Sequential immunological analysis of HBV/HCV co-infected patients during Peg-IFN/RBV therapy

Yasuteru Kondo, Yoshiyuki Ueno, Masashi Ninomiya, Keiichi Tamai, Yasuhito Tanaka, Jun Inoue, Eiji Kakazu, Koju Kobayashi, Osamu Kimura, Masahito Miura, Takeshi Yamamoto, Tomoo Kobayashi, Takehiko Igarashi, Tooru Shimosegawa

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5 Citations (Scopus)

Abstract

Background: The immunopathogenesis of dual chronic infection with hepatitis B virus and hepatitis C virus (HBV/HCV) remains unclear. The in vivo suppressive effects of each virus on the other have been reported. In this study we aimed to analyze the virological and immunological parameters of HBV/HCV coinfected patients during pegylated interferon/ribavirin (Peg-IFN/RBV) therapy. Methods: One patient with high HBV-DNA and high HCV-RNA titers (HBV-high/HCV-high) and 5 patients with low HBV-DNA and high HCV-RNA titers (HBV-low/HCV-high) were enrolled. Twenty patients monoinfected with HBV and 10 patients monoinfected with HCV were enrolled as control subjects. In vitro cultures of Huh 7 cells with HBV/HCV dual infection were used to analyze the direct interaction of HBV/HCV. Results: Direct interaction of HBV clones and HCV could not be detected in the Huh-7 cells. In the HBV-high/HCV-high-patient, the HCV-RNA level gradually declined and HBV-DNA gradually increased during Peg-IFN/RBV therapy. Activated CD4- and CD8-positive T cells were increased at 1 month of Peg-IFN/RBV-therapy, but HBV-specific IFN-γ-secreting cells were not increased and HBV-specific interleukin (IL)-10 secreting cells were increased. The level of HBV- and HCV-specific IFN-γ-secreting cells in the HBV-high/HCV-high-patient was low in comparison to that in the HBV- or HCV-monoinfected patients. In the HBV-low/HCV-high-patient, HCV-RNA and HBV-DNA rapidly declined during Peg-IFN/RBV therapy. Activated CD4- and CD8-positive T cells were increased, and HBV- and HCV-specific IFN-γ-secreting cells were also increased during Peg-IFN/RBV-therapy. Conclusion: The immunological responses of the HBV-high/HCV-high patient were low in comparison to the responses in HBV and HCV monoinfected patients. Moreover, the response of immune cells in the HBV-high/HCV-high patient during Peg-IFN/RBV therapy was insufficient to suppress HBV and HCV.

Original languageEnglish
Pages (from-to)1323-1335
Number of pages13
JournalJournal of gastroenterology
Volume47
Issue number12
DOIs
Publication statusPublished - 2012 Dec

Keywords

  • Dual infection
  • HBV
  • HCV
  • Immunopathogenesis

ASJC Scopus subject areas

  • Gastroenterology

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  • Cite this

    Kondo, Y., Ueno, Y., Ninomiya, M., Tamai, K., Tanaka, Y., Inoue, J., Kakazu, E., Kobayashi, K., Kimura, O., Miura, M., Yamamoto, T., Kobayashi, T., Igarashi, T., & Shimosegawa, T. (2012). Sequential immunological analysis of HBV/HCV co-infected patients during Peg-IFN/RBV therapy. Journal of gastroenterology, 47(12), 1323-1335. https://doi.org/10.1007/s00535-012-0596-x