New therapies for chronic hepatitis B.

Approximately 350 million people worldwide are chronically infected with hepatitis B virus (HBV), representing a significant public health challenge. Nucleos/tide analogues (NUCs) and interferon alpha (IFNα), the current standard of care for chronic infection, aim at preventing progression of the disease to cirrhosis, hepatocellular carcinoma (HCC) and death. However, in contrast to the case of hepatitis C virus infection, in which novel antiviral drugs cure the vast majority of treated patients, in regard 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. 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 viral suppression. Progress has been made in the development of new therapeutics, and it is likely that only a combination of immune modulators, inhibitors of gene expression and replication and cccDNA-targeting drugs will eradicate chronic infection. This review 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.

Advances and Challenges in Studying Hepatitis B Virus In Vitro.

Hepatitis B virus (HBV) is a small DNA virus that infects the liver. Current anti-HBV drugs efficiently suppress viral replication but do not eradicate the virus due to the persistence of its episomal DNA. Efforts to develop reliable in vitro systems to model HBV infection, an imperative tool for studying HBV biology and its interactions with the host, have been hampered by major limitations at the level of the virus, the host and infection readouts. This review summarizes major milestones in the development of in vitro systems to study HBV. Recent advances in our understanding of HBV biology, such as the discovery of the bile-acid pump sodium-taurocholate cotransporting polypeptide (NTCP) as a receptor for HBV, enabled the establishment of NTCP expressing hepatoma cell lines permissive for HBV infection. Furthermore, advanced tissue engineering techniques facilitate now the establishment of HBV infection systems based on primary human hepatocytes that maintain their phenotype and permissiveness for infection over time. The ability to differentiate inducible pluripotent stem cells into hepatocyte-like cells opens the door for studying HBV in a more isogenic background, as well. Thus, the recent advances in in vitro models for HBV infection holds promise for a better understanding of virus-host interactions and for future development of more definitive anti-viral drugs.