Reactivation of Hepatitis B Virus in Patients Receiving Chemotherapy

Abstract

In patients undergoing chemotherapy for the treatment of malignant disease, the reactivation of hepatitis B virus in hepatitis B surface antigen-positive patients has been frequently reported. However, activation has also been reported in hepatitis B surface antigen-negative patients who test positive for hepatitis B core antibody and/or hepatitis B surface antibody, who were thought to have had transient infections and to have been cured. Reactivation has often been reported in patients receiving rituximab-containing regimens and has attracted a lot of attention in recent years. In Japan, 1 -3% of patients undergoing chemotherapy are hepatitis B surface antigen-positive, and 20 -25% of patients are hepatitis B surface antigen-negative with hepatitis B core antibody and/or hepatitis B surface antibody positivity; therefore, about one out of every four patients undergoing chemotherapy may be at risk for the reactivation of hepatitis B virus. In most of the guidelines for hepatitis B virus reactivation, the prophylactic administration of an antiviral drug in hepatitis B surface antigen-positive patients is recommended, and periodic monitoring of hepatitis B virus DNA and the deferred pre-emptive administration of an antiviral drug after conversion to hepatitis B virus DNA positivity are recommended in hepatitis B surface antigen-negative patients who are hepatitis B core antibody-positive and/or hepatitis B surface antibody-positive when chemotherapy has been scheduled. However, numerous issues regarding hepatitis B virus reactivation, including the frequency, the types of anticancer drugs, the cancers that facilitate hepatitis B virus reactivation and the optimal method of management, etc., have not been fully clarified. A variety of well-designed prospective studies are currently under way in both Japan and abroad, and strong evidence of hepatitis B virus reactivation following chemotherapy is anticipated in the future.

Follow-up of the Chronic HBV Infected Patients Planned Chemotherapy Due to Solid Organ Malignancy

“…4 In the literature, there are studies reporting HBV reactivation in patients who received anthracyclines, alkylating agents, fluorouracil, docetaxel or epirubicin in their chemotherapy regimen. [26][27][28] In our study, HBV reactivation developed in patients who received cisplatin, docetaxel, or cyclophosphamide in their chemotherapy regimens and therefore we suggest that such patients should be monitored more closely.…”

Hepatitis B Reactivation in Immunosupressed Patients, Prophylaxis and Management

“…[2] 3 with HBsAg-negative and HBcAg-positive, hepatitis B virus reactivation is characterized by reappearance of HBsAg with the increase of ALT level in two measurements over a period of 5 days, and increase of hepatitis B virus DNA more than 10 5 copies/mL. 4,5,6 Hepatitis B reactivation has been described as a three-phase event (Figure 1). Initially, an increased HBV DNA levels in an HBsAg positive person is found, or reappearance of either HBsAg (seroconversion) or HBV DNA occurs; this period is usually asymptomatic.…”

“…IS: Immunosuppression; HBV: Hepatitis B virus; ALT: Alanine aminotransferase; HBsAg: Hepatitis B surface Antigen [2] B virus reactivation during anticancer treatment may results in life-threatening events and poor outcome due to early discontinuation of chemotherapy. 6,8 The first prospective study on hepatitis B virus reactivation was published in 1991, and included Chinese patients with malignant lymphoma who received chemotherapy. Hoofnagle et al described 2 cases of hepatitis B virus reactivation in asymptomatic hepatitis B virus carriers within 3 months of starting chemotherapy.…”

Association of Chronic HBV Infection with Chronic Lymphoproliferative Disorders: A Review and Case Report

“…Thus, it became evident that reactivation as a result of the combined use of chemotherapy with a high immunosuppressive effect, such as rituximab, or combination therapy with a steroid can occur even in HBsAg-negative patients with HBcAb and/or HBsAb positivity. [16] The number of reports regarding HBV reactivation following chemotherapy has been gradually increasing. Guidelines for the treatment of HBV reactivation following chemotherapy have been published by many groups: the American Association for the Study of Liver Disease (AASLD) Practice Guidelines in 2007; [17] the National Institute of Health (NIH) Consensus Development Conference Management of Hepatitis B in 2008 [18,19] and the European Association for the Study of the Liver (EASL) Clinical Practice Guidelines in 2009.…”

“…[25] Once administration has been continued for 12 months after the completion of chemotherapy and a decrease in the ALT level to within the normal range and conversion to persistent HBV-DNA negativity have been achieved, the termination of the administration of the antiviral drug can be considered . [16,26] Castleman's disease, also known as angiofollicular lymph node hyperplasia, is characterized by non-clonal lymph node proliferation, and was first described by Benjamin Castleman in 1954. [27] Pathologically, it is classified into three types: hyaline-vascular (HV), plasma-cell (PC) and mixed type.…”