A Novel HBV Drug for Effective Cure of Chronic Hepatitis B
Abstract:
Hepatitis B and evaluation of curative hepatitis B therapies are listed in FY20 PRMRP Topic Areas and the Areas of Encouragement, respectively. Thisproposal aims to test a new HBV cure therapy and is encouraged by FY20 PRMRP.Current HBV drugs can inhibit HBV replication, but rarely cure chronic hepatitis B (CHB). The reason for this failure is the persistence of HBV cccDNA(covalently closed circular DNA) in infected hepatocytes. A global panel of 35 HBV experts publishes a special paper titled A Research Agenda for CuringChronic Hepatitis B Virus Infection, in which they state that the surest way to cure HBV is to eliminate or permanently silence its cccDNA. Thisrecommended cure strategy clearly assumes no cccDNA clearance with current HBV treatment.However, both nucleot/side analogues (NA) and interferons (IFN) treatments can reduce intrahepatic cccDNA level by 1 to 2.94 log. For instance, averagecccDNA copies were reduced from 1.05 copies per cell at treatment initiation to one copy per 250 cells (0.004 copies per cell) after 48-week of IFN + adefovirtherapy, implying >99% of infected cells clear HBV cccDNA.