Pathogenesis of Hepatitis B Virus (HBV)-Mediated Liver Injury

Abstract

As a “stealth” virus, hepatitis B virus (HBV) is not directly cytopathic for infected hepatocytes. Hepatic injury is due primarily to the response of the body’s immune system to either acute or chronic infection with HBV. In general, two types of host’s responses occur to viral infection, i.e., innate immune response and adaptive immune response. Current evidence suggests that the innate immune response does not play an important role either in HBV clearance or in liver injury. In contrast, the adaptive immune response mediated by cytotoxic T-lymphocyte (CTL) cells is kinetically associated with viral clearance and liver injury. This observation suggests that the pathogenesis of HBV is closely related to the CTL-mediated immune response. One important way in which CTL cells mediate viral clearance is to secrete serine protease granzymes such as granzyme A and granzyme B which lead to the apoptosis of infected cells. However, HBV replication can upregulate the expression of apoptosis inhibitors such as serine protease inhibitor Kazal, or SPIK, resulting in the resistance of the cells to CTL-mediated immune killing. The inability of the immune system to clear HBV-infected cells can lead to chronic hepatitis B and development of HBV cirrhosis and hepatocellular carcinoma.