Hepatitis D is caused by the hepatitis D virus (HDV); it is the most severe form of viral hepatitis in humans, running an accelerated course to cirrhosis. There is no efficacious therapy, and liver transplantation provides the only therapeutic option for terminal HDV disease. However, HDV infection is prevalent in poor countries of the world with no access to liver transplant programs; liver grafting has been performed in high-income countries, where the prevalence of the infection has much diminished as a secondary effect of hepatitis B virus vaccination, and the demand for liver transplantation outlives in aging cirrhotics who acquired hepatitis D decades ago. This review describes the evolution of liver transplantation for HDV disease from its inception in 1987 to the present time, with an outlook to its future. It reports the progress in the prophylaxis of HDV reinfections to the success of the current standard of indefinite combination of hepatitis B virus antivirals with immunoglobulins against the hepatitis B surface antigen; however, the unique biology of the virus provides a rationale to reducing costs by limiting the administration of the immunoglobulins against the hepatitis B surface antigen.
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