Hepatitis C virus Genotype 3: that "simple", yet that "complex"


Cite item

Full Text

Abstract

The data on natural course of chronic viral hepatitis C infection (HCV) and the efficacy of antiviral treatment depending on virus genotype are summarized in the article. The significance of virus genotype in progression of liver febrosis and liver steatosis is discussed. It is pointed out that chronic HCV infection caused by genotype 3 is characterized by a more aggressive clinical course of disease and less favorable prognosis. Optimal approaches to the management of patients with genotype 3 of chronic HCV infection as well as perspectives of antiviral therapy in this group of patients are discussed in the article.

Full Text

Вирус гепатита С 3-го генотипа: такой "простой", такой "сложный". - Аннотация. Представлены данные о естественном течении и эффективности терапии хронического гепатита С, вызванного вирусами различных генотипов. Обсуждается роль генотипа вируса в прогрессировании фиброза и формировании стеатоза печени. Отмечается, что хронический гепатит С, вызванный вирусом 3-го генотипа, характеризуется более агрессивным течением и менее благоприятным прогнозом. Определены оптимальные подходы к ведению больных хроническим гепатитом С, вызванного вирусом 3-го генотипа, а также перспективы противовирусной терапии у пациентов данной категории.
×

References

  1. Shepard C.W., Finelli L., Alter M.J. Global epidemiology of hepatitis C virus infection. Lancet Infect Dis 2005; 5: 558-567.
  2. Simmonds P., Bukh J., Combet C. et al. Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes. Hepatology 2005; 42 (4): 962-973.
  3. Lavanchy D. Evolving epidemiology of hepatitis C virus. Clin Microbiol Infect 2011; 17 (2): 107-115.
  4. Пименов Н.Н., Чуланов В.П., Комарова С.В. и др. Гепатит С в России: эпидемиологическая характеристика и пути совершенствования диагностики и надзора. Эпидемиол и инфекц бол 2012; 3: 4-10.
  5. Соринсон С.Н. Особенности патогенеза и течения гепатита С. Оптимальные сроки лечения интерфероном. Вирусные гепатиты: достижения и перспективы 1998; 1: 3-8.
  6. Poynard T., Bedossa P., Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. Lancet 1997; 349: 825-832.
  7. Seeff L.B. Natural history of hepatitis C. Am J Med 1999; 107: S10-S15.
  8. Deuffic-Burban S., Poynard T., Valleron A.J. Quantification of fibrosis progression in patients with chronic hepatitis C using a Markov model. J Viral Hepat 2002; 9: 114-122.
  9. Serfaty L., Poujol-Robert A., Carbonell N. et al. Effect of the interaction between steatosis and alcohol intake on liver fibrosis progression in chronic hepatitis C. Am J Gastroenterol 2002; 97: 1807-1812.
  10. Wiley T.E., McCarthy M., Breidi L., Layden T.J. Impact of alcohol on the histological and clinical progression of hepatitis C infection. Hepatology 1998; 28: 805-809.
  11. Nousbaum J.B., Pol S., Nalpas B. et al. Hepatitis C virus type 1b (II) infection in France and Italy. Collaborative Study Group. Ann Intern Med 1995; 122: 161-168.
  12. Silini E., Bono F., Cividini A. et al. Differential distribution of hepatitis C virus genotypes in patients with and without liver function abnormalities. Hepatology 1995; 21: 285-290.
  13. Zein N.N., Rakela J., Poterucha J.J. et al. Hepatitis C genotypes in liver transplant recipients: distribution and 1-year follow-up. Liver Transpl Surg 1995; 1 (6): 354-357.
  14. Féray C., Gigou M., Samuel D. et al. Influence of the genotypes of hepatitis C virus on the severity of recurrent liver disease after liver transplantation. Gastroenterology 1995; 108: 1314-1317.
  15. Castera L., Hezode C., Roudot-Thoraval F. et al. Worsening of steatosis is an independent factor of fibrosis progression in untreated patients with chronic hepatitis C and paired liver biopsies. Gut 2003; 52: 288-292.
  16. Czaja A.J., Carpenter H.A., Santrach P.J., Moore S.B. Host- and disease-specific factors affecting steatosis in chronic hepatitis C. J Hepatol 1998; 29: 198-206.
