Chronic Hepatitis D—What Is Changing?

David Yardeni; Theo Heller; Christopher Koh


J Viral Hepat. 2022;29(4):240-251. 

In This Article

Discovery and Epidemiology

It has been more than 40 years since initial reports of a new antigen found in HBV patients in Torino, Italy, that presented with severe liver disease were met with skepticism.[3] The antigen coined by Mario Rizzetto and colleagues with the Greek letter δ (delta) was discovered in the nuclei of infected hepatocytes.[4] Analysis of the patients' serum was positive for the detection of a corresponding antibody. Further studies performed at the National Institutes of Health on chimpanzees were able to discover a previously unidentified human RNA virus.[5] Finally, in 1986, Wang and colleagues were able to characterize the genetic structure and sequence of the now termed hepatitis Delta or HDV.[6] The virus is now recognized as the only member of the Deltaviridae family, genus Deltavirus. Following the discovery of this pathogen, it became apparent that HDV causes chronic viral hepatitis that is much more severe than the one associated with HBV monoinfection with higher rates of deterioration towards HCC, cirrhosis and mortality at a younger age.[7] Unlike HBV which is estimated to infect over 248 million people worldwide,[8] it is estimated that the prevalence of HDV is much lower. The common assumption was that only 15–20 million people, about 5% of chronic HBV patients, are co-infected with HDV.[9] Whilst this percentage may be true in the western world,[10–12] a much higher percentage of HDV co-infection is prevalent in South America,[13] Africa[14] and Asia.[15] However, changes in immigration patterns, particularly of young immigrants with HDV are currently changing the disease epidemiology in the western world.[16] Whilst the true global prevalence remains unknown, a recent systematic review and meta-analysis from 2019 claimed that a much higher worldwide prevalence of HDV/HBV co-infection exists, estimating the number of infected individuals at 62–72 million people. Further complicating the estimated prevalence of HDV is suboptimal testing. Several epidemiology studies in the United States and a recent study from Spain[17] have shown insufficient testing for the HDV antibody (anti-HD) among HBV-infected patients.[10,18] Furthermore, even when testing for HDV is employed, there are considerable differences in the detection rate of HDV RNA between different laboratories worldwide.[19]