000. –Vol.61. – P.348–353.
11. HLA class I allelic diversity and progression of ﬁbrosis in patients with chronic hepatitis C / K . Patel [et al.] // Hepatology. – 2006. – Vol. 43. – P. 241–249.
12. HLA Class II Alleles and Chronic Hepatitis C Virus Infection / L.O.F. Cangussu [et al.] // Scandinavian Journal of Immunolo gy. – Vol.74. – P. 282–287.
13. HLA class II genes determine the natural variance of hepatitis C viral load / L.J. Fanning [et al.] // Hepatology.–2001. – Vol.33. – P.224–230.
14. Host Genetic Factors and Antiviral Immune Respo nses to HCV / C.L. Thio // Clin. Liver Dis. – 2008. – Vol. 12, №3. –P. 713–726.
15. Human leukocyte antigen alleles and the response to pegylated interferon/ribavirin therapy in chronic hepatitis C patients / C.Y.Dai [et al.] // Antiviral Res. – 2010. – Vol.85, N2. – P.396-402.
16. Human leukocyte antigen class II and III alleles and severity of hepatitis C virus-related chronic liver disease / M. Asti [et al.] // Hepatology. – 1 999. – Vol. 29. – P.1272–1279.
17. Human leukocyte antigen class II associations with hepatitis C virus clearance and virus-speciﬁc CD4 T cell response among Ca ucasians and African Americans / R.A. Harris [et al.] // Hepatology. – 2008. – Vol.48. –P.70–79.
18. Human leukocyte antigen class II DQB1*0301, DRB1*1101 alleles and spontaneous clearance of hepatitis C virus infect ion: a meta-analysis / X.Hong [et al.] // World J. Gastroenterol.— 2005.— Vol. 11, N 46.— P. 7302—7307.
19. IL28B CC-genotype association with HLA-DQB1*0301 allele increases the prediction of spontaneous HCV RNA clearance in thalassaemic HCV-infected patients / A. Mangia [et al.] // Antivir. Ther. – 2011. – Vol. 16, N8. – P.1309-1316.
20. Importance of host genet ic factors HLA and IL28B as predictors of response to pegylated interferon and ribavirin /P.M. de Rueda [et al.] // Am. J. Gastroenterol. – 2011. – Vol. 106, N7. –P. 1246-1254.
21. Influence of HLA alleles in response to treatment with pegylated interferon-alpha and ribavirin in patients with chronic hepatitis C / A.V. Marangon [et al.] // Int. J. Immunogenet. – 2012. – Vol.39, N4. –P.296-302.
22. Inﬂuence of MHC class II genotype on outcome of infection with hepatitis C virus. The HENCORE group. Hepatitis C Europ ean Network for Cooperative Research / M. Thursz [et al.] // Lancet.–1999. – Vol.354.– P.2119–2124.
23. Lavanchy, D. Global burden of hepatitis C // Liver Int. – 2009. – Vol. 29, Suppl.l. – P.74-81.
24. Low frequency of HLA-DRB1*11 in hepatitis C virus induced end stage liver disease / H.L.Tillmann [et al.] // Gu t. – 2001. – Vol.48. – P.714–718.
25. Patient HLA-DRB1* and DQB1* allele and haplotype association with hepatitis C virus persistence and clearance / L.Ali [et al.] // J. Gen. Virol. – 2010. –Vol. 91. – P.1931–1938.
26. Response to interferon therapy: influence of human leucocyte antigen alleles in patients with chronic hepatitis C / H. Sim [et al.] // J. Viral Hepatit. – 1998. – Vol. 5. – P.249-253.
27. Role of the specific T-cell response for clearance and control of hepatitis C virus / G.R.Pape [et al.] // J. Viral Hepat. – 19 99.– Vol.6, Suppl. 1. –P.36-40
28. Selection-Driven Immune Escape Is Not a Significant Factor in the Failure of CD4 T Cell Responses in Persistent Hepatitis C Virus Infection / M.J. Fuller [et al.] // Hepatology. – 2010. – Vol. 51, N 2. – P. 378–387.
29. The association between the genetic polymorphism of HLA-DQA1, DQB1, and DRB1 and serum alanine aminotransferase levels in chronic hepatitis C in the Chinese population / R.B. Yu [et al.] // J. Gastroenterol. H epatol. –2008. – Vol.23, N9. – P.1394-1402.
30. Tillmann, H.L. Hepatitis C /H.L. Tillmann, J.G. McHutchison // Zakim and Boyer’s hepatology: a textbook of liver disease / Ed. by T.D. Boyer, M.P. Manns, A.J. Sanyal.— Elsevier, Sanders. –6 th ed., 2012. – P.564-598.
31. Yenigun, A. Decreased frequency of the HLA- DRB1*11 allele in patients with chronic hepatitis C virus infection / A.Yenigun, B.Durupinar // J. Virol. – 2002. – Vol.76. – P.1787–178 9.