  17. Bochud P.Y., Cai T., Overbeck K. et al. Genotype 3 is associated with accelerated fibrosis progression in chronic hepatitis. J Hepatol 2009; 51 (4): 655-666.
  18. Westin J., Nordlinder H., Lagging M. et al. Steatosis accelerates fibrosis development over time in hepatitis C virus genotype 3 infected patients. J Hepatol 2002; 37: 837-842.
  19. Rubbia-Brandt L., Fabris P., Paganin S. et al. Steatosis affects chronic hepatitis C progression in a genotype specific way. Gut 2004; 53 (3): 406-412.
  20. De Nicola S., Aghemo A., Rumi M.G., Colombo M. HCV genotype 3: an independent predictor of fibrosis progression in chronic hepatitis C. J Hepatol 2009; 51 (5): 964-966.
  21. Fartoux L., Chazouillères O., Wendum D. et al. Impact of steatosis on progression of fibrosis in patients with mild hepatitis C. Hepatology 2005; 41 (1): 82-87.
  22. Kasprzak A., Zabel M., Biczysko W. et al. Expression of cytokines (TNF-α, IL-1α, and IL-2) in chronic hepatitis C: Comparative Hybridocytochemical and Immunocytochemical Study in children and adult patients. J Histochem Cytochem 2004; 52 (1): 29-38.
  23. Leandro G., Mangia A., Hui J. et al. Relationship between steatosis, inflammation, and fibrosis in chronic hepatitis C: a meta-analysis of individual patient data. Gastroenterology 2006; 130: 1636-1642.
  24. Cua I.H., Hui J.M., Kench J.G., George J. Genotype-specific interactions of insulin resistance, steatosis, and fibrosis in chronic hepatitis C. Hepatology 2008; 48 (3): 723-731.
  25. Younossi Z.M., McCullough A.J., Ong J.P. et al. Obesity and non-alcoholic fatty liver disease in chronic hepatitis C. J Clin Gastroenterol 2004; 38 (8): 705-709.
  26. Asselah T., Rubbia-Brandt L., Marcellin P., Negro F. Steatosis in chronic hepatitis C: why does it really matter? Gut 2006; 55 (1):123-130.
  27. Browning J.D., Szczepaniak L.S., Dobbins R. et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004; 40 (6):1387-1395.
  28. Nomura H., Kashiwagi S., Hayashi J. et al. Prevalence of fatty liver in a general population of Okinawa, Japan. Jpn J Med 1988; 27 (2): 142-149.
  29. Hwang S.J., Luo J.C., Chu C.W. et al. Hepatic steatosis in chronic hepatitis C virus infection: prevalence and clinical correlation. J. Gastroenterol Hepatol 2001; 16: 190-195.
  30. Tsutsumi T., Suzuki T., Shimoike T. et al. Interaction of hepatitis C virus core protein with retinoid X receptor a modulates its transcriptional activity. Hepatology 2002; 35: 937-946.
  31. Hourioux C., Patient R., Morin A. et al. The genotype 3-specific hepatitis C virus core protein residue phenylalanine 164 increases steatosis in an in vitro cellular model. Gut 2007; 56: 1302-1308.
  32. Perlemuter G., Sabile A., Letteron P. et al. 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: 185-194.
  33. Jackel-Cram C., Babiuk L.A., Liu Q.J. Up-regulation of fatty acid synthase promoter by hepatitis C virus core protein: genotype-3a core has a stronger effect than genotype-1b core. Hepatology 2007; 46 (6): 999-1008.
  34. Kim K.H., Hong S.P., Kim K. et al. HCV core protein induces hepatic lipid accumulation by activating SREBP1 and PPARc. Biochem Biophys Res Commun 2007; 355 (4): 883-888.
  35. Okuda M., Li K., Beard M.R. et al. Mitochondrial injury, oxidative stress, and antioxidant gene expression are induced by hepatitis C virus core protein. Gastroenterology 2002; 122: 366-375.
  36. Abid K., Pazienza V., De Gottardi A. et al. An in vitro model of hepatitis C virus genotype 3a-associated triglycerides accumulation. J Hepatol 2005; 42: 744-751.
  37. Grassi A., Ballardini G., Susca M. et al. HCV liver infection and liver steatosis: evidence for indirect mechanisms in genotype 3? Aliment Pharmacol Ther 2005; 22: 79-82.
  38. Asselah T., Boyer N., Marcellin P. Steatosis in hepatitis C: what does it mean? Gastroenterol Clin Biol 2003; 27 (12): 1073-1075.
  39. Fartoux L., Poujol-Robert A., Guechot J. et al. Insulin resistance is a cause of steatosis and fibrosis progression in chronic hepatitis C. Gut 2005; 54: 1003-1008.
