title: Sequential immunological analysis of HBV/HCV co-infected patients during Peg-IFN/RBV therapy.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, Sendai, Miyagi, Japan.
authors.forename: Yasuteru
authors.initials: Y
authors.lastname: Kondo
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ueno
authors.forename: Masashi
authors.initials: M
authors.lastname: Ninomiya
authors.forename: Keiichi
authors.initials: K
authors.lastname: Tamai
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Jun
authors.initials: J
authors.lastname: Inoue
authors.forename: Eiji
authors.initials: E
authors.lastname: Kakazu
authors.forename: Koju
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Osamu
authors.initials: O
authors.lastname: Kimura
authors.forename: Masahito
authors.initials: M
authors.lastname: Miura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Tomoo
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Takehiko
authors.initials: T
authors.lastname: Igarashi
authors.forename: Tooru
authors.initials: T
authors.lastname: Shimosegawa
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016022:Case-Control Studies; D002478:Cells, Cultured; D060085:Coinfection / Q000188:drug therapy / Q000276:immunology; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D007371:Interferon-gamma; C417083:peginterferon alfa-2b