title: Prophylaxis against chemotherapy-induced reactivation of hepatitis B virus infection with Lamivudine.
abstract: The results of lamivudine therapy in 4 patients with chemotherapy-induced hepatitis B virus (HBV) reactivation are reported. Cancer chemotherapy-induced reactivation is a known complication in patients with chronic HBV infection or history of HBV infection with recovery. Reactivation of HBV infection has a broad spectrum of manifestations ranging from mild elevation of aminotransferase levels to fatal fulminant hepatitis. Lamivudine is a nucleoside analogue and a potent inhibitor of HBV reverse transcription. The 4 patients treated with lamivudine included 1 woman with breast cancer and 3 men with non-Hodgkin lymphoma, ranging from 41 to 63 years of age. All 4 patients were undergoing standard, multi-agent chemotherapy when they presented with HBV reactivation manifested by sudden onset of fatigue, jaundice, and HBV serology consistent with active HBV infection (detectable serum HBV DNA) in the absence of other known causes of acute hepatitis. Lamivudine therapy (100 mg/d in 3 patients and 150 mg/d in 1 patient) was initiated from 1 to 18 days following the diagnosis of HBV reactivation. All 4 patients showed rapid decrease in aminotransferase levels within 2 weeks after initiating lamivudine therapy. Unfortunately, hepatic synthetic function failed to improve in 2 patients, who both died. The remaining 2 patients had suppression of HBV DNA to undetectable levels after 1 and 4 months of treatment and had biochemical and clinical improvement. The 2 patients who died received lamivudine therapy for 8 days and for 3 weeks. There have been no randomized clinical trials to study the role of lamivudine for prophylaxis or treatment of HBV reactivation associated with chemotherapy. However, based on our limited experience, lamivudine may be efficacious in suppressing potentially fatal HBV reactivation secondary to chemotherapy in patients with chronic HBV infection or prior infection with recovery. Patients who undergo chemotherapy should be screened for the presence of markers of chronic hepatitis B infection or previous HBV infection. We recommend that patients with chronic HBV infection (positive HBV DNA and/or positive HBsAg) or history of HBV infection with recovery (positive hepatitis B core antibody with or without HBsAb) be considered for prophylactic lamivudine use to prevent chemotherapy-induced HBV reactivation.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California 94304, USA.
authors.forename: Nicole D
authors.initials: ND
authors.lastname: Simpson
authors.forename: Peter W
authors.initials: PW
authors.lastname: Simpson
authors.forename: Ali M
authors.initials: AM
authors.lastname: Ahmed
authors.forename: Mindie H
authors.initials: MH
authors.lastname: Nguyen
authors.forename: Gabriel
authors.initials: G
authors.lastname: Garcia
authors.forename: Emmet B
authors.initials: EB
authors.lastname: Keeffe
authors.forename: Aijaz
authors.initials: A
authors.lastname: Ahmed
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006509:Hepatitis B / Q000188:drug therapy / Q000517:prevention & control*; D006515:Hepatitis B virus / Q000187:drug effects / Q000254:growth & development*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000821:virology; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects; D014775:Virus Activation / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone