Specific Considerations in the Design of Hepatitis B Virus Clinical Studies in the Far East

Seventy-five percent of the world’s population of approx 400 million hepatitis B virus (HBV) carriers are Asians (1 ,2 ). It is therefore not surprising that the majority of clinical studies of HBV infection is from Asian countries or consists of a large proportion of Asians. Because of the difference in the time of acquiring HBV between patients in the East and West, the profile of the HBV disease and treatment response are significantly different. In the East, nearly all HBV patients acquire the disease at birth or during the perinatal/early childhood period (3 ). The HBV infection is followed by a prolonged period of immunotolerance that can last for several decades. This is followed by another prolonged period of immune clearance that may result in severe damage to the liver and its architecture. As a consequence of this, hepatitis B e antigen (HBeAg) seroconversion does not necessarily prevent the development of cirrhosis-related complications and hepatocellular carcinoma (HCC) in Asians. In fact, the majority of cirrhosis-related complications and HCC develops after HBeAg seroconversion (4 ,5 ). Achieving a relatively low viremia state with HBeAg seroconversion is not enough to stop disease progression in Asians with chronic HBV infection.