title: Hepatitis B virus reactivation in patients undergoing cytotoxic chemotherapy for solid tumours: precore/core mutations may play an important role.
abstract: Reactivation of the hepatitis B virus (HBV) is a rare, but well described complication of cytotoxic chemotherapy that may result in hepatic failure. Patients who are chronic carriers of the HBV and who have a G to A mutation at nucleotide 1896 in the precore region may develop more severe liver disease, possibly because of rapid selection and enhanced replication ability of the mutant strain. Such mutant viruses have been implicated occasionally in chemotherapy induced reactivation of hepatitis B virus. In this report, 5 patients with solid tumours were identified to have developed severe hepatitis B virus related liver disease during treatment with cytotoxic agents (with dexamethasone as anti-emetic). All had clinical and serological evidence of reactivation of the HBV. Three patients developed icteric hepatitis; 2 fully recovered, and 1 had died from progressive metastatic disease while recovering from the reactivation. The other two died from progressive liver failure. Direct sequencing of the polymerase chain reaction (PCR) products of the precore (preC) and precore promoter region of the HBV-DNA was carried out on the patients' serum samples taken during the episode of reactivation. In each case, similar mutations (G to A) in nucleotide 1896 of the preC region were found, together with additional mutations in the preC promoter. The present findings suggest that reactivation involving a mutant hepatitis B virus may lead to liver failure, which is possibly more severe than that caused by wild type HBV, and can be triggered by cytotoxic chemotherapy, or the administration of corticosteroids. In Eastern Asia the HBV carriage rate in adults is high. HBV reactivation and severe liver disease during cytotoxic treatment may become a serious and common problem in this region as cytotoxic chemotherapy is more widely used. Patients should be screened routinely for HBsAg in endemic areas of chronic hepatitis B virus infection prior to receiving cytotoxic treatment. The possibility of HBV reactivation should be considered in patients developing liver dysfunction. Patients who are HBeAg negative/Anti-HBe positive, and are suspected to be having an HBV reactivation, should have HBV-DNA levels measured for confirmation as they may carry a mutant HBV.
authors.affiliation: Department of Clinical Oncology, Sir Y.K. Pao Centre for Cancer, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
authors.forename: J L
authors.initials: JL
authors.lastname: Steinberg
authors.forename: W
authors.initials: W
authors.lastname: Yeo
authors.forename: S
authors.initials: S
authors.lastname: Zhong
authors.forename: J Y
authors.initials: JY
authors.lastname: Chan
authors.forename: J S
authors.initials: JS
authors.lastname: Tam
authors.forename: P K
authors.initials: PK
authors.lastname: Chan
authors.forename: N W
authors.initials: NW
authors.lastname: Leung
authors.forename: P J
authors.initials: PJ
authors.lastname: Johnson
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001483:Base Sequence; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy*; D018288:Carcinoma, Small Cell / Q000150:complications / Q000188:drug therapy*; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D005260:Female; D018237:Germinoma / Q000150:complications / Q000188:drug therapy*; D006509:Hepatitis B / Q000821:virology*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D011401:Promoter Regions, Genetic; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D015534:Trans-Activators / Q000235:genetics; D054334:Viral Regulatory and Accessory Proteins; D014775:Virus Activation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D004279:DNA, Viral; D018894:Reverse Transcriptase Inhibitors; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D019259:Lamivudine