With the increasing use of potent immunosuppressive therapy, reactivation of hepatitis B virus (HBV) in endemic regions is becoming a clinical problem requiring special attention. A recent annual nationwide survey clarified that HBV reactivation related to immunosuppressive therapy has been increasing in patients with
malignant lymphoma, other
hematological malignancies, oncological or rheumatological disease. In the survey,
rituximab plus
steroid-containing
chemotherapy was identified as a risk factor for HBV reactivation in
hepatitis B surface antigen (
HBsAg) negative patients with
malignant lymphoma. In this setting, HBV reactivation resulted in fatal
fulminant hepatitis regardless of the treatment of
nucleoside analog. The Intractable
Hepatobiliary Disease Study Group and the Study Group for the Standardization of Treatment of Viral
Hepatitis Including
Cirrhosis jointly developed guidelines for preventing HBV reactivation. The essential features of the guideline are as follows. All patients should be screened for
HBsAg by a sensitive method before the start of immunosuppressive therapy. Second,
hepatitis B core antigen (HBcAb) and
hepatitis B surface antibody (HBsAb) testing should be performed in
HBsAg negative patients, especially those receiving intensive immunosuppressive therapy. Prophylaxis with
nucleoside analogs is essential for preventing HBV reactivation in
HBsAg positive patients. In contrast,
HBsAg negative with HBcAb and/or HBsAb positive patients should be monitored monthly for an increase in serum HBV
DNA during and 12 months after completion of
chemotherapy.
Nucleoside analogs should be administrated immediately when HBV
DNA becomes positive during this period. This strategy facilitates commencement of
nucleoside analogs at an early stage of HBV reactivation and results in prevention of severe
hepatitis.