Patients receiving chemotherapy are at risk for reactivation of the hepatitis B virus (HBV), and this can have a significant negative impact on the outcomes, including death from liver failure. According to Emmy Ludwig, MD, of Memorial Sloan-Kettering Cancer Center (MSKCC), New York, one-third of the world has been exposed to HBV, “making it an enormous problem.”
Fortunately, HBV reactivation can be prevented with the prophylactic use of effective antiviral agents, for which recommendations were presented by Ludwig at the 16th Annual Conference of the National Comprehensive Cancer Network.
Although reactivation can occur spontaneously, it typically occurs as a result of immunosuppressive therapies in cancer, autoimmune disease, and organ transplantation. The risk does not end when chemotherapy is completed, but persists for at least 6 months, possibly longer in stem cell transplant patients and in those receiving rituximab (Rituxan). The risk of liver failure from HBV reactivation has been linked to the use of rituximab—precipitating a black-box warning for these patients.
Recommendations for Screening and Prophylaxis
Antiviral prophylaxis can prevent chemotherapy-related HBV reactivation. A systematic review of 14 studies (Loomba R, et al.Ann Intern Med. 2008;148:519-528) evaluated the use of lamivudine (Epivir) in patients with chemotherapy who tested positive for the hepatitis B surface antigen (HBsAg). Of 108 patients who received lamivudine prophylactically, none developed HBV reactivation or HBV-related liver failure. Other studies made similar findings among patients with cancer.
Lamivudine was used in many of the earlier studies and is effective; however, most patients will become resistant to lamivudine at 5 years, Ludwig noted. “We do not recommend lamivudine because of the high resistance rate,” she said.
Newer agents such as entecavir (Baraclude) are extremely effective, have less propensity for resistance, and are less likely to interact with other medications. Entecavir, therefore, is the preferred antiviral at MSKCC, she said.
In March 2009, MSKCC initiated HBV screening of all new patients receiving immunosuppressive therapy. Among 4065 patients screened from May 2009 to September 2010, almost 10% tested positive for either the HBsAg or the hepatitis B core antibody (HBcAb). All of these patients were treated with antiviral prophylaxis, and none experienced HBV reactivation.
The evidence of potential benefit has led many medical groups to endorse HBV screening for patients receiving immunosuppressive therapy, including the American, European, and Asian-Pacific Associations for the Study of Liver Diseases; the Infectious Disease Society of America; the American Gastroenterology Association; the American College of Rheumatology; and the Centers for Disease Control and Prevention.
The National Comprehensive Cancer Network (NCCN) suggests that antiviral therapy “be strongly considered in patients with acute HBV infection undergoing hematopoietic stem cell transplant or other intensive immunosuppression,” although this is based on limited data, the group acknowledged. Also in its Clinical Practice Guidelines for Non-Hodgkin’s Lymphomas (V.2.2011), the NCCN recommends HBsAg and HBcAb screening for all patients receiving rituximab.
But such recommendations are not universal, most notably, routine screening is not recommended by the American Society of Clinical Oncology (ASCO). ASCO deems the evidence to be “insufficient to determine the net benefits and harms of routine screening for chronic HBV infection in individuals with cancer who are about to receive cytotoxic or immunosuppressive therapy or who are already receiving therapy” (Artz AS, et al. J Clin Oncol. 2010;28:3199-3202).
Ludwig said that despite the reservations in ASCO’s Provisional Clinical Opinion, she personally recommends universal screening. “The data, honestly, are imperfect, and there are no large, randomized trials. However, if I had hepatitis B and were getting chemotherapy, I would put myself on an antiviral,” she commented.” Screening is straightforward and cost-effective, antiviral prophylaxis for HBV works, and prevention is better than treatment,” she pronounced.