Genetic variation of hepatitis B virus and its significance for pathogenesis

Figure 1 Interventions, mutations and clinical outcomes in the natural history of hepatitis B virus infection. The natural history of hepatitis B virus (HBV) infection is typically classified into 4 phases: immune tolerant, immune clearance, inactive and recovery phase. Patients who receive HBV vaccine and/or hepatitis B immunoglobulin (HBIg) injection may develop chronic HBV infection with PreS and/or S gene mutations, this phenomenon is called occult HBV infection (OBI); during the immune clearance phase, long-term use of NAs can select for mutations in the reverse transcriptase (RT) and S regions; HBV reactivation may occur during the inactive phase in patients with hepatitis B surface antigens (HBsAg) and/or anti-HBc positive after chemotherapy or immunosuppression. HBV isolated from these patients may harbor mutations in the PreS, S, basal core promoter (BCP) or Pre-C regions. The causal relationship between these mutations and chemotherapy or immunosuppression is unclear; with increasing age, some patients can develop BCP, Pre-C or X region mutations or HBV DNA integration leading to hepatitis B e antigen (HBeAg) negativity or tumor.