History and prevention of de novo hepatitis B virus-related hepatitis in Japan and the world

Hepatitis B virus (HBV) replication has been shown to persist at low levels in the liver for decades, even in patients with resolved HBV infection. In these cases, reactivation of HBV and ensuing hepatitis during or after cytotoxic or immunosuppressive therapy is now recognized as de novo HBV-related hepatitis. The occurrence of de novo HBV-related hepatitis has become more frequent after the introduction of rituximab for the treatment of hematological disorders, such as malignant lymphomas. More alarmingly, reactivation can lead to fatal fulminant hepatic failure, indicating a need to establish guidelines to prevent the occurrence of de novo HBV-related hepatitis. It is possible that lamivudine prophylaxis and close surveillance of serum HBV DNA are effective in this regard. However, such measures are currently not available to hepatitis B surface antigen (HBsAg)-negative patients in Japan. A preliminary guideline for preventing HBV reactivation during and after cytotoxic or immunosuppressive therapies was made in 2008 by two collaborative study groups from the Japanese Ministry of Health, Labour, and Welfare, including measures not only for HBV carriers, but also for patients with resolved HBV infection. Since this recommendation is a tentative one, further testing and improvements are being planned.