https://www.gastrojournal.org/article/S0016-5085(03)01518-X/pdf

Early is superior to deferred preemptive lamivudine therapy for hepatitis B patients undergoing chemotherapy

https://www.gastrojournal.org/article/S0016-5085(01)83909-3/pdf

Acute flares in chronic hepatitis B: the natural and unnatural history of an immunologically mediated liver disease.

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.

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

In places where hepatitis B virus (HBV) infection is endemic, it is often necessary to give chemotherapy to or perform bone marrow transplantation for cancer patients who are also chronic HBV carriers. When standard chemotherapy was given to lymphoma patients, elevation of liver transaminases was observed in nearly half of those who were chronic HBV carriers. Ten percent of them became jaundiced, and the overall liver-related mortality was about 5%. There is currently no reliable way to predict the severity of HBV reactivation after chemotherapy. The risk is probably higher when the chemotherapy used is significantly immunosuppressive and the viral load in the liver is high. Different strategies have been used in an attempt to reduce the risk of HBV reactivation after chemotherapy, but they have not been very successful. Further studies will be required to determine the impact of newly available antiviral agents that are active against HBV. Recipients who are carriers of HBV or who receive hepatitis B surface antigen (HBsAg)-positive marrow are at increased risk of hepatitis B-related morbidity and mortality after bone marrow transplantation (BMT). There is evidence to suggest that prophylactic use of an active antiviral agent, such as famciclovir, may result in a significant decrease in the incidence and severity of HBV reactivation after BMT. Sustained serologic clearance of chronic HBV infection has also been reported in many HBsAg-positive marrow recipients receiving hepatitis B surface antibody-positive marrow from their allogeneic donors. There seems to be a transfer of both humoral and cellular immunity against HBV from donors to recipients. Further prospective studies are required to define the best approach to manage HBsAg-positive cancer patients receiving chemotherapy or BMT. It is recommended that all cancer patients be checked for their hepatitis B status before receiving chemotherapy or a bone marrow transplant, especially if they reside in or come from endemic areas of HBV infection.

Chemotherapy and Bone Marrow Transplantation for Cancer Patients Who Are Also Chronic Hepatitis B Carriers: A Review of the Problem

How I treat and monitor viral hepatitis B infection in patients receiving intensive immunosuppressive therapies or undergoing hematopoietic stem cell transplantation

Use of famciclovir to prevent HBV reactivation in HBsAg-positive recipients after allogeneic bone marrow transplantation.

Background: Serological clearance of hepatitis B surface antigen (HBsAg) has been described after reception of hepatitis B surface antibody positive marrow, via allogeneic bone marrow transplantation (BMT). Histological changes during the clearance of HBsAg are unknown. Methods and Results: We described two chronic hepatitis B carriers (both hepatitis B e antigen negative), who cleared HBsAg after allogeneic bone marrow transplantation. Both received hepatitis B surface and core antibody positive human leucocyte antigen identical donors' marrow and had serological clearance of HBsAg 15 and 7 weeks after allogeneic BMT, respectively. Both events were preceded by hepatic flare. Both patients were also treated with famciclovir for the prevention of hepatitis B reactivation after BMT. Histological examination during the flare showed only mild necroinflammatory activity with multiple foci of confluent necrosis, associated with moderate lymphocytic infiltration. The majority of these lymphocytes were cluster of differentiation (CD) 8 positive. Using immunohistochemistry, there was no detectable hepatic expression of hepatitis B core antigen. However, HBsAg was positive, mainly in the area of confluent necrosis. Using in situ hybridization, hepatitis B virus (HBV) DNA was detected in the nucleus of 5% of hepatocytes, but not in the cytoplasm. Conclusions: At their last follow up, 22 and 16 months after BMT, the serum of both patients remained HBsAg negative, hepatitis B surface antibody positive and HBV-DNA negative by branched DNA assay.

CASE REPORT: Histological changes during clearance of chronic hepatitis B virus infection by adoptive immunity transfer

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Use of famciclovir to prevent HBV reactivation in HBsAg-positive recipients after allogeneic bone marrow transplantation.

CASE REPORT: Histological changes during clearance of chronic hepatitis B virus infection by adoptive immunity transfer