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      THE IMPACT OF POSITIVE ANTI-HBC MARKER ON PERMANENT DEFERRAL OF VOLUNTARY BLOOD DONORS IN EASTERN CROATIA AND ESTIMATION OF OCCULT HEPATITIS B VIRUS INFECTION RATE

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          SUMMARY

          Recently an increase has been reported in the number of HBV transmissions from anti-HBc positive blood donors that were repeatedly negative in HBsAg and nucleic acid testing using the most sensitive tests available. The aim of the study was to show the effect of anti-HBc antibody testing performed in 2006 on permanent deferral of voluntary blood donors (VBDs), and to estimate occult hepatitis B infection (OBI) rate in this population after the introduction of mandatory molecular testing in the 2013-2016 period. More than 30,000 blood donations collected during the 2005-2007 period and more than 14,000 VBDs having donated blood during the 2013-2016 period after the introduction of molecular testing from eastern Croatia were included in the study. Serologic testing was performed with HBsAg assay throughout the study period, and anti-HBc assay was only performed in 2006. As part of the confirmatory algorithm testing, all HBsAg positive and unclear results were tested with molecular tests. Anti-HBc prevalence among VBDs in 2006 was 1.5%, with a rate of 1:197, whereas HBsAg prevalence was stable from 2005 to 2007 (0.04%, 0.1% and 0.1%, respectively). The calculated OBI rate from 2013 to 2016 was 1:30,250. Ten of 161 (12.4%) VBDs had serologic anti-HBc-only pattern. Anti-HBc testing in 2006 resulted in statistically more deferrals of VBDs compared to 2005 and 2007, and to the rest of Republic of Croatia. The strategy of universal anti-HBc testing of VBDs in addition to the existing HBsAg and molecular screening could be an additional measure to prevent HBV transmission by blood and blood components.

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          Update of the statements on biology and clinical impact of occult hepatitis b virus infection

          In October 2018 a large number of international experts with complementary expertise came together in Taormina to participate in a workshop on occult hepatitis B virus infection (OBI). The objectives of the workshop were to review the existing knowledge on OBI, to identify issues that require further investigation, to highlight both existing controversies and newly emerging perspectives, and ultimately to update the statements previously agreed in 2008. This paper represents the output from the workshop.
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            Medical Virology of Hepatitis B: how it began and where we are now

            Infection with hepatitis B virus (HBV) may lead to acute or chronic hepatitis. HBV infections were previously much more frequent but there are still 240 million chronic HBV carriers today and ca. 620,000 die per year from the late sequelae liver cirrhosis or hepatocellular carcinoma. Hepatitis B was recognized as a disease in ancient times, but its etiologic agent was only recently identified. The first clue in unraveling this mystery was the discovery of an enigmatic serum protein named Australia antigen 50 years ago by Baruch Blumberg. Some years later this was recognized to be the HBV surface antigen (HBsAg). Detection of HBsAg allowed for the first time screening of inapparently infected blood donors for a dangerous pathogen. The need to diagnose clinically silent HBV infections was a strong driving force in the development of modern virus diagnostics. HBsAg was the first infection marker to be assayed with a highly sensitive radio immune assay. HBV itself was among the first viruses to be detected by assay of its DNA genome and IgM antibodies against the HBV core antigen were the first to be selectively detected by the anti-μ capture assay. The cloning and sequencing of the HBV genome in 1978 paved the way to understand the viral life cycle, and allowed development of efficient vaccines and drugs. Today’s hepatitis B vaccine was the first vaccine produced by gene technology. Among the problems that still remain today are the inability to achieve a complete cure of chronic HBV infections, the recognition of occult HBV infections, their potential reactivation and the incomplete protection against escape mutants and heterologous HBV genotypes by HBV vaccines.
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              Occult hepatitis B virus infection.

              Occult hepatitis B virus (HBV) infection (OBI) refers to the presence of HBV DNA in the absence of detectable hepatitis B surface antigen. Since OBI was first described in the late 1970s, there has been increasing interest in this topic. The prevalence of OBI varies according to the different endemicity of HBV infection, cohort characteristics, and sensitivity and specificity of the methods used for detection. Although the exact mechanism of OBI has not been proved, intra-hepatic persistence of viral covalently closed circular DNA under the host's strong immune suppression of HBV replication and gene expression seems to be a cause. OBI has important clinical significance in several conditions. First, OBI can be transmitted through transfusion, organ transplantation including orthotopic liver transplantation, or hemodialysis. Donor screening before blood transfusion, prophylaxis for high-risk organ transplantation recipients, and dialysis-specific infection-control programs should be considered to reduce the risk of transmission. Second, OBI may reactivate and cause acute hepatitis in immunocompromised patients or those receiving chemotherapy. Close HBV DNA monitoring and timely antiviral treatment can prevent HBV reactivation and consequent clinical deterioration. Third, OBI may contribute to the progression of hepatic fibrosis in patients with chronic liver disease including hepatitis C. Finally, OBI seems to be a risk factor for hepatocellular carcinoma by its direct proto-oncogenic effect and by indirectly causing persistent hepatic inflammation and fibrosis. However, this needs further investigation. We review published reports in the literature to gain an overview of the status of OBI and emphasize the clinical importance of OBI.
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                Author and article information

                Journal
                Acta Clin Croat
                Acta Clin Croat
                ACC
                Acta Clinica Croatica
                Sestre Milosrdnice University Hospital and Institute of Clinical Medical Research, Vinogradska cesta c. 29 Zagreb
                0353-9466
                1333-9451
                March 2020
                March 2020
                : 59
                : 1
                : 126-134
                Affiliations
                Nord-Trøndelag Hospital Trust, Namsos Hospital, Department of Internal Medicine, Namsos, Norway; Osijek University Hospital Centre, Department of Transfusion Medicine , Osijek, Croatia; Faculty of Medicine, Josip Juraj Strossmayer University of Osijek , Osijek, Croatia; Croatian Institute of Transfusion Medicine, Zagreb, Croatia; Merkur University Hospital, Department of Internal Medicine , Zagreb, Croatia; Osijek University Hospital Centre, Department of Internal Medicine, Division of Gastroenterology and Hepatology , Osijek, Croatia
                Author notes
                Correspondence to: Assoc. Prof. Domagoj Drenjančević, MD, PhD, Department of Transfusion Medicine, Osijek University Hospital Centre, Josipa Huttlera 4, HR-31000 Osijek, Croatia, E-mail: drenjancevic.domagoj@ 123456kbco.hr
                Article
                acc-59-126
                10.20471/acc.2020.59.01.15
                7382879
                32724283
                1a8b182f-6f9c-45f6-a440-40ce882a69cb
                Copyright @ 2020

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (CC BY-NC-ND) 4.0 License.

                History
                : 29 January 2020
                : 28 February 2020
                Categories
                Original Scientific Papers

                blood donors,hepatitis b,hepatitis b virus,hepatitis b surface antigen,croatia

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