Prophylactic Use of Entecavir for Non-Hodgkin's Lymphoma Patients With Resolved Hepatitis B (HBVNHL)

• The primary endpoint is the incidence of HBV reactivation during and within 12 months after chemotherapy [ Time Frame: Monthly, and till 12 months after chemotherapy ] [ Designated as safety issue: Yes ]
  

• To evaluate the proportion of subjects in each group who discontinue study drug for clinical or laboratory adverse events. [ Time Frame: monthly, till 12 months after chemotherapy ] [ Designated as safety issue: Yes ]
  

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 to receive either prophylactic or therapeutic use of entecavir (0.5 mg/day) during the period of chemotherapy. The primary endpoint is the incidence of HBV reactivation during and within 12 months after chemotherapy. Hepatitis flare is defined as a greater than 3-fold increase of serum ALT level that exceeded 100 IU/L. The hepatitis flare will be attributed to HBV reactivation if it was preceded or accompanied by a greater than 10-fold increase, compared with previous nadir levels, of HBV DNA or by the reappearance of HBsAg in the serum. The secondary endpoints of this current study are the incidence of hepatitis, hepatic failure, and the objective response rate to chemotherapy.