  40. Adinolfi L.E., Gambardella M., Andreana A. et al. Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity. Hepatology 2001; 33: 1358-1364.
  41. Hui J.M., Kench J., Farrell G.C. et al. Genotype specific mechanisms for hepatic steatosis in chronic hepatitis C infection. J Gastroenterol Hepatol 2002; 17: 873-881.
  42. Hezode C., Roudot-Thoraval F., Zafrani E.S. et al. Different mechanisms of steatosis in hepatitis C virus genotypes 1 and 3 infections. J Viral Hepat 2004; 11: 455-458.
  43. Patton H.M., Patel K., Behling C. et al. The impact of steatosis on disease progression and early and sustained treatment response in chronic hepatitis C patients. J Hepatol 2004; 40: 484-490.
  44. Kumar D., Farrell G.C., Fung C., George G. Hepatitis C virus genotype 3 is cytopathic to hepatocytes: reversal of hepatic steatosis after sustained therapeutic response. Hepatology 2002; 36 (5): 1266-1272.
  45. Rubbia-Brandt L., Quadri R., Abid K. et al. Hepatocyte steatosis is a cytopathic effect of hepatitis C virus genotype 3. J Hepatol 2000; 33: 106-115.
  46. Barba G., Harper F., Harada T. et al. Hepatitis C virus core protein shows a cytoplasmic localization and associates to cellular lipid storage droplets. Proc. Natl Acad. Sci. USA 1997; 94: 1200-1205.
  47. Jhaveri R., McHutchison J., Patel K. et al. Specific polymorphisms in hepatitis C virus genotype 3 core protein associated with intracellular lipid accumulation. J Infect Dis 2008; 197: 283-291.
  48. Moriya K., Nakagawa K., Santa T. et al. Oxidative stress in the absence of inflammation in a mouse model for hepatitis C virus-associated hepatocarcinogenesis. Cancer Res 2001; 61: 4365-4370.
  49. Nkontchou G., Ziol M., Aout M. et al. HCV genotype 3 is associated with a higher hepatocellular carcinoma incidence in patients with ongoing viral C cirrhosis. J Viral Hepat 2011; 18: 516-522.
  50. Della Rossa A., Tavoni A., Baldini C., Bombardieri S. Mixed cryoglobulinemia and hepatitis C virus association: ten years later. Isr Med Assoc J 2001; 3 (6): 430-434.
  51. Ramos-Casals M., Forns X., Brito-Zerón P. et al. Cryoglobulinaemia associated with hepatitis C virus: influence of HCV genotypes, HCV-RNA viraemia and HIV coinfection. J Viral Hepat 2007; 14 (10): 736-742.
  52. Parise E.R., de Oliveira A.C., Ferraz M.L. et al. Cryoglobulinemia in chronic hepatitis C: clinical aspects and response to treatment with interferon alpha and ribavirin. Rev Inst Med Trop Sao Paulo 2007; 49 (2): 67-72.
  53. Vigani A.G., Pavan M.H., Tozzo R. et al. Comparative study of patients with chronic hepatitis C virus infection due to genotypes 1 and 3 referred for treatment in southeast Brazil. BMC Infect Dis 2008; 8: 164.
  54. Manns M.P., McHutchison J.G., Gordon S.C. et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001; 358 (9286): 958-965.
  55. Fried M.W., Shiffman M.L., Reddy K.R. et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002; 347 (13): 975-982.
  56. Andriulli A., Mangia A., Iacobellis A. et al. Meta-analysis: the outcome of anti-viral therapy in HCV genotype 2 and genotype 3 infected patients with chronic hepatitis. Aliment Pharmacol Ther 2008; 28 (4): 397-404.
  57. Shah S.R., Patel K., Marcellin P. et al. Steatosis is an independent predictor of relapse following rapid virologic response in patients with HCV genotype 3. Clin Gastroenterol Hepatol 2011; 9: 688-693.
  58. Hadziyannis S.J., Sette H. Jr., Morgan T.R. et al. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 2004; 140 (5): 346-355.
  59. EASL Clinical Practice Guidelines: Management of hepatitis C virus infection. J Hepatol 2011; 55: 245-264.
  60. Sarin S.K., Kumar C.K. Treatment of patients with genotype 3 chronic hepatitis C - current and future therapies. Liver Int 2012; 32 Suppl 1: 141-145.
  61. Ge D., Fellay J., Thompson A.J. et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 2009; 461 (7262): 399-401.
  62. Moghaddam A., Melum E., Reinton N. et al. IL28B genetic variation and treatment response in patients with hepatitis C virus genotype 3 infection. Hepatology 2011; 53: 746-754.
