Background: Fulminant liver failure (FLF) is a potentially fatal complication of hepatitis B reactivation in patients who receive rituximab and cytotoxic chemotherapy. Often patients receiving these regimens are treated with curative intent (e.g. diffuse large cell Non Hodgkin’s lymphoma, adjuvant chemotherapy for breast cancer) and thus avoidance of this complication is desirable. The only known treatment for fulminant liver failure is orthotropic liver transplant. We have developed a cost-effective approach to avoiding FLF. Methods: NCCN recommends screening for hepatitis B serologies in any patient who is to receive Rituximab therapy. Review of the literature regarding fulminant liver failure and cytotoxic chemotherapy revealed that the regimens most strongly associated with reactivation of HepB and fulminant liver failure included doxorubicin and high dose of cyclophosphamide—we have targeted Hepatitis B screening to patients receiving these two chemotherapy drugs. We target patients either felt to have a high probability of occult hepatitis B are screened—these include patients who have had a blood transfusion in a foreign country, those with a transfusion more than 20 years ago, and those patients where Hepatitis B can be passed vertically—including first and second generation Asian American immigrants. Patients deemed at high risk are checked for Hepatitis B surface Antigen and Hepatitis B Core antibodies. No routine imaging is performed. Patients who are HepBSag or HepBCoreAb positive who are to receive high risk chemo/immunotherapy are then started on entecavir 0.5 mg/d two weeks before starting therapy and this is continued for 6 months after completion of therapy. Patients who are HepBAg- and HepBCab+ are monitored with HBV DNA levels monthly during therapy with initiation of entecavir if HBV DNA becomes detectable. Results: Patients receiving chemo/immunotherapy associated with Hep B reactivation can be safely identified and given prophylactgic entecavir treatment. Conclusions: We have created a value-driven cost effective approach to minimizing FLF in patients receiving chemo/immunotherapy. Cost estimates based on US pricing will be presented.