Journal
CURRENT OPINION IN INFECTIOUS DISEASES
Volume 29, Issue 6, Pages 645-653Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QCO.0000000000000321
Keywords
antiviral therapy; hepatitis B virus; hepatitis D virus; liver; viral cycle
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Funding
- ANRS [2011-2, 2013-2]
- INSERM
- French Ministry of Research and Technology grant
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Purpose of review To highlight new concepts and therapeutic approaches concerning hepatitis D virus (HDV) infection. Recent findings Common receptor for hepatitis B virus (HBV) and HDV has been elucidated, deciphering of HDV replication is still in progress, preliminary results of phase II proof-of-concept clinical assays for entry inhibitors and cellular farnesyl transferase inhibitors are now available. Summary Hepatitis D infection remains a severe acute and chronic liver illness with the only currently approved therapy (Peg-alpha IFN) 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 log(10) 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.
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