Immunopathogenesis of Acute Flare of Chronic Hepatitis B: With Emphasis on the Role of Cytokines and Chemokines

Acute flares (AFs) of chronic hepatitis B usually occur during the immune-active stage (both immune clearance phase and immune reactivation phase), as the host immune system tries to control the virus. Successful host immune control over viral replication is usually presented as hepatitis B surface antigen seroclearance; however, 20–30% individuals with chronic hepatitis B may encounter repeated AFs with accumulative liver injuries, finally leading to the development of cirrhosis and hepatocellular carcinoma. AF can also develop in other clinical situations such as organ transplantation, cancer chemotherapy, and under treatment for chronic hepatitis B or treatment for chronic hepatitis C in patients with co-infected hepatitis B/hepatitis C. Understanding the natural history and immunopathogenesis of AF would help develop effective strategies to eradicate the virus and improve the clinical outcomes of patients with chronic hepatitis B. In this review article, the immunopathogenesis of AF, and the involvement of innate and adaptive immune responses on the development of hepatitis B flare will be briefly reviewed, with the emphasis on the role of cytokines and chemokines.