Hepatitis B Reactivation During Immunosuppressive Therapy or Cancer Chemotherapy, Management, and Prevention: A Comprehensive Review

Abstract

ContextDue to the close relationship between the immune system and the hepatitis B virus (HBV) replication, it is essential to monitor patients with current or past HBV infection under any type of immunosuppression. Cancer chemotherapy, immunosuppressive therapies in autoimmune diseases, and immunosuppression in solid organ and stem cell transplant recipients are the major reasons for hepatitis B virus reactivation (HBVr). In this review, the challenges associated with HBVr are discussed according to the latest studies and guidelines. We also discuss the role of treatments with different risks, including anti-CD20 agents, tumor necrosis factor-alpha (TNF-α) inhibitors, and other common immunosuppressive agents in various conditions.Evidence AcquisitionThrough an electronic search of the PubMed, Google Scholar, and Scopus databases, we selected the studies associated with HBVr in different conditions. The most recent recommendations were collected in order to reach a consensus on how to manage patients at risk of HBVr.ResultsIt was found that the positive hepatitis B surface antigen (HBsAg), the high baseline HBV DNA level, the positive hepatitis B virus e antigen (HBeAg), and an absent or low hepatitis B surface antibody (HBsAb) titer prior to starting treatment are the most important viral risk factors. Furthermore, rituximab, anthracycline, and different types of TNF-α inhibitors were identified as the high-risk therapies. By analyzing the efficiency of prophylaxis on the prevention of HBVr, it was concluded that those with a high risk of antiviral resistance should not be used in long-term immunosuppressants. Receiving HBV antiviral agents at the commencement of immunosuppressant therapy or chemotherapy was demonstrated to be effective in decreasing the risk of HBVr. Prophylaxis could also be initiated before the start of therapy. For most immune suppressive regimes, antiviral therapy should be kept up for at least 6 months after the cessation of immunosuppressive drugs. However, the optimal time of prophylaxis keeping should be increased in cases associated with rituximab or hematopoietic stem cell transplants. According to the latest studies and guidelines from different bodies, recommendations regarding screening, monitoring, and management of HBVr are outlined.ConclusionsIdentification of patients at the risk of HBVr before immunosuppressive therapy is an undeniable part of treatment. Starting the antiviral therapy, based on the type of immunosuppressive drugs and the underlying disease, could lead to better management of disease.

Comparison of Vitamin D Levels in Naive, Treated, and Inactive Carriers with Chronic Hepatitis B Virus

“…From the Th2 and Tregs promotion, which leads to decreased HBV-specific immune responses (IFN-γ and TNF-α), an elevation in viral load could occur. According to our previous studies, high levels of anti-HBV cytokines or low levels of these cytokines could lead to HBV flare and HBV reactivation, respectively 18,25. It seems that vitamin D3 contributes to prevention of HBV flare via a mechanism involving increase in Tregs population and promotion of their functions.…”

Management of chronic hepatitis B in special populations

“…There is high resistance to lamivudine (LAM) with a risk of reactivation following more than 6 months from the cessation of immunosuppressive therapy or chemotherapy. It is recommended that referenced HBV antiviral agents, such as entecavir (ETV) and TNV should be used in therapies that need long-term prophylaxis 24 .…”

Hepatitis B Reactivation Rate Is Higher Undergoing Some Cytotoxic Chemotherapy in Patients with Solid Tumors: A Large Retrospective Study

“…But there are many unanswered questions about HBV screening prior to chemotherapy for solid tumors and there is no sufficient evidence about which appropriate population to screen. Based on 3 major HBV treatment guidelines, all cancer patients should be checked for HBV markers prior to the initiation of chemotherapy and also guidelines from the international liver society recommended mandatory screening for serum HBsAg and anti-HBc before starting all forms of immunosuppression [15][16][17].…”