The ideal endpoint of HDV treatment should be loss of the HBsAg and of the covalently closed circular HBV DNA (cccDNA) in the nucleus of infected hepatocytes. However, this is rarely attainable with currently available treatments.
The goal of available therapy is to improve quality of life and survival by preventing the progression of the disease. Patients should be considered for treatment when they have detectable HDV RNA levels, elevated ALT levels and moderate to severe active necroinflammation and/or moderate fibrosis, assessed using a standardized scoring system.
Interferon-alpha (a biological drug that consist of a protein produced by the immune system against viral infection) seems effective in suppressing viral and disease activity in some patients when given for one year or more, but this response is not sustained in a majority of patients. According to clinical trials, pegylated interferon-alpha is considered superior to conventional interferon. It can lead to sustained HDV RNA suppression at 24 weeks post-treatment in about a quarter of patients. The main challenge of developing new treatments for HDV is the fact that the virus uses host enzymes for replication and therefore there are few virus-specific targets for therapeutics.
Combination treatments of standard or pegylated interferon with lamivudine, ribavirin, adefovir, tenofovir, and entecavir have been explored but proved disappointing. Emerging treatment options include the prenylation inhibitor lonafarnib, the HBV entry inhibitor bulevirtide, nucleic acid polymers, and lambda interferon which are all currently in Phase II or III of clinical trials. The drugs are being studied individually and in combination with pegylated interferon.
Author: Minaam Abbas