Hepatitis B Virus Reactivation in the Setting of Cancer Chemotherapy and Other Immunosuppressive Drug Therapy

Abstract

Hepatitis B virus reactivation (HBVr) is an important complication of immunosuppressive drug therapy (ISDT). It can occur with active or resolved hepatitis B virus (HBV) infection with a clinical spectrum that ranges from mild elevations in liver tests to fulminant hepatic failure. The risk of it occurring is determined by the interplay between HBV serological status, level of viremia, and the immunosuppressive potency of the drug(s) used. Reactivation is most common during treatment of hematologic malignancies but also occurs with chemotherapy for breast cancer and numerous other solid organ malignancies, organ transplant, and immune suppression for nonmalignant conditions. The expansion of new biologic treatments for malignant and nonmalignant disorders has enlarged the population at risk. Increased awareness of HBVr among healthcare providers who prescribe ISDT, adoption of routine HBV screening, and linking the results of screening to antiviral prophylaxis are needed to reduce the incidence of this potentially fatal but preventable disorder.

Keywords: HBVr; ISDT; cancer; chemotherapy; liver.

Figure 1.

Hepatitis B virus (HBV) reactivation (HBVr) risk based on potency of immunosuppressive drug therapy and degree of host immune control. The risk of HBVr occurs along a continuum influenced by host immune control of viral replication. This is reflected by serological status and/or the presence and level of HBV DNA. HBVr risk also increases in relation to the potency of the administered immunosuppressive drugs. In this graph, it is assumed that all patients with antibody to hepatitis B surface antigen are positive for antibody to hepatitis B core antigen. Abbreviations: anti-HBs, antibody to hepatitis B surface antigen; HBsAg, hepatitis B surface antigen.

Figure 2.

Prospective randomized controlled trials evaluating antiviral prophylaxis for hepatitis B virus (HBV) reactivation are shown involving a range of malignancies and mostly individuals positive for hepatitis B surface antigen [, , –43]. Studies compared nucleoside analogue prophylaxis vs deferred approach (controls) or lamivudine vs entecavir. The higher frequency of HBV reactivation in lamivudine-treated patients on the right side of the figure most likely reflects the use of more aggressive immunosuppression in the studies by Kim [13] and Huang [43] . Rituximab was a component of chemotherapy in these 2 studies but was not incorporated into the treatment regimens on the left side of the graph. Abbreviations: HBsAg, hepatitis B surface antigen; HCC, hepatocellular carcinoma; NS, not significant; TACE, transarterial chemoembolization.

Figure 3.

Management algorithm for patients requiring immunosuppressive drug therapy. The initial screening with hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBc) leads to identification of 3 groups of patients. All susceptible individuals should be considered for vaccination. Those with resolved hepatitis B (HBsAg negative, anti-HBc positive) should be checked for hepatitis B virus (HBV) DNA if given intermediate- to high-risk immunosuppressive drug therapy (ISDT) (see text and [1] for drug classification according to degree of risk). All HBsAg-positive patients should have HBV DNA testing and antiviral prophylaxis. Patients positive for anti-HBc for whom deferred therapy is chosen should undergo regular HBV DNA and alanine aminotransferase (ALT) testing if given treatment with intermediate-risk ISDT. Such patients can undergo regular ALT monitoring with reflex HBV DNA testing if given low-risk ISDT. Low-resistance antivirals such as entecavir or tenofovir are preferred for prophylaxis and in the event that HBV reactivation occurs.