Digestive Diseases and Sciences

, Volume 53, Issue 9, pp 2564–2568 | Cite as

Persistence of Hepatitis C Virus in Peripheral Blood Mononuclear Cells of Sustained Viral Responders to Pegylated Interferon and Ribavirin Therapy

  • Juan F. Gallegos-Orozco
  • Jorge Rakela
  • Marianne J. Rosati
  • Hugo E. Vargas
  • Vijayan Balan
Original Article


The aim of this paper was to assess the persistence of hepatitis C virus (HCV) among patients successfully treated with peginterferon and ribavirin. The persistence of viral RNA was evaluated in the serum and peripheral blood mononuclear cells (PBMCs) of 25 chronic hepatitis C patients with sustained viral response to peginterferon and ribavirin treatment up to 56 months after the completion of therapy. Viral RNA was detected in the peripheral blood mononuclear cell cultures of five patients (20%), but none had detectable serum HCV RNA. At present, the clinical relevance of this finding is unclear. It is possible that viral persistence and, specifically, the presence of HCV RNA in PBMCs may lead to HCV reactivation under special circumstances, such as immunosuppression.


Viral hepatitis Hepatitis C virus Viral persistence Peripheral blood mononuclear cells Peginterferon 



This work was supported in part by a grant from the Palumbo Foundation, the Edson Foundation and Roche Laboratories. The study sponsors did not participate in the design of the study, collection, analysis, or interpretation of the data, and were not involved in the writing of the manuscript.


