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Reactivation of hepatitis B virus infection in patients with hematologic disorders
Ferrata Storti Foundation
Haematologica 2019 Volume 104(3):435-443
Bo Wang,1 Ghulam Mufti2 and Kosh Agarwal1
1Institute of Liver Studies and 2Department of Hematology, King's College Hospital, London, UK
ABSTRACT
Hepatitis B reactivation is the reappearance or rise of hepatitis B virus (HBV) DNA in patients with past or chronic HBV infection, usually occurring in the context of immunosuppression. HBV reac- tivation has been most commonly reported in patients with hematologic disorders, with potentially serious and life-threatening consequences. In this review, we discuss the basis and presentation of HBV reactivation, and risk factors in terms of the host, the virus and the immunosuppression regimen, including newer agents used to manage hematologic malignan- cies. We overview the management of HBV reactivation, highlighting an up-dated recommendation on the use of newer nucleoside and nucleotide analogs, such as tenofovir and entecavir, for antiviral prophylaxis.
Introduction
Hepatitis B reactivation is the reappearance or rise of hepatitis B virus (HBV) DNA in the serum of patients with past or chronic HBV infection. Reactivation can occur in a variety of clinical settings, usually in the context of an immunosuppressed state or immunosuppressive therapy. HBV reactivation has been most commonly reported in patients receiving chemotherapy for hematologic malignancies and following hematopoietic stem cell transplants.1 An estimated 2 billion people worldwide have serological evidence of either past or present HBV infection, with around 240 million people chronically infected.2 The prevalence varies globally, ranging between 2% in Europe to over 10% in East Asia; in the UK it is estimated to be between 0.5-1.7%, with areas of greater ethnic diversity such as London having a higher prevalence of approximately 2.4%.2,3 Therefore, there is a clear potential for HBV reactivation to cause significant morbidity, and even mortality, if not appropriately diagnosed and managed.
Management of HBV in general is undergoing a paradigm shift. Recently up-dated clinical practice guidelines from the European Association for the Study of the Liver (EASL) have redefined the natural history of chronic HBV, driven by a better under- standing of the interactions between the virus and the host immune system.4 From a therapeutic point of view, existing agents effectively suppress virus replication and lower serum HBV DNA concentrations, but the goal now is to develop novel agents that can offer functional cure of HBV.5,6 This is defined as the loss of hepatitis B sur- face antigen (HBsAg), the hallmark of chronic infection. Complete sterilizing cure is not considered possible due to the persistence of HBV DNA within hepatocytes. However, if functional cure becomes a realistic treatment end point, the number of patients with resolved HBV infection but who remain at risk of reactivation may increase significantly.
Previous guidelines have been heterogeneous in their recommendations for the assessment of HBV reactivation, especially with regards to patient selection for test- ing and choice of antiviral prophylaxis. In this review, we aim to provide a practical overview of HBV reactivation at a time when the management of HBV is changing and the therapeutic options are expanding for patients with hematologic disorders, who are at the highest risk of this potentially life-threatening complication.
Hepatitis B virus reactivation and clinical presentation
Chronic HBV infection is defined by the presence of HBsAg in serum with vari-
Correspondence:
BO WANG
bo.wang@nhs.net
Received: November 22, 2018. Accepted: January 18, 2019. Pre-published: February 7, 2019.
doi:10.3324/haematol.2018.210252
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/3/435
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