Fatal hepatitis B reactivation due to everolimus in metastatic breast cancer: case report and review of literature

Abstract

Hepatitis B reactivation can occur with cytotoxic chemotherapy in patients with hepatitis B and cancer. Reactivation can occur in a patient with chronic hepatitis, an inactive carrier, or one with resolved hepatitis. Clinical presentation may range from subclinical elevation of liver enzymes to fatal fulminant hepatic failure. Mammalian target of rapamycin inhibitors, which include everolimus, are a new generation of targeted agents that are currently approved for many cancers (since March 2009) including advanced hormone receptor positive, human epidermal growth factor receptor 2-negative breast cancer, in conjunction with exemestane (as of July 2012). We are therefore still learning the various adverse events that occur with this new class of agents. Here, we present an unfortunate case of fatal hepatitis B reactivation in a woman with metastatic breast cancer treated with everolimus and exemestane. We have detailed the controversies around hepatitis B screening prior to immunosuppressive therapy. Clinicians and patients should be aware of this rare but fatal complication prior to everolimus use, and a detailed history, screening for hepatitis B and prophylactic antiviral treatment should be considered.

Hepatotoxicity of targeted therapy for cancer

“…Reactivation of HBV has been reported with the BCR-ABL inhibitors imatinib and nilotinib, and the mTOR inhibitor everolimus that required salvage with liver transplant or were fatal. [84][85][86][87][88][89][90][91] Similar fatal cases of fulminant HBV reactivation has occurred with the anti-CD20 group of MAbs and Alemtuzumab. [92-98, Table 3].…”

Review article: preventing hepatitis B graft infection in hepatitis B patients after liver transplantation: immunoglobulin vs anti‐virals

“…However, HBcAb+/HBsAb+ recipients with HBcAb+ donor grafts might receive a finite NA prophylaxis for the first 12 months post‐LT when the degree of immunosuppression is the highest. In addition to calcineurin inhibitor (ie tacrolimus or cyclosporine), those patients on high immunosuppressants containing high‐dose prednisone (>20 mg/day) or mammalian target of rapamycin (mTOR) inhibitor such as everolimus, 58 we recommend continuing NA prophylaxis beyond 1‐year post‐LT for this particular type of patient, because even 5%‐10% of HBV reactivation from HBcAb+ graft might carry significant morbidity in HBcAb+/HBsAb+ recipients. While mTOR inhibitor has immunosuppressive effects by blocking interleukin (IL)‐2 signalling, it also suppresses cellular immunity via affecting Th1‐cell function and inducing T‐cell growth, thereby controlling cellular immunity 59 .…”

Antiviral prophylaxis in patients with solid tumours and haematological malignancies—update of the Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO)

“…There are a growing number of reports on increased rates of opportunistic infections under this treatment [ 69 ]. However, in the COMFORT II trial, which compared the efficacy of ruxolitinib with the best available treatment in patients with myelfibrosis, the incidence of infections decreased over time without focus on reactivation of viral infections [ 70 ].…”