Hepatitis B: Who should be treated?-managing patients with chronic hepatitis B during the immune-tolerant and immunoactive phases

New hepatitis B virus (HBV) infections are decreasing owing to improved antiviral therapy and increased HBV vaccination worldwide; however, the number of HBV infections remains a major cause of liver carcinogenesis. HBV triggers cytotoxic immunity to eliminate HBV-infected cells. Therefore, the HBV pathophysiology changes in persistently infected individuals depending on host immune responses and HBV DNA proliferation state. To prevent liver cirrhosis and carcinogenesis caused by HBV, it is important to treat HBV infection at an early stage. Active treatment is recommended for the immunoactive hepatitis B surface-antigen-positive and -negative phase, but not during the immune-inactive phase or immune-tolerant phase; instead, follow-up is recommended. However, these patients should be monitored through regular blood tests to accurately diagnose the immune-inactive or -tolerant phases. The treatment regimen should be determined based on the age, sex, family history of liver cancer, and liver fibrosis status of patients. Early treatment is often recommended due to various problems during the immune-tolerant phase. This review compares the four major international practice guidelines, including those from the Japanese Society of Hepatology, and discusses strategies for chronic hepatitis B treatment during the immune-tolerant, immune-inactive, and resolved phases. Finally, recommended hepatitis B antiviral therapy and follow-up protocols are discussed.