Hepatitis delta virus: From biological and medical aspects to current and investigational therapeutic options

•Co-infection with hepatitis B and hepatitis D virus affect 15–20 million people and leads to aggressive liver disease.•The only approved treatment relies on the relatively inefficient interferon-alpha.•Further work is needed to identify new direct and indirect antiviral targets for HDV therapy.•Better understanding of HBV/HDV pathogenesis is needed to delay disease progression and prevent death. An estimated 15–20million individuals are co-infected by hepatitis B and hepatitis D virus worldwide and are at high risk of developing end-stage liver disease, including hepatocellular carcinoma. While HBV viremia can now be controlled in the vast majority of individuals by nucleoside analogs, leading to a delay of disease progression, HDV treatment has for long relied on the relatively inefficient and not well-tolerated interferon-alpha. While the epidemiology and pathogenesis of the disease remain to be precisely determined, using adequate diagnostic tools and well-designed cohort studies, basic research efforts have led to interesting progress in the understanding of HDV biology, which is not yet sufficient to identify specific antiviral targets. More resources now need to be devoted to the HDV field to achieve therapeutic breakthroughs. In this manuscript, we carefully review the literature regarding the biology of hepatitis D virus, the disease, its prevention, current treatments and investigational strategies. This article forms part of a symposium in Antiviral Research on “An unfinished story: from the discovery of the Australia antigen to the development of new curative therapies for chronic hepatitis B.”