title: Hepatitis D virus-specific cytokine responses in patients with chronic hepatitis delta before and during interferon alfa-treatment.
abstract: BACKGROUND
  Hepatitis delta is caused by infection with the hepatitis D virus (HDV) and is considered the most severe form of viral hepatitis. Treatment options for hepatitis delta are limited, with only 25% of patients responding to interferon (IFN)-alfa-based therapies. The role of the adaptive immune system in controlling HDV infection during spontaneous or treatment-induced viral clearance is not well understood.
  
  
  METHODS
  We studied HDV-specific cytokine production of peripheral blood mononuclear cells stimulated with HDV peptide pools as well as serum cytokine levels in well-characterized patients with chronic HDV infection before and during pegylated-interferon-alfa±adefovir therapy.
  
  
  RESULTS
  Hepatitis D virus-specific interleukin (IL)-2, IFN-γ-, interferon-inducible protein-10 and IL-10-responses were detectable in 53%, 35%, 65% and 6% of hepatitis delta patients. HDV-specific IFN-γ responses tended to be more common in patients with low HDV viral loads. HDV-specific cytokine responses declined during pegylated (PEG)-IFNa therapy and patterns of changes were associated with the treatment response. Serum cytokine levels also showed distinct changes during PEG-IFNa treatment.
  
  
  CONCLUSIONS
  We suggest that cellular HDV-specific immune responses contribute to the control of HDV infection and that cytokine responses may indicate response to type-I-IFN-based antiviral therapy of hepatitis delta.
authors.affiliation: Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Grabowski
authors.forename: Cihan
authors.initials: C
authors.lastname: Yurdaydìn
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Zachou
authors.forename: Peter
authors.initials: P
authors.lastname: Buggisch
authors.forename: Wolf P
authors.initials: WP
authors.lastname: Hofmann
authors.forename: Jerzy
authors.initials: J
authors.lastname: Jaroszewicz
authors.forename: Verena
authors.initials: V
authors.lastname: Schlaphoff
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.forename: Markus
authors.initials: M
authors.lastname: Cornberg
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D000704:Analysis of Variance; D000998:Antiviral Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D016009:Chi-Square Distribution; D016207:Cytokines / Q000097:blood*; D004359:Drug Therapy, Combination; D005060:Europe; D005260:Female; D019701:Hepatitis D, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D003698:Hepatitis Delta Virus / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D016898:Interferon-alpha; D063065:Organophosphonates; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C053001:adefovir; D000225:Adenine; C100416:peginterferon alfa-2a