Therapeutic Strategies and New Intervention Points in Chronic Hepatitis Delta Virus Infection

Chronic hepatitis delta virus infection (CHD) is a condition arising from super-infection of hepatitis B virus (HBV)-infected patients, resulting in a more rapid advance in liver pathology and hepatocellular carcinoma than is observed for HBV mono-infection. Although hepatitis delta virus (HDV) is structurally simple, its life cycle involves the complex participation of host enzymes, HBV-derived surface antigen (HBsAg), and HDV-auto-ribozyme and hepatitis delta antigen (HDAg) activities. Unsatisfactory clinical trial results with interferon-based therapies are motivating researchers to adjust and redirect the approach to CHD drug development. This new effort will likely require additional structural and functional studies of the viral and cellular/host components involved in the HDV replication cycle. This review highlights recent work aimed at new drug interventions for CHD, with interpretation of key pre-clinical- and clinical trial outcomes and a discussion of promising new technological approaches to antiviral drug design.