  63. Mangia A., Thompson A.J., Santoro R. et al. An IL28B polymorphism determines treatment response of hepatitis C virus genotype 2 or 3 patients who do not achieve a rapid virologic response. Gastroenterology 2010; 139 (3): 821-827.
  64. Ghany M.G., Nelson D.R., Strader D.B. et al. An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology 2011; 54: 1433-1444.
  65. Brainard D.M., Petry A., Van Dyck K. et al. Safety and antiviral activity of MK-5172, a novel HCV NS3/4a protease inhibitor with potent activity against known resistance mutants, in genotype 1 and 3 HCV-infected patients. Program and abstracts of the 61st Annual Meeting of the American Association for the Study of Liver Diseases; October 29 - November 2, 2010; Boston, Massachusetts. Abstract 807.
  66. Gane E.J., Rodriguez-Torres M., Nelson D.E. et al. Sustained virologic response (SVR) following RG7128 1500 mg BID/PEG-IFN/RBV for 28 days in HCV genotype 2/3 prior non-responders. Program and abstracts of the 45th Annual Meeting of the European Association for the Study of the Liver; April 14-18, 2010; Vienna, Austria. Abstract 37.
  67. Sulkowski M., Gardiner D., Lawitz E. et al. Potent viral suppression with all-oral combination of daclatasvir (NS5A inhibitor) and GS-7977 (NS5B inhibitor), ± ribavirin, in treatment-naive patients with chronic HCV GT1, 2, or 3. Program and abstracts of the 47th Annual Meeting of the European Association for the Study of the Liver; April 18-22, 2012; Barcelona, Spain. Abstract 1422.
  68. Ramos E.L. Preclinical and clinical development of pegylated interferon-lambda 1 in chronic hepatitis C. J Interferon Cytokine Res 2010; 30 (8): 591-595.
  69. Muir A.J., Shiffman M.L., Zaman A. et al. Phase 1b study of pegylated interferon lambda 1 with or without ribavirin in patients with chronic genotype 1 hepatitis C virus infection. Hepatology 2010; 52 (3): 822-832.
  70. Zeuzem S., Arora S., Bacon B. et al. Peginterferon lambda-1a (lambda) compared to peginterferon alfa-2a (alfa) in treatment-naive patients with HCV genotypes (G) 2 or 3: first SVR24 results from EMERGE phase IIB. Program and abstracts of the 47th Annual Meeting of the European Association for the Study of the Liver; April 18-22, 2012; Barcelona, Spain. Abstract 10.
  71. Flisiak R., Horban A., Gallay P. et al. The cyclophilin inhibitor Debio-025 shows potent anti-hepatitis C effect in patients coinfected with hepatitis C and human immunodeficiency virus. Hepatology 2008; 47: 817-826.
  72. Pawlotsky J.M., Sarin S.K., Foster G. et al. Alisporivir plus ribavirin is highly effective as interferon-free or interferon-add-on regimen in previously untreated HCV-GT2 or GT3 patients: SVR12 results from VITAL-1 phase 2b study. Program and abstracts of the 47th Annual Meeting of the European Association for the Study of the Liver; April 18-22, 2012; Barcelona, Spain. Abstract 1405.
  73. Flisiak R., Feinman S.V., Jablkowski M. et al. The cyclophilin inhibitor Debio 025 combined with PEG IFNalpha2a significantly reduces viral load in treatment-naive hepatitis C patients. Hepatology 2009; 49: 1460-1468.
  74. Pawlotsky J.M., Flisiak R., Rasenack J. et al. Once daily alisporivir interferon (IFN)-free regimens achieve high rates of early HCV clearance in previously untreated patients with HCV genotype (G) 2 or 3. Program and abstracts of the 62nd Annual Meeting of the American Association for the Study of Liver Diseases; November 4-8, 2011; San Francisco, California. Abstract LB-11.

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2012 Consilium Medicum

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
 

Address of the Editorial Office:

  • Novij Zykovskij proezd, 3, 40, Moscow, 125167

Correspondence address:

  • Alabyan Street, 13/1, Moscow, 127055, Russian Federation

Managing Editor:

  • Tel.: +7 (926) 905-41-26
  • E-mail: e.gorbacheva@ter-arkhiv.ru

 

© 2018-2021 "Consilium Medicum" Publishing house


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies