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

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.