With an estimated 400 million people suffering from chronic hepatitis B virus, HBV is a serious global health problem. Out of all the people living with chronic HBV infection, 30-40% are immune tolerant, 35-45% have inactive disease and 25%, or about 100 million people, suffer from active disease. 
Patients with inactive disease typically have normal levels of markers of liver injury (normal-ALTs) and low levels of HBV DNA. Patients with active disease are at a greater risk of death from cirrhosis and hepatocellular carcinoma, or liver cancer, and almost 100% of immune tolerant patients will eventually develop active disease as well.
Chronic HBV infection is a leading cause of cancer-related morbidity and mortality worldwide [American Journal of Gastroenterology 2009; 104(7): 1693-9] and it continues to pose one of the most serious and prevalent health problems, accounting for over 1 million deaths annually. New generations of antiviral drugs with novel mechanisms of action are needed to increase the cure rates and decrease the global threat posed by HBV.