Hepatitis B core antibody (anti-HBc) is an important marker of prior HBV exposure and potential viral persistence. During acute HBV infection, anti-HBc IgM is the earliest antibody to appear shortly after HBsAg, usually lasting for 6 — 12 months, followed by anti-HBc IgG. In patients with chronic infection experiencing acute hepatitis flares, anti-HBc IgM may reappear, though typically at lower titers than in acute infection. “Isolated anti-HBc positivity” may indicate resolved/functional cure of prior HBV infection or occult HBV infection, and there is still a risk of HBV reactivation or transmission during chemotherapy, immunotherapy, blood transfusion, or organ transplantation. Therefore, accurate recognition of the clinical significance of anti-HBc is essential for comprehensive evaluation and individualized management of HBV infection.