Exploring New Therapies for a Serological Cure of Chronic Hepatitis B

Chronic hepatitis B is a global health issue, as WHO estimates about 240 millions in the world. Without antiviral therapies, a quarter of the HBV carriers will eventually succumb to cirrhosis or hepatocellular carcinoma (Fattovich et al. 2004; Di Bisceglie 2009; Beasley 1988; Liaw et al. 1988). Active therapies have been developed, such as pegylated interferon and antiviral nucleos(t)ide analogs, in the last 20 years (Belloni et al. 2012; Papatheodoridis et al. 2002; Lau et al. 2005). Despite of an effective control of HBV replication by long-term NA treatments, the success of eliminating intrahepatic HBV or infected hepatocytes remains low (about 1–10% of treated patients). A search for novel, curative antiviral therapies has been actively taken up in many institutes. Practically, current NA therapies effectively eliminate extracellular virions, and so the next step will be to eliminate the intracellular viral RNAs, viral proteins, or eventually viral DNAs. The theme has become a more and more important medical task, especially after the advent of highly effective direct antiviral agents curing essentially hepatitis C. Therefore, there are many excellent reviews on the HBV life cycle or immunology that point out or summarize possible targets for future antiviral development (Lanford et al. 2013; Isogawa et al. 2005; Ma et al. 2015; Tang et al. 2016; Petersen et al. 2016). This chapter will skip these overlapping parts but only describe certain exploratory experiments toward novel targets ongoing. The main approach is to develop antiviral immunotherapies which can eradicate intrahepatic HBV DNAs or the HBV-infected hepatocytes in the near future.