Hepatitis delta: Epidemiology to recent advances in therapeutic agents

Abstract

Hepatitis D virus (HDV) was first described in 1977 and is dependent on the presence of hepatitis B surface antigen (HBsAg) for its entry into cells and on the human host for replication. Due to the envelopment with the hepatitis B virus (HBV) envelope, early phases of HDV entry resemble HBV infection. Unlike HBV, HDV activates innate immune responses. The global prevalence of HDV is estimated to be about 5% of HBsAg positive individuals. However, recent studies have described a wide range of prevalence between 12 to 72 million individuals. Infection can occur as super-infection or co-infection. The diagnosis of active HDV infection involves screening with anti HDV antibodies followed by quantitative PCR testing for HDV RNA in those who are HBsAg positive. The diagnostic studies have evolved over the years improving the validity and reliability of the tests performed. HDV infection is considered the most severe form of viral hepatitis and the HDV genotype may influence the disease course. There are eight major HDV genotypes with prevalence varying by geographic region. HDV treatment has been challenging as HDV strongly depends on the host cell for replication and provides few, if any viral targets. Better understanding of HDV virology has led to the development of several therapeutic agents currently being studied in different phase II and III clinical trials. There is increasing promise of effective therapies that will ameliorate the course of this devastating disease.

HDV: Epidemiology, lifecycle, testing, and treatment

“…It is unclear where HDV RNA is sensed as replication occurs in the nucleus but the innate immune sensors are located in the cytoplasm (Figure 1). 1 …”

“…It blocks the viral receptor on the hepatocyte and prevents new infections as well as protects naïve hepatocytes. [1] It has been approved for use in chronic HDV in Europe. [12] One study in a real-world cohort in Germany showed virologic response in 87 of the 114 patients in the study.…”

“…HDV is enveloped by the HBV envelope which can attach to heparan sulfate proteoglycans on host cells and then specifically bind to sodium taurocholate cotransporting polypeptide, similar to HBV infection. The subsequent steps of fusion and transport to the nucleus are not well understood and thought to differ between HDV and HBV 1 . The HDV ribonucleoprotein complex, which is composed of circular HDV RNA as well as the large extended and small hepatitis D antigen, is then transported to the nucleus for replication.…”

“…Although awareness of HDV has increased, there is a lack of standardized screening and assays that have led to widely differing published prevalence. [1] CURRENT EPIDEMIOLOGY Over the last 20 years, since the implementation of HBV vaccination programs, studies have suggested the overall prevalence of HDV has declined in the developed world. [2] In high-income countries, HDV is primarily detected in young immigrants from endemic regions.…”

Deciphering the Role of Post-Translational Modifications and Cellular Location of Hepatitis Delta Virus (HDV) Antigens in HDV-Mediated Liver Damage in Mice

“…HDV-infected patients have a higher risk of developing cirrhosis and hepatocellular carcinoma (HCC) as well as hepatic decompensation and increased mortality in comparison with HBV mono-infected patients [ 27 ]. Despite the severity of this disease, the underlying mechanism is still unknown and hence there is a lack of effective treatments to control HDV-induced liver damage [ 28 ]. One of the main reasons for the scarce knowledge of the molecular mechanism/s involved in the pathology of this disease is the absence of adequate animal models that resemble the main pathological features observed in HDV patients and are amenable to experimentation [ 29 ].…”