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.
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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 deltapatients. 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.
Authors: Joana Dias; Julia Hengst; Tiphaine Parrot; Edwin Leeansyah; Sebastian Lunemann; David F G Malone; Svenja Hardtke; Otto Strauss; Christine L Zimmer; Lena Berglin; Thomas Schirdewahn; Sandra Ciesek; Nicole Marquardt; Thomas von Hahn; Michael P Manns; Markus Cornberg; Hans-Gustaf Ljunggren; Heiner Wedemeyer; Johan K Sandberg; Niklas K Björkström Journal: J Hepatol Date: 2019-05-14 Impact factor: 25.083
Authors: Elizabeth C Townsend; Grace Y Zhang; Rabab Ali; Marian Firke; Mi Sun Moon; Ma Ai Thanda Han; Benjamin Fram; Jeffrey S Glenn; David E Kleiner; Christopher Koh; Theo Heller Journal: J Gastroenterol Hepatol Date: 2019-02-25 Impact factor: 4.029
Authors: Anika Wranke; Benjamin Heidrich; Stefanie Ernst; Beatriz Calle Serrano; Florin Alexandru Caruntu; Manuela Gabriela Curescu; Kendal Yalcin; Selim Gürel; Stefan Zeuzem; Andreas Erhardt; Stefan Lüth; George V Papatheodoridis; Birgit Bremer; Judith Stift; Jan Grabowski; Janina Kirschner; Kerstin Port; Markus Cornberg; Christine S Falk; Hans-Peter Dienes; Svenja Hardtke; Michael P Manns; Cihan Yurdaydin; Heiner Wedemeyer Journal: PLoS One Date: 2014-07-29 Impact factor: 3.240