New therapeutic strategies to treat chronic hepatitis D are directed to deprive the
hepatitis D virus (HDV) of functions necessary to complete its life cycle that are
provided by the hepatitis B virus (HBV) and by the host. Current options are (1) the
block by the synthetic peptide Myrcludex B of HBV surface antigen (HBsAg) entry into
cells through the inhibition of the sodium taurocholate cotransporting receptor; (2)
the inhibition with lonafarnib of the farnesylation of the large HD antigen, required
for virion assembly; (3) the presumed reduction by the nucleic acid polymer REP 2139
of the release of the HBsAg and subviral HBV particles necessary for HD virion morphogenesis.
Lonafarnib and Myrcludex in monotherapy reduced serum HDV-RNA but did not reduce the
HBsAg and HD viremia rebounded after therapy; they may provide additional efficacy
to pegylated interferon alpha (Peg IFN-α) therapy. Treatment with REP-2139 in combination
with Peg IFN-α induced a sustained clearance both of the HDV-RNA and HBsAg in 5 of
12 patients, providing the best interim results so far obtained in the therapy of
chronic hepatitis D.
Keywords
hepatitis D virus - chronic hepatitis D - Lonafarnib - Myrcludex B - REP 2139 - HDV
therapy
