Journal of Gastroenterology

, Volume 47, Issue 12, pp 1323–1335

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
Original Article—Liver, Pancreas, and Biliary Tract

DOI: 10.1007/s00535-012-0596-x

Cite this article as:
Kondo, Y., Ueno, Y., Ninomiya, M. et al. J Gastroenterol (2012) 47: 1323. doi:10.1007/s00535-012-0596-x

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.

Keywords

Dual infection HBV HCV Immunopathogenesis 

Supplementary material

535_2012_596_MOESM1_ESM.pdf (618 kb)
Supplemental Fig. 1: Sequential analysis of immune-cell subsets during Peg-IFN/RBV therapy. Representative dot plots of NK cells and NKT cells are shown (A). Representative dot plots of activated CD3+ T cells, CD4+ cells and CD8+ cells are shown (B). Representative dot plots of CD4+CD25high Tregs and activated B cells are shown (C). Sequential data of various immune-cell subsets in patient A are shown (D). Sequential data of various immune-cell subsets in patient B are shown (E). Five HCV-monoinfected patients served for the immune cell frequency analysis. The mean frequencies of various immune-cell subsets in five HCV mono-infected patients with Peg-IFN/RBV treatment are shown (F). Error bars indicate standard deviation (PDF 618 kb)
535_2012_596_MOESM2_ESM.xls (35 kb)
Supplementary material 2 (XLS 35 kb)

Copyright information

© Springer 2012

Authors and Affiliations

  • Yasuteru Kondo
    • 1
  • Yoshiyuki Ueno
    • 1
  • Masashi Ninomiya
    • 1
  • Keiichi Tamai
    • 1
  • Yasuhito Tanaka
    • 2
  • Jun Inoue
    • 1
  • Eiji Kakazu
    • 1
  • Koju Kobayashi
    • 3
  • Osamu Kimura
    • 1
  • Masahito Miura
    • 4
  • Takeshi Yamamoto
    • 5
  • Tomoo Kobayashi
    • 6
  • Takehiko Igarashi
    • 7
  • Tooru Shimosegawa
    • 1
  1. 1.Division of GastroenterologyTohoku University Graduate School of MedicineSendaiJapan
  2. 2.Virology and Liver UnitNagoya City University Medical SchoolNagoyaJapan
  3. 3.Tohoku University Graduate School of MedicineSendaiJapan
  4. 4.Department of GastroenterologySouth Miyagi Medical CenterOogawaraJapan
  5. 5.Department of GastroenterologyTohoku Kosei-Nenkin HospitalSendaiJapan
  6. 6.Department of HepatologyTohoku Rosai HospitalSendaiJapan
  7. 7.Department of GastroenterologyOsaki Citizen HospitalOsakiJapan

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