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Hepatitis D virus-specific cytokine responses in patients with chronic hepatitis delta before and during interferon alfa-treatment.

AbstractBACKGROUND:
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.
CONCLUSION:
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.
AuthorsJan Grabowski, Cihan Yurdaydìn, Kalliopi Zachou, Peter Buggisch, Wolf P Hofmann, Jerzy Jaroszewicz, Verena Schlaphoff, Michael P Manns, Markus Cornberg, Heiner Wedemeyer, HIDIT-1 study group
JournalLiver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 31 Issue 9 Pg. 1395-405 (Oct 2011) ISSN: 1478-3231 [Electronic] United States
PMID21762356 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Copyright© 2011 John Wiley & Sons A/S.
Chemical References
  • Antiviral Agents
  • Cytokines
  • Interferon-alpha
  • Organophosphonates
  • RNA, Viral
  • Recombinant Proteins
  • Polyethylene Glycols
  • adefovir
  • Adenine
  • peginterferon alfa-2a
Topics
  • Adenine (analogs & derivatives, therapeutic use)
  • Adult
  • Analysis of Variance
  • Antiviral Agents (therapeutic use)
  • Cells, Cultured
  • Chi-Square Distribution
  • Cytokines (blood)
  • Drug Therapy, Combination
  • Europe
  • Female
  • Hepatitis D, Chronic (diagnosis, drug therapy, immunology)
  • Hepatitis Delta Virus (genetics, immunology)
  • Humans
  • Interferon-alpha (therapeutic use)
  • Leukocytes, Mononuclear (immunology, virology)
  • Male
  • Middle Aged
  • Organophosphonates (therapeutic use)
  • Polyethylene Glycols (therapeutic use)
  • RNA, Viral (blood)
  • Recombinant Proteins (therapeutic use)
  • Time Factors
  • Treatment Outcome
  • Viral Load
  • Young Adult

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