Therapeutic Direction and Issues Regarding HBV Infection

With up to 400 million affected people worldwide, chronic hepatitis B virus (HBV) infection is still a major health care problem. During the last decade, several novel therapeutic approaches have been developed and evaluated. In most regions of the world, interferon-α (IFN-α), and nucleos(t)ide analogues are currently approved. Despite major improvements, none of the existing therapies is optimal since viral clearance is rarely achieved. HBV establishes a stable nuclear covalently closed circular DNA (cccDNA). Interferon-α treatment can clear HBV but is limited by systemic side effects. Up-regulation of APOBEC3A and APOBEC3B enzymes by use of IFN-α or lymphotoxin-b (LT bR) was found to result in cytidine deamination, apurinic/apyrimidinic site formation, and finally cccDNA degradation that prevented HBV reactivation, while genomic DNA was found to remain intact. As such, development of new therapeutics in combination with existing antivirals, may cure hepatitis B. With respect to the selectivity observation on the activation of LTβR, however, more studies are necessary on the potential utility of LTβR agonists for clearance of cccDNA in chronic hepatitis B (CHB). HBV is a DNA virus that can integrate DNA into host genome thereby increases the yield of trans-activator protein HBxAg that may deregulate many pathways involving in metabolism of cells causing Hepatocellular Carcinoma (HCC) development. This review aimed at therapeutic direction and issues regarding HBV infection.