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      HBV Reactivation in Patients Undergoing Hematopoietic Stem Cell Transplantation: A Narrative Review

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          Abstract

          HBV reactivation (HBVr) can occur due to the ability of HBV to remain latent in the liver as covalently closed circular DNA and by the capacity of HBV to alter the immune system of the infected individuals. HBVr can occur in patients undergoing hematopoietic stem cell transplantation (HSCT) with a clinical spectrum that ranges from asymptomatic infection to fulminant hepatic failure. The risk of HBVr is determined by a complex interplay between host immunity, virus factors, and immunosuppression related to HSCT. All individuals who undergo HSCT should be screened for HBV. HSCT patients positive for HBsAg and also those HBcAb-positive/HBsAg-negative are at high risk of HBV reactivation (HBVr) due to profound and prolonged immunosuppression. Antiviral prophylaxis prevents HBVr, decreases HBVr-related morbidity and mortality in patients with chronic or previous HBV. The optimal duration of antiviral prophylaxis remains to be elucidated. The vaccination of HBV-naïve recipients and their donors against HBV prior to HSCT has an important role in the prevention of acquired HBV infection. This narrative review provides a comprehensive update on the current concepts, risk factors, molecular mechanisms, prevention, and management of HBVr in HSCT.

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          Most cited references99

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          Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus

          Human hepatitis B virus (HBV) infection and HBV-related diseases remain a major public health problem. Individuals coinfected with its satellite hepatitis D virus (HDV) have more severe disease. Cellular entry of both viruses is mediated by HBV envelope proteins. The pre-S1 domain of the large envelope protein is a key determinant for receptor(s) binding. However, the identity of the receptor(s) is unknown. Here, by using near zero distance photo-cross-linking and tandem affinity purification, we revealed that the receptor-binding region of pre-S1 specifically interacts with sodium taurocholate cotransporting polypeptide (NTCP), a multiple transmembrane transporter predominantly expressed in the liver. Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP expression rendered nonsusceptible hepatocarcinoma cells susceptible to these viral infections. Moreover, replacing amino acids 157–165 of nonfunctional monkey NTCP with the human counterpart conferred its ability in supporting both viral infections. Our results demonstrate that NTCP is a functional receptor for HBV and HDV. DOI: http://dx.doi.org/10.7554/eLife.00049.001
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            A global scientific strategy to cure hepatitis B

            Chronic hepatitis B virus (HBV) infection is a global public health challenge on the same scale as tuberculosis, HIV, and malaria. The International Coalition to Eliminate HBV (ICE-HBV) is a coalition of experts dedicated to accelerating the discovery of a cure for chronic hepatitis B. Following extensive consultation with more than 50 scientists from across the globe, as well as key stakeholders including people affected by HBV, we have identified gaps in our current knowledge and new strategies and tools that are required to achieve HBV cure. We believe that research must focus on the discovery of interventional strategies that will permanently reduce the number of productively infected cells or permanently silence the covalently closed circular DNA in those cells, and that will stimulate HBV-specific host immune responses which mimic spontaneous resolution of HBV infection. There is also a pressing need for the establishment of repositories of standardised HBV reagents and protocols that can be accessed by all HBV researchers throughout the world. The HBV cure research agenda outlined in this position paper will contribute markedly to the goal of eliminating HBV infection worldwide.
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              American Gastroenterological Association Institute guideline on the prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy.

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                Author and article information

                Journal
                Viruses
                Viruses
                viruses
                Viruses
                MDPI
                1999-4915
                10 November 2019
                November 2019
                : 11
                : 11
                : 1049
                Affiliations
                [1 ]Dept. Translational and Precision Medicine, Sapienza University of Rome, 00161 Rome, Italy
                [2 ]Dept. Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy
                Author notes
                Author information
                https://orcid.org/0000-0002-1105-5256
                https://orcid.org/0000-0002-2533-2939
                Article
                viruses-11-01049
                10.3390/v11111049
                6893755
                31717647
                5d1938b4-4381-4e9c-8eee-0be9ff5ff8c5
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 06 October 2019
                : 07 November 2019
                Categories
                Review

                Microbiology & Virology
                hbv reactivation,hepatitis b virus,hematopoietic stem transplantation,hsct,hbv,chronic hbv infection,resolved hbv infection,occult hbv infection,immune escape

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