Section Review: Anti-infectives: Recent developments in the treatment of hepatitis D infection

Abstract

Chronic hepatitis D is an often severe form of liver disease, due to infection with the hepatitis delta virus (HDV), a unique RNA virus that requires the hepatitis B virus (HBV) helper function to exert its pathogenic potential. Alpha IFN is at present the only choice of treatment for chronic HBV/HDV infection, but the results obtained are far from satisfactory. Available data show that IFN is more effective if administered to patients with a recent infection (lasting < 1 year) at high doses (9 - 10 MU thrice weekly) and for a prolonged period of time (12 months). Long-term response is associated with the clearance of hepatitis B surface antigen (HBsAg) from serum, an event which can occur at the end of treatment or even months after treatment discontinuation. On treatment, clearance of HDV-RNA and reduction of alanine aminotransferase (ALT) levels to normal values do not predict long-term response. Prolonged administration of high IFN doses can induce severe psychiatric side-effects, sometimes leading to suicide. IFN should therefore be given for no longer than 12 months and under careful medical supervision. Better therapeutic options are clearly needed. The association of HBV with HDV infection suggests that treatment with the new deoxynucleotide analogues should be considered. Antisense oligonucleotides directed against the self-cleavage domain of HDV-RNA, which can disrupt HDV replication in vitro, may represent the new frontier of HDV therapy.