NOVEL THERAPIES FOR HEPATITIS B VIRUS - A STEP CLOSER TO CURE?

Chronic hepatitis B virus (HBV) infection affects 350 million people worldwide, representing a significant challenge to public health. Nucleos/tide analogues (NUCs) and the immunomodulatory agent interferon alpha (IFNa), the current standard of care for chronic infection, aim at preventing progression of the disease to end-stage liver disease, hepatocellular carcinoma (HCC) and death. However, in contrast to the case of hepatitis C infection, in which novel antiviral drugs cure the vast majority of treated patients, in regards to HBV, cure is rare due to the unusual persistence of viral DNA in the form of covalently closed circular DNA (cccDNA) within the nucleus of infected cells. Therefore, available therapies for HBV require lifelong treatment and surveillance, as reactivation frequently occurs following medication cessation and the occurrence of HCC is decreased but not eliminated, even after years of successful suppression of viremia. Progress has been made in the development of new therapeutics against chronic HBV infection, and it is likely that only a combination of immune modulators, inhibitors of gene expression and replication and cccDNA-targeting drugs will have the best chance to eradicate chronic infection. This overview aims to summarize the state of the art in HBV drug research highlighting those agents with the greatest potential for success based on in vitro as well as on data from clinical studies.