Hepatitis B virus reactivation in breast cancer patients receiving cytotoxic chemotherapy: A prospective study

Abstract

Breast cancer is a rapidly increasing problem in many developing countries, and cytotoxic chemotherapy is now an integral part of its management. In several developing countries, the carriage of hepatitis B virus (HBV) in cancer patients may be as high as 12%, and such patients are at risk of developing fatal HBV reactivation during chemotherapy. HBV reactivation is well recognized in patients with hematological malignancies, but limited data are available on patients with other, more common, cancers, such as breast cancer. Recent data have suggested that increased viral replication, an indication of HBV reactivation, may precede clinical hepatitis. In the absence of serial HBV DNA monitoring, HBV reactivation during chemotherapy may have been underestimated. In this prospective study, breast cancer patients who were hepatitis B surface antigen (HBsAg) seropositive were followed up during chemotherapy. The main objectives were to determine the incidence of HBV reactivation in breast cancer patients undergoing conventional chemotherapy; to investigate whether “serial HBV DNA monitoring” improves the accuracy of diagnosing HBV reactivation when compared with previous schema that only measured HBV DNA at the time of clinical hepatitis (“conventional monitoring”); and to assess the clinical consequences as a result of developing the condition. The secondary objective was to identify risk factors associated with this condition. Over an 18‐month period, 41 patients were studied. Ten developed HBV reactivation by conventional monitoring criteria, but with serial HBV DNA monitoring, seven additional patients were diagnosed when increased HBV DNA levels were detected before, but not concomitant with, clinical hepatitis. Thus, a total of 17 patients (41%) developed HBV reactivation. Premature termination of chemotherapy or delay in treatment schedules occurred in 71% of the patients who developed viral reactivation, as compared with 33% in those who did not develop the condition (P = 0.019). No risk factors associated with the development of HBV reactivation could be identified. Serial monitoring of HBV DNA, in addition to liver function, increases the sensitivity of diagnosing of HBV reactivation, and helps explain some cases that would otherwise be labeled as “cryptogenic hepatitis,” for which concomitant HBV DNA measured at the time of hepatitis was undetectable. The present study highlights the importance of monitoring HBsAg‐seropositive patients who are receiving chemotherapy for common solid tumors such as breast cancer. J. Med. Virol. 70:553–561, 2003. © 2003 Wiley‐Liss, Inc.

Comprehensive analysis of risk factors associating with Hepatitis B virus (HBV) reactivation in cancer patients undergoing cytotoxic chemotherapy

“…In the present study, it is interesting to find that the use of steroids was an associated risk factor on multivariate analysis. Patients with lymphoma have more frequently been reported to develop HBV reactivation (Lok et al, 1991;Omata et al, 1991;Nokamura et al, 1996;Yeo et al, 2000a), and a recent report on breast cancer patients receiving chemotherapy has shown the viral reactivation rate to be as high as 41% (Yeo et al, 2003). The type of treatment and the type of tumour may be inter-related factors.…”

Hepatitis B reactivation after chemotherapy: two decades of clinical research

“…In the past, we saw patients who died of fulminant hepatic failure after being administered a few courses of cytotoxic therapy to treat their life-threatening lymphoma [6][7][8][9] and breast cancer [10][11][12] if they were also hepatitis B surface antigen positive. At that time, the literature report of this important clinical issue was scanty.…”

“…Almost all these patients had intense marrow suppression with a drastic reduction of white cell count, and the rebound of the white cell with immune recovery correlates with the initiation of liver damages [56]. Severe hepatitis due to HBV reactivation has also been reported in HBV-infected patients treated with chemotherapy for other malignancies such as breast cancer [10][11][12], hepatocellular carcinoma [18,57,58], small-cell lung cancer [59], and nasopharyngeal cancer [60]. The relative lack of report in other type of malignancy is probably related to their lower incidence in HBV endemic area, such as the Asia-Pacific region.…”

“…Also, not all patients could withstand percutaneous liver biopsy as they might have clotting derangement, especially those with hematological malignancy [83]. Another viral factor that has been investigated is hepatitis B e antigen (HBeAg) but the results are conflicting [6,10,58,89,[93][94][95]. This is probably related to the presence of the precore/core promoter HBV mutants (i.e., HBeAg-negative/hepatitis B e antigen-positive chronic hepatitis B infection) [96].…”

Prevention of acute exacerbation of chronic hepatitis B infection in cancer patients receiving chemotherapy in a hepatitis B virus endemic area

“…[5][6][7][8] Reactivation of HBV infection in cancer patients receiving chemotherapy may cause interruption of chemotherapy and, in severe cases, lead to liver failure and death. [9][10][11] Additionally, the prognosis of cancer may be compromised by disruption in anticancer treatment during the course of hepatitis, with a delay in treatment cycles and premature termination of chemotherapy. 4 Administering oral anti-HBV agents before chemotherapy is an effective means of reducing HBV reactivation and preventing fatal complications in patients with chronic HBV infection.…”