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      Poor Recognition of Risk Factors for Hepatitis B by Physicians Prescribing Immunosuppressive Therapy: A Call for Universal Rather than Risk-Based Screening

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          Abstract

          Background

          Reactivation of hepatitis B virus (HBV) during immunosuppressive therapy (IST) can lead to severe and even fatal hepatitis but can be largely prevented with prophylactic antiviral therapy. Screening for HBV prior to starting IST is recommended. Both risk-based and universal screening have been recommended by different societies. For effective risk-based screening, physicians must be aware of risk factors for chronic HBV infection.

          Methods

          The HBV screening practices prior to starting IST of rheumatologists, medical and hematological oncologists were evaluated by survey and chart review. Country of origin, the primary risk factor for HBV exposure, was determined in all patients.

          Results

          Of 140 rheumatology, 79 medical oncology and 53 hematology patients reviewed, 81%, 11% and 81% were deemed to be at high risk of HBV reactivation by their physicians respectively, however only 27%, 6% and 62% (p<0.0001) were actually screened for HBV prior to starting IST. For patients from HBV-endemic regions, more hematology patients (53%) were correctly identified by their physicians as being at high risk of reactivation than rheumatology patients (2.4%, p=0.0001) or medical oncology patients (15%, p=0.009). However actual screening rates were not increased in patients from endemic regions. A total of 81 patients were screened for HBsAg; 2 were positive. Of the 33 patients screened for anti-HBc, 10 (30%) were positive.

          Conclusions

          Hematologists, rheumatologists and medical oncologists had low rates of screening for HBV prior to prescribing IST, largely due to poor identification of those at risk for infection. Risk-based screening strategies are unlikely to be effective and should be replaced by universal screening.

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          Most cited references27

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          Chronic hepatitis B.

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            Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update

            Large amounts of new data on the natural history and treatment of chronic hepatitis B virus (HBV) infection have become available since 2005. These include long-term follow-up studies in large community-based cohorts or asymptomatic subjects with chronic HBV infection, further studies on the role of HBV genotype/naturally occurring HBV mutations, treatment of drug resistance and new therapies. In addition, Pegylated interferon α2a, entecavir and telbivudine have been approved globally. To update HBV management guidelines, relevant new data were reviewed and assessed by experts from the region, and the significance of the reported findings were discussed and debated. The earlier “Asian-Pacific consensus statement on the management of chronic hepatitis B” was revised accordingly. The key terms used in the statement were also defined. The new guidelines include general management, special indications for liver biopsy in patients with persistently normal alanine aminotransferase, time to start or stop drug therapy, choice of drug to initiate therapy, when and how to monitor the patients during and after stopping drug therapy. Recommendations on the therapy of patients in special circumstances, including women in childbearing age, patients with antiviral drug resistance, concurrent viral infection, hepatic decompensation, patients receiving immune-suppressive medications or chemotherapy and patients in the setting of liver transplantation, are also included.
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              Reactivation of hepatitis B.

              Reactivation of hepatitis B refers to the abrupt increase in hepatitis B virus (HBV) replication in a patient with inactive or resolved hepatitis B. Reactivation can occur spontaneously, but more typically is triggered by immunosuppressive therapy of cancer, autoimmune disease, or organ transplantation. Reactivation can be transient and clinically silent, but often causes a flare of disease that can be severe resulting in acute hepatic failure. Most instances of reactivation resolve spontaneously, but if immune suppression is continued, re-establishment of chronic hepatitis occurs which can lead to progressive liver injury and cirrhosis. The best-described instances of reactivation occur in hepatitis B surface antigen (HBsAg) carriers with inactive or minimally active disease who are given cancer chemotherapy for lymphoma or leukemia. Typically, serum HBV DNA rises during chemotherapy, followed by a disease flare and HBV DNA clearance with immune reconstitution after chemotherapy is stopped. Special forms of reactivation occur after solid organ and bone marrow transplantation in which chronic infection often results. Several randomized, placebo-controlled trials have shown that reactivation can be prevented by antiviral prophylaxis. Routine prophylaxis is therefore recommended for persons with HBsAg undergoing cancer chemotherapy or transplantation, but major questions remain. Which patients should be screened for HBsAg and should all be treated? Which antiviral should be used and for how long? Should persons with resolved hepatitis B without HBsAg receive prophylaxis? Future research should address the underlying molecular mechanisms of reactivation as well as its optimal means of diagnosis, treatment, and prevention in different patient populations.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                15 April 2015
                2015
                : 10
                : 4
                : e0120749
                Affiliations
                [1 ]Toronto Centre for Liver Disease, University Health Network, University of Toronto, Toronto, Canada
                [2 ]St. Michael’s Hospital, University of Toronto, Toronto, Canada
                [3 ]Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Canada
                [4 ]University Health Network, Toronto, Canada
                CRCL-INSERM, FRANCE
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: AV KKWC LKH JJF. Performed the experiments: AV JB PM. Analyzed the data: AV LKH JJF. Contributed reagents/materials/analysis tools: AV KKWC JJF. Wrote the paper: AV LKH JJF.

                Article
                PONE-D-14-47808
                10.1371/journal.pone.0120749
                4398053
                25875198
                fab4cc3e-b62c-4b0e-8eb9-fb49045ee78f
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 17 November 2014
                : 6 February 2015
                Page count
                Figures: 2, Tables: 4, Pages: 13
                Funding
                AV received the Summer Studentship Research Grant from the Canadian Liver Foundation. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. URL is listed below: http://www.liver.ca/liver-education-liver-research/research/grant-programs/Grant_Recipients.aspx.
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                Research Article
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                All relevant data are within the paper.

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