Hepatitis B virus reactivation in patients receiving chemotherapy for malignancies: role of precore stop‐codon and basic core promoter mutations

Summary.  Hepatitis B virus (HBV) strains carrying the precore stop‐codon mutation (A1896) have been considered among the predisposing factors for reactivation during chemotherapy for malignancies. The role of the T1762/A1764 basic core promoter (BCP) mutations has not been fully evaluated. We aimed to record any changes in HBV serological markers after reactivation, detect the presence of A1896 and BCP mutations and evaluate the type of cytotoxic drugs involved. We retrospectively screened eight patients presenting with HBV reactivation following chemotherapy for malignancies. The chemotherapy regimens used included corticosteroids (CSs), fludarabine and cyclophosphamide/adriamycine. The INNO‐LiPA HBV PreCore kit was used for the detection of the A1896 and BCP mutations. Six patients who were hepatitis B surface antigen (HBsAg)‐(+)/hepatitis B e antigen (HBeAg)‐(−) before chemotherapy, had disease reactivation following a mean of four cycles of chemotherapy. Four survived and two died of hepatic failure. At the time of reactivation, all six patients carried the A1896 and five of them the BCP mutations. The remaining two patients were HBsAg‐(−)/anti‐HBs‐(+)/anti‐hepatitis B core (HBc)‐(+)/HBeAg‐(−) before chemotherapy. One of them reverted to HBeAg‐(+) status but remained HBsAg‐(−), while the other became HBsAg‐(+)/HBeAg‐(+), following three and eight cycles of fludarabine treatment, respectively. The former carried the A1896 and the latter the wild‐type virus. Both died from causes associated with their haematological disease. All but one of our patients with HBV reactivation during chemotherapy carried the precore stop‐codon and BCP mutations. Whether this occurs more frequently in such patients than those carrying the wild‐type virus needs further investigation. Fludarabine should be added to the list of drugs inducing HBV reactivation. HBV reactivation following fludarabine treatment occurred in HBsAg‐(−) patients who had been anti‐HBs‐(+).