Antiviral therapy of hepatitis delta virus infection - progress and challenges towards cure

Hepatitis B-/D-virus co-infection causes the most severe form of viral hepatitis, frequently leading to liver cirrhosis, hepatic decompensation and consecutive liver-related mortality. Treatment options for hepatitis delta are limited. The only recommended therapy is pegylated interferon alpha which leads to virological responses in about 25-30% of patients. However, interferon therapy is associated with frequent side-effects and late HDV RNA relapses have been described during long-term follow even in patients who were HDV RNA negative 24 weeks after the end of therapy. Thus, alternative treatment options are urgently needed. Clinical studies have been performed exploring prenylation inhibitors, viral entry inhibitors and nucleic acid polymers to block particle release. We here summarize the progress and challenges towards cure of HDV infection.