Immune system and damages of liver at chronic hepatites B and C
Abstract
The aim of review. To present modern data on a role of adaptive immunodefence in development of chronic viral damage of liver and mechanisms of influence of hepatitis viruses B and C (HBV and HCV) on functional activity of cytotoxic lymphocytes (CTL).
Original positions. There are some mechanisms of HBV and HCV suppressing effect on immune response parts: exhaustion of virus-specific CTL functional activity as a result of persistence of high concentrations of viral antigens; elevation of activity of regulatory Т-cells; ability HBV to exist in the form of sustained endocellular template – covalently closed circular DNA (ccc DNA); mutations of genome HCV, allowing «to escape» from immune supervision; direct operation action of HCV proteins on Т-cells. The role of activated platelets in immunopathological reactions is also considered at chronic viral liver damage.
Conclusion. Application at chronic hepatitis B and C of up-to-date algorithms of antiviral therapy including agents like interferon, ribavirin and nucleotides/nucleosides analogues, does not allow to achieve at significant part of patients long-lasting suppression of viral replication that can result in persistence of replication HBV or HCV, activations of inflammatory and necrotic processes in the liver, clinically manifesting as relapse of hepatitis with subsequent development of liver cirrhosis and hepatocellular carcinoma. Evaluation of efficacy of antiviral therapy with the help of dynamic assessment of viral load and other viral markers yields only indirect representation of activity of pathological process. The recent scientific development offer idea of monitoring of parameters of innate (congenital) and adaptive (acquired) immunodefence at patients with chronic viral hepatites at antiviral treatment, and development of drugs, capable to sustain quantitative and functional stability of virus-specific Т-cells.
References
1. Ивашкин В.Т. Механизмы иммунной толерантности и патологии печени // Рос. журн. гастроэнтерол. гепатол. колопроктол. – 2009. – Т. 19, № 2. – С. 8–13.
2. Ивашкин В.Т. Основные понятия и положения фундаментальной иммунологии // Рос. журн. гастроэнтерол. гепатол. колопроктол. – 2008. – Т. 18, № 4. – С.
3. Bartenschlager R. New insights the hepatitis C virus replication cycle. Monothematic conference: Immune Mediated Liver Injury. – Hamburg, Germany, December 4–6, 2008.
4. Bertoletti A. Immune pathogenesis of HBV. Monothematic conference: Immune Mediated Liver Injury. – Hamburg, Germany, December 4–6, 2008.
5. Boni С., Fiscaro P., Valdatta C. et al. Characterization of hepatitis B virus (HBV) – specific T-cell dysfunction of chronic HBV infection // J. Virol. – 2007. – Vol. 81. – P. 4215–4225.
6. Dunn C., Brunetto M., Reynolds G. et al. Cytokines induced during chronic hepatitis B virus infection promote a pathway for NK all-mediated liver damage // J. Exp. Med. – 2007. – Vol. 204. – P. 667–680.
7. Iannacone M., Sitia G., Guidotti L. Platelets promote liver injury induced by virus-specific CTL. Monothematic conference: Immune Mediated Liver Injury. Hamburg, Germany, December 4–6, 2008.
8. Klenerman Р.T. Cell responses in persistent virus infection. Monothematic conference: Immune Mediated Liver Injury. – Hamburg, Germany, December 4–6, 2008.
9. Lang K.S., Georgiev P., Recher M. et al. Immunoprivileged status of the liver is controlled by Toll-like receptor 3 signalling // J. Clin. Invest. – 2006. – Vol. 116. – P. 2456–2463.
10. Lopes A.R., Kellam P., Das A. et al. Bim-mediated deletion of antigen-specific CD8 T cells in patients unable to control HBV infection // J. Clin. Invest. – 2008. – Vol. 118. – P. 1835–1845.
11. Nakamoto N. et al. Functional restoration of HCV-specific CD8 T cells by PD-1 blockade is defined by PD-1 expression and compartmentalization // Gastroenterology. – 2008. – Vol. 134. – P. 1927–1937.
12. Protzer U. Virology of hepatitis B viruses. Monothematic conference: Immune Mediated Liver Injury. – Hamburg, Germany, December 4–6, 2008.
13. Rehermann B., Nascimbeni M. Immunology of hepatitis B and hepatitis C virus infection // Nat. Rev. Immunol. – 2005. – Vol. 5. – P. 215–229.
14. Saito T. et al. Regulation of innate immunity against hepatitis C virus infection // Hepatol. Res. – 2008. – Vol. 38. – P. 115–122.
15. Urbani S. et al. Outcome of acute hepatitis C is related to virus-specific CD4 function and maturation of antiviral memory CD8 responses // Hepatology. – 2006. – Vol. 44. – P. 126–139.
16. Wieland S.F. et al. Intrahepatic induction of alpha/beta interferon eliminates viral RNA-containing capsids in hepatitis B virus transgenic mice // J. Virol. – 2005. – Vol. 79. – P. 9369–9380.
Review
For citations:
Ivashkin V.T. Immune system and damages of liver at chronic hepatites B and C. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2009;19(6):4-10. (In Russ.)
Views:
23
Email this article 
