The hepatitis D satellite virus of hepatitis B virus: half-opening a new era to control viral infection?

Abstract

Hepatitis D infection remains a severe acute and chronic liver illness with the only currently approved therapy (Peg-αIFN) achieving disappointingly low rates of sustained viral response and clinical improvement. Both sodium taurocolate cotransporting polypeptide and heparan sulphate glypican 5 are important for viral adsorption. Preliminary results of 6 months treatment with a subcutaneous HBV PreS1-derived myristoyled peptide as an entry inhibitor indicates an encouraging short-term response with low side-effects. In addition, the short-term use of oral farnesyl transferase inhibitors induces a log10 reduction of viral RNA in almost all treated patients, but is associated with gastrointestinal upset and weight loss (especially using 200 mg/day). Encouraging results are being reported using intravenous phosphorothioate nucleic acid polymers both in terms of HBV surface antigens (HBsAg) and HDV-RNA decline; interestingly, in some patients with a strong HBsAg decline, the appearance of anti-hepatitis Bs antibodies might suggest clinical end-point improvement.

Hepatitis B and hepatitis D virus infections in the Central African Republic, twenty-five years after a fulminant hepatitis outbreak, indicate continuing spread in asymptomatic young adults

“…While HBV is a DNA virus with a reverse transcriptase targeted by antiviral drugs, HDV RNA replicates by hijacking the cellular RNA polymerase II. Therefore, chronic hepatitis due to HBV–HDV is the most difficult-to-treat of all severe virally-induced liver diseases [ 12 – 14 ]. Even though therapeutics are available for chronic HBV or HCV infections, about 15 million HBV–HDV-infected patients worldwide await efficient therapy.…”

“…Alpha-Interferon or Pegylated-IFN that are currently the sole anti-HDV authorized drugs, may be of limited efficacy in less than one third of infected patients. Furthermore, addition of Adefovir or Tenofovir or Entecavir to Pegylated-IFN does not improve the sustained response rate among HDV-1-infected patients, underlining the importance for developing new approaches [ 12 , 14 ]. Indeed, new strategies, such as viral entry competitors, farnesyl transferase inhibitors and nucleic acid polymers are nowadays promising, even if they are still upstream from a wide clinical use [ 14 ].…”