  1. 1.
    Alter MJ, Kruszon-Moran D, Nainan OV, McQuillan GM, Gao F, Moyer LA et al (1999) The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. N Engl J Med 341(8):556–562. doi: 10.1056/NEJM199908193410802 PubMedCrossRefGoogle Scholar
  2. 2.
    Yan FM, Chen AS, Hao F, Zhao XP, Gu CH, Zhao LB et al (2000) Hepatitis C virus may infect extrahepatic tissues in patients with hepatitis C. World J Gastroenterol 6(6):805–811PubMedGoogle Scholar
  3. 3.
    Vargas HE, Laskus T, Radkowski M, Wilkinson J, Balan V, Douglas DD et al (2002) Detection of hepatitis C virus sequences in brain tissue obtained in recurrent hepatitis C after liver transplantation. Liver Transpl 8(11):1014–1019. doi: 10.1053/jlts.2002.36393 PubMedCrossRefGoogle Scholar
  4. 4.
    Sugiyama K, Kato N, Ikeda M, Mizutani T, Shimotohno K, Kato T et al (1997) Hepatitis C virus in pelvic lymph nodes and female reproductive organs. Jpn J Cancer Res 88(10):925–927PubMedGoogle Scholar
  5. 5.
    Qian C, Camps J, Maluenda MD, Civeira MP, Prieto J (1992) Replication of hepatitis C virus in peripheral blood mononuclear cells. Effect of alpha-interferon therapy. J Hepatol 16(3):380–383. doi: 10.1016/S0168-8278(05)80674-9 PubMedCrossRefGoogle Scholar
  6. 6.
    Willems M, Peerlinck K, Moshage H, Deleu I, Van den Eynde C, Vermylen J et al (1994) Hepatitis C virus-RNAs in plasma and in peripheral blood mononuclear cells of hemophiliacs with chronic hepatitis C: evidence for viral replication in peripheral blood mononuclear cells. J Med Virol 42(3):272–278. doi: 10.1002/jmv.1890420314 PubMedCrossRefGoogle Scholar
  7. 7.
    Okuda M, Hino K, Korenaga M, Yamaguchi Y, Katoh Y, Okita K (1999) Differences in hypervariable region 1 quasispecies of hepatitis C virus in human serum, peripheral blood mononuclear cells, and liver. Hepatology 29(1):217–222. doi: 10.1002/hep.510290117 PubMedCrossRefGoogle Scholar
  8. 8.
    Castillo I, Rodríguez-Iñigo E, Bartolome J, de Lucas S, Ortíz-Movilla N, López-Alcorocho JM et al (2005) Hepatitis C virus replicates in peripheral blood mononuclear cells of patients with occult hepatitis C virus infection. Gut 54(5):682–685. doi: 10.1136/gut.2004.057281 PubMedCrossRefGoogle Scholar
  9. 9.
    Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R et al (2001) Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 358(9286):958–965. doi: 10.1016/S0140-6736(01)06102-5 PubMedCrossRefGoogle Scholar
  10. 10.
    Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Gonçales FL Jr et al (2002) Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 347(13):975–982. doi: 10.1056/NEJMoa020047 PubMedCrossRefGoogle Scholar
  11. 11.
    Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V, Diago M, Marcellin P et al (2004) Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 140(5):346–355PubMedGoogle Scholar
  12. 12.
    Barnes E, Webster G, Jacobs R, Dusheiko G (1999) Long-term efficacy of treatment of chronic hepatitis C with alpha interferon or alpha interferon and ribavirin. J Hepatol 31(Suppl 1):244–249. doi: 10.1016/S0168-8278(99)80410-3 PubMedCrossRefGoogle Scholar
  13. 13.
    Marcellin P, Boyer N, Gervais A, Martinot M, Pouteau M, Castelnau C et al (1997) Long-term histologic improvement and loss of detectable intrahepatic HCV RNA in patients with chronic hepatitis C and sustained response to interferon-alpha therapy. Ann Intern Med 127(10):875–881PubMedGoogle Scholar
  14. 14.
    Poynard T, McHutchison J, Manns M, Trepo C, Lindsay K, Goodman Z et al (2002) Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C. Gastroenterology 122(5):1303–1313. doi: 10.1053/gast.2002.33023 PubMedCrossRefGoogle Scholar
  15. 15.
    Tanaka H, Tsukuma H, Kasahara A, Hayashi N, Yoshihara H, Masuzawa M et al (2000) Effect of interferon therapy on the incidence of hepatocellular carcinoma and mortality of patients with chronic hepatitis C: a retrospective cohort study of 738 patients. Int J Cancer 87(5):741–749. doi:10.1002/1097-0215(20000901)87:5<741::AID-IJC18>3.0.CO;2-BPubMedCrossRefGoogle Scholar
  16. 16.
    Toyoda H, Kumada T, Tokuda A, Horiguchi Y, Nakano H, Honda T et al (2000) Long-term follow-up of sustained responders to interferon therapy, in patients with chronic hepatitis C. J Viral Hepat 7(6):414–419. doi: 10.1046/j.1365-2893.2000.00241.x PubMedCrossRefGoogle Scholar
  17. 17.
    Pham TN, MacParland SA, Mulrooney PM, Cooksley H, Naoumov NV, Michalak TI (2004) Hepatitis C virus persistence after spontaneous or treatment-induced resolution of hepatitis C. J Virol 78(11):5867–5874. doi: 10.1128/JVI.78.11.5867-5874.2004 PubMedCrossRefGoogle Scholar
  18. 18.
    Radkowski M, Gallegos-Orozco JF, Jablonska J, Colby TV, Walewska-Zielecka B, Kubicka J et al (2005) Persistence of hepatitis C virus in patients successfully treated for chronic hepatitis C. Hepatology 41(1):106–114. doi: 10.1002/hep.20518 PubMedCrossRefGoogle Scholar
  19. 19.
    Pham TN, MacParland SA, Coffin CS, Lee SS, Bursey FR, Michalak TI (2005) Mitogen-induced upregulation of hepatitis C virus expression in human lymphoid cells. J Gen Virol 86(Pt 3):657–666. doi: 10.1099/vir.0.80624-0 PubMedCrossRefGoogle Scholar
  20. 20.
    Laskus T, Radkowski M, Wang LF, 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(2):1014–1017. doi: 10.1128/JVI.74.2.1014-1017.2000 PubMedCrossRefGoogle Scholar
  21. 21.
    Laskus T, Radkowski M, Jablonska J, Kibler K, Wilkinson J, Adair D et al (2004) Human immunodeficiency virus facilitates infection/replication of hepatitis C virus in native human macrophages. Blood 103(10):3854–3859. doi: 10.1182/blood-2003-08-2923 PubMedCrossRefGoogle Scholar
  22. 22.
    Reichard O, Glaumann H, Frydén A, Norkrans G, Wejstål R, Weiland O (1999) Long-term follow-up of chronic hepatitis C patients with sustained virological response to alpha-interferon. J Hepatol 30(5):783–787. doi: 10.1016/S0168-8278(99)80129-9 PubMedCrossRefGoogle Scholar
  23. 23.
    Lee WM, Polson JE, Carney DS, Sahin B, Gale M Jr (2005) Reemergence of hepatitis C virus after 8.5 years in a patient with hypogammaglobulinemia: evidence for an occult viral reservoir. J Infect Dis 192(6):1088–1092. doi: 10.1086/432917 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Juan F. Gallegos-Orozco
    • 1
  • Jorge Rakela
    • 2
  • Marianne J. Rosati
    • 2
  • Hugo E. Vargas
    • 2
  • Vijayan Balan
    • 2
  1. 1.Department of Internal MedicineMayo Clinic ArizonaPhoenixUSA
  2. 2.Division of Transplantation MedicineMayo Clinic ArizonaPhoenixUSA

Personalised recommendations