Overview of the immunological mechanisms in hepatitis B virus reactivation: Implications for disease progression and management strategies

Figure 1 Reactivation mechanism of hepatitis B virus. Immune control phase: B cells produce antibodies against hepatitis B virus (HBV) and prevent the transmission of HBV infection among hepatocytes; HBV covalently closed circular DNA is persistent in hepatocytes; HBV-specific T-cells limit viral replication via both cytopathic effects and non-cytopathic cytokine pathways. Immunological suppression phase: HBV DNA replicates again due to treatment-induced loss of immunological control; T-cells and B-cells are suppressed or destroyed by immunosuppressive therapies. HBV mutations cause immunological escape from T cells specific to HBV, and HBV DNA replicates again. When HBV DNA actively amplifies in vivo, HBV reactivation takes place. T-cells, the immune system’s reconstruction, and the active immunological phase target HBV-DNA and infected hepatocytes. The damaged hepatocytes release aspartate aminotransferase and alanine aminotransferase. cccDNA: Covalently closed circular DNA; HBV: Hepatitis B virus; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase.