Review
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 28, 2016; 22(28): 6484-6500
Published online Jul 28, 2016. doi: 10.3748/wjg.v22.i28.6484
Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies treated with anticancer therapy
Man Fai Law, Rita Ho, Carmen KM Cheung, Lydia HP Tam, Karen Ma, Kent CY So, Bonaventure Ip, Jacqueline So, Jennifer Lai, Joyce Ng, Tommy HC Tam
Man Fai Law, Carmen KM Cheung, Lydia HP Tam, Karen Ma, Kent CY So, Bonaventure Ip, Jacqueline So, Jennifer Lai, Joyce Ng, Tommy HC Tam, Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong, China
Rita Ho, Department of Medicine, North District Hospital, Hong Kong, China
Author contributions: Law MF designed the research topic; all authors contributed to the literature search, analysis and writing the paper.
Conflict-of-interest statement: The authors declare no conflict of interest for this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Man Fai Law, Department of Medicine and Therapeutics, Prince of Wales Hospital, Shatin, Hong Kong, China. mflaw99@yahoo.com.hk
Telephone: +852-97763090
Received: April 1, 2016
Peer-review started: April 7, 2016
First decision: May 12, 2016
Revised: May 24, 2016
Accepted: June 15, 2016
Article in press: June 15, 2016
Published online: July 28, 2016
Processing time: 111 Days and 21.4 Hours
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.

Keywords: Hepatitis B virus reactivation; Hematological malignancies; Rituximab; Hematopoietic stem cell transplant; Prophylactic antiviral therapy

Core tip: Hepatitis due to hepatitis B virus (HBV) reactivation can be severe and potentially fatal. All patients with hematological malignancies receiving anticancer therapy should be screened for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen. Patients found to be positive for HBsAg should be given prophylactic antiviral therapy. For patients with resolved HBV infection, either pre-emptive therapy guided by serial HBV DNA monitoring or prophylactic antiviral therapy, especially for patients receiving high-risk therapy are reasonable options. Further studies are needed to find out the best prophylactic strategy in the era of targeted therapy for hematological malignancies.