Abstract
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.
Highlights
When acquired early in life, the course of the chronic hepatitis B (CHB) can be separated into four stages, namely immune tolerance phase (indicated by hepatitis B e antigen [HBeAg] positivity, high serum hepatitis B virus (HBV) DNA levels, normal serum alanine aminotransferase [ALT] levels, and normal or minimal change of liver histology), immune clearance phase, immune control phase and reactivation phase [1,2,3]
Acute flares (AFs) or acute exacerbations (AEs) of chronic hepatitis B associated liver damage usually occur during the immune-active stage, as the host immune system tries to control the virus and kill virus-infected hepatocytes [2,3]
AF can develop in various clinical situations such as organ transplantation, cancer chemotherapy, treatment for chronic hepatitis B, and treatment for chronic hepatitis C by using direct acting antiviral (DAA) in HBV/hepatitis C virus (HCV) co-infected patients [3,15,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45]
Summary
When acquired early in life, the course of the chronic hepatitis B (CHB) can be separated into four stages, namely immune tolerance phase (indicated by hepatitis B e antigen [HBeAg] positivity, high serum hepatitis B virus (HBV) DNA levels, normal serum alanine aminotransferase [ALT] levels, and normal or minimal change of liver histology), immune clearance phase (positive for HBeAg, intermittent elevation of serum ALT levels, and intermittent elevation of serum HBV DNA levels), immune control phase (negative for HBeAg, serum HBV DNA levels
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