Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies treated with anticancer therapy

Abstract

Hepatitis due to hepatitis B virus (HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBc). Patients found to be positive for HBsAg should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving high-risk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although there is currently limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBsAg-positive patients receiving novel treatments, especially the Bruton tyrosine kinase inhibitors and the phosphatidylinositol 3-kinase inhibitors, which are B-cell receptor signaling modulators and reduce proliferation of malignant B-cells. Further studies are needed to clarify the risk of HBV reactivation with these agents and the best prophylactic strategy in the era of targeted therapy for hematological malignancies.

Evaluation of hepatitis B reactivation among 62,920 veterans treated with oral hepatitis C antivirals

“…HBV reactivation in other clinical contexts is most commonly reported in the setting of immune suppression in patients receiving cancer chemotherapy, especially rituximab‐containing therapy for hematological malignancies and stem cell transplantation . No standard strategy has yet been established to prevent HBV reactivation; however, two options are often undertaken.…”

Hepatitis B virus screening frequency and real life data in immunosuppressive patients

“…[6] Güncel kılavuzlarda, HBV açısından naif hastalara, mümkünse tedaviden önce çift doz aı öner-mektedir. [5] Çalımamızda naif hastaların sıklı¤ı fazla olmakla birlikte bu hastaların aılamaya yön-lendirilme oranlarında ciddi düüklük saptandı.…”

“…[3][4][5] Özellikle T ve B lenfosit fonksiyonlarının baskılandı¤ı steroid, rituksimab kullanımı, kemik ili¤i nakli gibi durumlar HBV reaktivasyonu veya akut HBV enfeksiyonu açısından yüksek riskli olarak kabul edilmektedir. [6] Tüm hastalara, immünsüpresif tedavi öncesi HBsAg, hepatit B core protein antikoru (Anti-HBcIgG), hepatit B yüzey antijeninin antikoru (AntiHBs), hepatit C virus antikoru (AntiHCV) ve insan edinsel immün yetmezlik virüs antikoru (AntiHIV) taraması yapılması önerilmektedir. [6] Hepatit B açısından seronegatif hastalar, mümkünse tedavi öncesi aılamaya yönlendirilmelidir.…”

“…[6] Tüm hastalara, immünsüpresif tedavi öncesi HBsAg, hepatit B core protein antikoru (Anti-HBcIgG), hepatit B yüzey antijeninin antikoru (AntiHBs), hepatit C virus antikoru (AntiHCV) ve insan edinsel immün yetmezlik virüs antikoru (AntiHIV) taraması yapılması önerilmektedir. [6] Hepatit B açısından seronegatif hastalar, mümkünse tedavi öncesi aılamaya yönlendirilmelidir. [4,5,7] ‹mmünsüpresyon nedeni ile bu hastalar immün yanıt oluturabilmek için yüksek doz ve ek aı dozlarına ihtiyaç duyabilmektedir.…”

Prevention of hepatitis B virus reactivation in patients with hematological malignancies and resolved hepatitis B virus infection: a systematic review and meta‐analysis

“…The risk of reactivation depends on the underlying disease, types of treatment and host factors. HBV reactivation is a significant risk in patients who have a previous HBV infection and who require chemotherapy for hematological malignancies or are undergoing hematopoietic stem cell transplants (HSCT) . After the resolution of an acute HBV infection, small amounts of HBV DNA can remain in the liver, even if the DNA is no longer detectable in peripheral blood.…”