1887

Abstract

Low-level hepatitis C virus (HCV) RNA may persist in PBMCs after successful treatment of chronic hepatitis C, but the consequences of this phenomenon are unclear. Forty-nine patients who achieved a sustained virological response (SVR) after pegylated IFN and ribavirin therapy were analysed 52–66 months after the SVR. HCV RNA was detected in PBMCs from 18 patients (47.4 %), and PBMCs in two patients stained positive for non-structural protein 3 (NS3). Quantification of various cytokine and chemokine transcripts in PBMCs revealed that levels of IL-6, IL-8, IL-12, TNF-α and macrophage inflammatory protein 1β were significantly higher in HCV-positive patients than in HCV-negative individuals. In conclusion, persistence of HCV RNA in PBMCs of patients with a SVR appears to be associated with immune activation.

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2014-09-01
2024-03-28
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References

  1. Akdis M., Burgler S., Crameri R., Eiwegger T., Fujita H., Gomez E., Klunker S., Meyer N., O’Mahony L. other authors 2011; Interleukins, from 1 to 37, and interferon-γ: receptors, functions, and roles in diseases. J Allergy Clin Immunol 127:701–721 [View Article][PubMed]
    [Google Scholar]
  2. Benjamini Y., Hochberg Y. 1995; Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc 57:289–300
    [Google Scholar]
  3. Fujiwara K., Allison R. D., Wang R. Y., Bare P., Matsuura K., Schechterly C., Murthy K., Marincola F. M., Alter H. J. 2013; Investigation of residual hepatitis C virus in presumed recovered subjects. Hepatology 57:483–491 [View Article][PubMed]
    [Google Scholar]
  4. Ghany M. G., Nelson D. R., Strader D. B., Thomas D. L., Seeff L. B. American Association for Study of Liver Diseases 2011; 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 54:1433–1444 [View Article][PubMed]
    [Google Scholar]
  5. Haller O., Frese M., Kochs G. 1998; Mx proteins: mediators of innate resistance to RNA viruses. Rev Sci Tech 17:220–230[PubMed]
    [Google Scholar]
  6. Jacobson I. M., Cacoub P., Dal Maso L., Harrison S. A., Younossi Z. M. 2010; Manifestations of chronic hepatitis C virus infection beyond the liver. Clin Gastroenterol Hepatol 8:1017–1029 [View Article][PubMed]
    [Google Scholar]
  7. Jimenez-Sousa M. A., Almansa R., de la Fuente C., Caro-Paton A., Ruiz L., Sanchez-Antolín G., Gonzalez J. M., Aller R., Alcaide N. other authors 2010; Increased Th1, Th17 and pro-fibrotic responses in hepatitis C-infected patients are down-regulated after 12 weeks of treatment with pegylated interferon plus ribavirin. Eur Cytokine Netw 21:84–91[PubMed]
    [Google Scholar]
  8. Kisiel E., Radkowski M., Pawelczyk A., Horban A., Stanczak J., Bukowska-Ośko I., Caraballo Cortes K., Kaźmierczak J., Popiel M., Laskus T. 2014; Seronegative hepatitis C virus infection in patients with lymphoproliferative disorders. J Viral Hepat 21:424–429 [View Article][PubMed]
    [Google Scholar]
  9. Laskus T., Radkowski M., Wang L. F., Nowicki M., Rakela J. 2000; Uneven distribution of hepatitis C virus quasispecies in tissues from subjects with end-stage liver disease: confounding effect of viral adsorption and mounting evidence for the presence of low-level extrahepatic replication. J Virol 74:1014–1017 [View Article][PubMed]
    [Google Scholar]
  10. Livak K. J., Schmittgen T. D. 2001; Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods 25402–408 [CrossRef]
    [Google Scholar]
  11. Machida K., Cheng K. T., Sung V. M., Levine A. M., Foung S., Lai M. M. 2006; Hepatitis C virus induces toll-like receptor 4 expression, leading to enhanced production of beta interferon and interleukin-6. J Virol 80:866–874 [View Article][PubMed]
    [Google Scholar]
  12. Moser B., Loetscher P. 2001; Lymphocyte traffic control by chemokines. Nat Immunol 2:123–128 [View Article][PubMed]
    [Google Scholar]
  13. Pearlman B. L., Traub N. 2011; Sustained virologic response to antiviral therapy for chronic hepatitis C virus infection: a cure and so much more. Clin Infect Dis 52:889–900 [View Article][PubMed]
    [Google Scholar]
  14. Pham T. N., MacParland S. A., Mulrooney P. M., Cooksley H., Naoumov N. V., Michalak T. I. 2004; Hepatitis C virus persistence after spontaneous or treatment-induced resolution of hepatitis C. J Virol 78:5867–5874 [View Article][PubMed]
    [Google Scholar]
  15. Pham T. N., Mercer S. E., Michalak T. I. 2009; Chronic hepatitis C and persistent occult hepatitis C virus infection are characterized by distinct immune cell cytokine expression profiles. J Viral Hepat 16:547–556 [View Article][PubMed]
    [Google Scholar]
  16. Quiroga J. A., Martín J., Navas S., Carreño V. 1998; Induction of interleukin-12 production in chronic hepatitis C virus infection correlates with the hepatocellular damage. J Infect Dis 178:247–251 [View Article][PubMed]
    [Google Scholar]
  17. Radkowski M., Gallegos-Orozco J. F., Jablonska J., Colby T. V., Walewska-Zielecka B., Kubicka J., Wilkinson J., Adair D., Rakela J., Laskus T. 2005; Persistence of hepatitis C virus in patients successfully treated for chronic hepatitis C. Hepatology 41106–114 [CrossRef]
    [Google Scholar]
  18. Saleh M. G., Tibbs C. J., Koskinas J., Pereira L. M., Bomford A. B., Portmann B. C., McFarlane I. G., Williams R. 1994; Hepatic and extrahepatic hepatitis C virus replication in relation to response to interferon therapy. Hepatology 20:1399–1404 [View Article][PubMed]
    [Google Scholar]
  19. Viganò S., Perreau M., Pantaleo G., Harari A. 2012; Positive and negative regulation of cellular immune responses in physiologic conditions and diseases. Clin Dev Immunol 2012:485781 [View Article][PubMed]
    [Google Scholar]
  20. Wilkinson J., Radkowski M., Eschbacher J. M., Laskus T. 2010; Activation of brain macrophages/microglia cells in hepatitis C infection. Gut 59:1394–1400 [View Article][PubMed]
    [Google Scholar]
  21. Zignego A. L., Giannini C., Gragnani L. 2012; HCV and lymphoproliferation. Clin Dev Immunol 2012:980942 [View Article][PubMed]
    [Google Scholar]
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