Recent treatment advances and practical management of hepatitis D virus

Abstract

Hepatitis D virus (HDV), also referred to as hepatitis delta virus, is the smallest virus capable of causing human disease. It is unable to replicate on its own and can only propagate in the presence of hepatitis B virus (HBV). Infection with both HBV and HDV frequently results in more severe disease than HBV alone, with higher instances of cirrhosis, liver failure and hepatocellular carcinoma (HCC). Thus, there is a need for effective treatment for HDV; however, currently approved treatment options are very limited both in terms of their efficacy and availability. This makes the management of HDV a challenge for physicians. In this review, we look at the background, diagnosis and treatment of HDV, informed by our hospital data, to set out the optimal management of HDV; we also explore novel treatment options for this disease.

Keywords: Hepatitis D virus; bulevirtide; lonafarnib; nucleic acid polymer REP 2139; pegylated interferon.

Fig 1.

Hepatitis D viral life cycle and sites of potential therapies. (1) Hepatitis D virus (HDV) attaches to hepatocytes via interactions between hepatitis D surface antigen protein and sodium taurocholate cotransporting polypeptide (NTCP). (2) HDV ribonucleoprotein (RNP) is translocated to the nucleus by the hepatitis D antigen (HDAg) and (3) HDV replication occurs. (4) The HDV antigenome is transported to the endoplasmic reticulum (ER), where (5) it is translated into small HDAg (S-HDAg) and large HDAg (L-HDAg). (6) L-HDAg is prenylated before assembly. (7) S-HDAg supports HDV replication and is recycled into the nucleus. (8) New RNPs via new HDAg molecules are formed and exported into the cytoplasm. (9) New HDV RNP associates with hepatitis B virus (HBV) envelope proteins and is assembled into HDV virions. (10) HDV virions are released from the hepatocyte via the Golgi apparatus. Figure created with BioRender (biorender.com).