HBV reactivation after fludarabine chemotherapy identified on investigation of suspected transfusion-transmitted Hepatitis B virus.
OBJECTIVE
Multi-transfused patients often receive treatments inducing various levels of immunodeficiency. Acute viral infections may then be attributed either to transfusion-transmitted infection (TTI) or reactivation of a past infection.


METHODS
A patient with chronic lymphocytic leukemia (CLL) who had >250 blood donor exposures developed acute Hepatitis B virus (HBV) infection. Routine donor testing for HB core antibodies (anti-HBc) was in place in the relevant period and investigations undertaken on the blood donors were negative.


RESULTS
Review of historical, molecular, and antigenic evidence demonstrated reactivation of a recovered HBV infection dating >30 years and the selection of a rare escape mutant that briefly replicated and caused acute liver disease. This mutant was unreactive with several HBsAg assays and poorly reactive with an HBV vaccine plasma. Correcting the C139Y substitution by site directed mutagenesis of recombinant surface proteins re-established assay reactivity.


CONCLUSIONS
Fludarabine, but not Chlorambucil, appeared sufficiently immunosuppressive to trigger reactivation despite low levels of neutralizing antibodies. Differentiating between TTI and reactivation of HBV becomes more challenging with the increasing frequency of immunocompromised blood recipients. Chemotherapy with Fludarabine alone should be considered as carrying high risk of viral reactivation. Pre-treatment testing and peripheral blood sample archiving may be indicated in HBsAg negative patients.
Power
J P
JP
Munster Regional Transfusion Centre, Irish Blood Transfusion Service, St. Finbarr's Hospital, Cork, Ireland.
El Chaar
M
M
Temple
J
J
Thomas
M
M
Spillane
D
D
Candotti
D
D
Allain
J P
JP
D000970:Antineoplastic Agents / Q000009:adverse effects*; D001803:Blood Transfusion; D018562:Disease Transmission, Infectious; D006509:Hepatitis B / Q000209:etiology* / Q000821:virology; D006515:Hepatitis B virus / Q000302:isolation & purification*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D014740:Vidarabine / Q000009:adverse effects / Q000031:analogs & derivatives*; D014775:Virus Activation / Q000187:drug effects*
D000970:Antineoplastic Agents; D014740:Vidarabine; C024352:fludarabine