Doxorubicin activates hepatitis B virus (HBV) replication in HBV-harboring hepatoblastoma cells. A possible novel mechanism of HBV reactivation in HBV carriers receiving systemic chemotherapy.
BACKGROUND
Reactivation of HBV replication is a clinically significant complication in HBV(+) patients receiving chemotherapy. We recently found that nearly half of the HBV reactivation in lymphoma patients occurred within 2 weeks of the first dose of chemotherapy. We hypothesized that mechanisms other than immunosuppression, such as direct stimulation of HBV replication by anticancer drugs, might be involved in this type of HBV reactivation.


METHODS
2.2.15 cells, which secrete HBV particles constitutively, were used in the experiments. Real-time quantitative polymerase chain reaction was used to quantitate HBV DNA, and microparticle enzyme immunoassay to measure HBV surface antigen (HBsAg).


RESULTS
HBV DNA secretion in culture medium was dose- dependently increased by doxorubicin, one of the most commonly used anticancer drugs for lmphoma. One-hour exposure of cells to 1 microM doxorubicin induced a 15.4+/-5.9-fold and a 3.05+/-0.09-fold increase of HBV DNA and HBsAg on the 4th culture day, respectively. Lamivudine suppressed the doxorubicin-induced increase of HBV DNA.


CONCLUSIONS
Our data suggest that cytotoxic agents may stimulate the replication of HBVand thereby contribute to the reactivation of HBV during systemic chemotherapy. Importantly, this adverse effect of cytotoxic agents may be preventable by co-administration of lamivudine.
Hsu
Chih-Hung
CH
Department of Oncology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
Hsu
Hui-Chen
HC
Chen
Hui-Ling
HL
Gao
Ming
M
Yeh
Pei-Yen
PY
Chen
Pei-Jer
PJ
Cheng
Ann-Lii
AL
D000903:Antibiotics, Antineoplastic / Q000009:adverse effects; D045744:Cell Line, Tumor; D004279:DNA, Viral / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000009:adverse effects*; D006514:Hepatitis B Surface Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000150:complications / Q000821:virology; D018197:Hepatoblastoma / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D007700:Kinetics; D019259:Lamivudine / Q000494:pharmacology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000821:virology*; D016133:Polymerase Chain Reaction; D014775:Virus Activation / Q000187:drug effects*
D000903:Antibiotics, Antineoplastic; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D019259:Lamivudine; D004317:Doxorubicin