Hepatitis B virus reactivation in patients undergoing cytotoxic chemotherapy for solid tumours: Precore/core mutations may play an important role

Reactivation of the hepatitis B virus (HBV) is a rare, but well described c omplication of cytotoxic chemotherapy that may result in hepatic failure. P atients who are chronic carriers of the HBV and who have a G to A mutation at nucleotide 1896 in the precore region may develop mote severe liver dise ase, possibly because of rapid selection and enhanced replication ability o f 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 hepa titis B virus related liver disease during treatment with cytotoxic agents (with dexamethasone as antiemetic). All had clinical and serological eviden ce 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 live r failure. Direct sequencing of the polymerase chain reaction (PCR) product s of the precore (preC) and precore promoter region of the HBV-DNA was carr ied out on the patients' serum samples taken during the episode of reactiva tion. In each case, similar mutations (G to A) in nucleotide 1896 of the pr eC region were found, together with additional mutations in the preC promot er. The present findings suggest that reactivation involving a mutant hepat itis 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 chemotherap y, or the administration of corticosteroids. In Eastern Asia the HBV carria ge 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 infectio n prior to receiving cytotoxic treatment. The possibility of HBV reactivati on 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. J. Med. Virol. 60: 249-255, 2000, (C) 2000 Wil ey-Liss, Inc.