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Epidemiology, pathogenesis and management of hepatitis D: update and challenges ahead

Abstract

Hepatitis D is caused by infection with the hepatitis D virus (HDV) and is considered to be the most severe form of viral hepatitis in humans. Hepatitis D occurs only in individuals positive for the HBV surface antigen (HBsAg) as HDV is a defective RNA viroid that requires HBsAg for transmission. At least eight different HDV genotypes have been described and each has a characteristic geographic distribution and a distinct clinical course. HDV and HBV coinfection can be associated with complex and dynamic viral dominance patterns. Chronic HDV infection leads to more severe liver disease than HBV monoinfection and is associated with accelerated fibrosis progression, earlier hepatic decompensation and an increased risk for the development of hepatocellular carcinoma. So far, only IFN-α treatment has proven antiviral activity against HDV in humans and has been linked to improved long-term outcomes. Studies conducted in the past 2 years on the use of PEG-IFN-α show that a sustained virologic response to therapy, measured in terms of undetectable serum HDV RNA levels, can be achieved in about one quarter of patients with hepatitis D. Novel alternative treatment options including prenylation inhibitors are awaiting clinical development for use in hepatitis D.

Key Points

  • Hepatitis D occurs only in individuals positive for the HBV surface antigen (HBsAg) as hepatitis D virus (HDV) is a defective RNA viroid that requires HBsAg for transmission

  • Chronic HDV infection is associated with a severe course of hepatitis that frequently leads to rapid fibrosis progression, hepatic decompensation and the development of hepatocellular carcinoma

  • HDV infection is particularly frequent among immigrant populations from regions where HDV is endemic, such as Central Africa, Eastern Turkey, Central Asia, some Eastern European countries and the Amazonian region of Brazil

  • Only IFN-α has proven antiviral activity against HDV and treatment with PEG-IFN-α leads to HDV clearance in about 25% of patients

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Figure 1: Global epidemiology of HDV infection according to viral genotype.
Figure 2: A possible treatment algorithm for hepatitis D.

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Correspondence to Michael P. Manns.

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H. Wedemeyer and M. Manns have received research funding, consulting fees and speaker's honoraria from BMS, Gilead, Novartis and Roche, Schering Plough.

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Wedemeyer, H., Manns, M. Epidemiology, pathogenesis and management of hepatitis D: update and challenges ahead. Nat Rev Gastroenterol Hepatol 7, 31–40 (2010). https://doi.org/10.1038/nrgastro.2009.205

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