Trial Information

Prophylactic Use of Entecavir for Chemotherapy Associated With Hepatitis B Reactivation in HBsAg (-), Anti-HBc (+) Non-Hodgkin's Lymphoma Patients: a Randomized Controlled Trial

Hepatitis B (HBV) reactivation and hepatitis flare induced by cytotoxic chemotherapy is
common in cancer patients who have chronic HBV infection. It is best characterized in
patients with hematological malignancies such as non-Hodgkin's lymphoma but also can occur
in patients with solid tumors. Reactivation during the initiation of chemotherapy may cause
delay in cancer treatment and decrease in overall survival. The direct mortality caused by
HBV reactivation, predominantly acute liver failure, ranges from 4% to 60%. Based on
currently available information, it is well documented that HBV carriers should receive
antiviral agents to prevent hepatitis B flare before receiving immunosuppressive agents and
chemotherapy. However, development of hepatitis, acute liver failure, and mortality can
occur among patients who are HBsAg negative but anti-HBc positive at the time of
chemotherapy. Therefore, before the initiation of cytotoxic chemotherapy in cases of
non-Hodgkin's lymphoma, it is unknown whether patients previous infected by HBV but negative
HBsAg should routinely receive antiviral agents for prevention of HBV flare. In addition,
the major concern of long-term lamivudine use is the selection of drug-resistant mutations.
Based on these, we designed this current study to address the above important issues.
Eligible patients are newly diagnosed, histologically proven anti-CD20-positive
non-Hodgkin's lymphoma at our hospital. Patients should be negative of HBsAg but positive of
serum anti-HBc. After signing the patient consent form, serum samples will be stored for
further genotyping and quantitative HBV DNA testing. Patients will be randomized into two
groups. In the prophylactic use group, participants will initiate entecavir 0.5 mg/day
orally on day 1 of the first course of chemotherapy. Entecavir treatment will be continued
until 3 months after the completion of chemotherapy and achieving the remission of the
hepatitis (ALT normalization and undetectable HBV DNA). In the therapeutic use group,
patients will start entecavir therapy, 0.5 mg/day orally, only when elevation of ALT (>100
U/L) and HBV DNA (>2000 IU/ml) developed during follow-up, or in the situation of HBsAg
reverse seroconversion, and continued entecavir treatment until hepatitis resolved. The
primary endpoint is the incidence of HBV reactivation during and within 12 months after
completing chemotherapy in diffuse large B cell or follicular lymphoma patients who receive
R-CHOP regimen. The secondary endpoint is the incidence of HBsAg reverse seroconversion
during and within 12 months after completing chemotherapy.