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

Liver Int. 2011 Oct;31(9):1395-405. doi: 10.1111/j.1478-3231.2011.02593.x. Epub 2011 Jul 15.

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.

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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / 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
  • Hepatitis D, Chronic / drug therapy*
  • Hepatitis D, Chronic / immunology
  • Hepatitis Delta Virus / genetics
  • Hepatitis Delta Virus / immunology*
  • Humans
  • Interferon-alpha / therapeutic use*
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / 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

Substances

  • Antiviral Agents
  • Cytokines
  • Interferon-alpha
  • Organophosphonates
  • RNA, Viral
  • Recombinant Proteins
  • Polyethylene Glycols
  • adefovir
  • Adenine
  • peginterferon alfa-2a