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      Anti-hepatitis B core antigen testing with detection and characterization of occult hepatitis B virus by an in-house nucleic acid testing among blood donors in Behrampur, Ganjam, Orissa in southeastern India: implications for transfusion

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          Abstract

          Background

          Occult hepatitis B virus (HBV) infection might transmit viremic units into the public blood supply if only hepatitis B surface antigen (HBsAg) testing is used for donor screening. Our aim was to evaluate the prevalence of occult HBV infection among the HBsAg negative/antiHBc positive donations from a highly HIV prevalent region of India.

          Methods

          A total of 729 HBsAg negative donor units were included in this study. Surface gene and precore region were amplified by in house nucleic acid test (NAT) for detection of occult HBV infection and surface gene was analyzed after direct sequencing.

          Results

          A total of 220 (30.1%) HBsAg negative donors were antiHBc positive, of them 66 (30%) were HBV DNA positive by NAT. HBV DNA positivity among 164 antiHBc only group, was 27.1% and among 40 antiHBs positive group was 30.0%. HBV/D (93.3%) was predominant and prevalence of both HBV/C and HBV/A was 3.3%. Single or multiple amino acids substitutions were found in 95% samples.

          Conclusion

          Thus, a considerable number of HBV infected donors remain undiagnosed, if only HBsAg is used for screening. Addition of antiHBc testing for donor screening, although will lead to rejection of a large number of donor units, will definitely eliminate HBV infected donations and help in reducing HBV transmission with its potential consequences, especially among the immunocompromised population. The HBV genetic diversity found in this donor population are in accordance with other parts of India.

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          Most cited references26

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          Genetic diversity of hepatitis B virus strains derived worldwide: genotypes, subgenotypes, and HBsAg subtypes.

          Sequences of 234 complete genomes and 631 hepatitis B surface antigen genes were used to assess the worldwide diversity of hepatitis B virus (HBV). Apart from the described two subgenotypes each for A and F, also B, C, and D divided into four subgenotypes each in the analysis of complete genomes supported by significant bootstrap values. The subgenotypes of B and C differed in their geographical distribution, with B1 dominating in Japan, B2 in China and Vietnam, B3 confined to Indonesia, and B4 confined to Vietnam, all strains specifying subtype ayw1. Subgenotype C1 was common in Japan, Korea, and China; C2 in China, South-East Asia, and Bangladesh, and C3 in the Oceania comprising strains specifying adrq-, and C4 specifying ayw3 is encountered in Aborigines from Australia. This pattern of defined geographical distribution was less evident for D1-D4, where the subgenotypes were widely spread in Europe, Africa, and Asia, possibly due to their divergence having occurred a longer time ago than for genotypes B and C, with D4 being the first split and still the dominating subgenotype of D in the Oceania. The genetic diversity of HBV and the geographical distribution of its subgenotypes provide a tool to reconstruct the evolutionary history of HBV and may help to complement genetic data in the understanding of the evolution and past migrations of man. 2004 S. Karger AG, Basel.
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            Occult hepatitis B virus infection and its clinical implications.

            Qin Hu (2002)
            Occult hepatitis B virus (HBV) infection is characterized by presence of HBV infection with undetectable hepatitis B surface antigen (HBsAg). Serum HBV level is usually less than 104 copies/mL in these patients. Diagnosis of occult HBV infection requires sensitive HBV-DNA PCR assay. Several possibilities have been hypothesized as the mechanisms of occult HBV infection. These include: (i) mutations of HBV-DNA sequence; (ii) integration of HBV-DNA into host's chromosomes; (iii) infection of peripheral blood mononuclear cells by HBV; (iv) formation of HBV-containing immune complex; (v) altered host immune response; and (vi) interference of HBV by other viruses. The precise prevalence of occult HBV infection remains to be defined. The clinical implications of occult HBV infection involve different clinical aspects. First of all, occult HBV infection harbours potential risk of HBV transmission through blood transfusion, haemodialysis, and organ transplantation. Second, it may serve as the cause of cryptogenic liver disease, contribute to acute exacerbation of chronic hepatitis B, or even fulminant hepatitis. Third, it is associated with development of hepatocellular carcinoma. Fourth, it may affect disease progression and treatment response of chronic hepatitis C. Most of the previous studies utilized retrospective observation without control groups, and lacked direct association of occult HBV infection with specific pathological changes and disease progression. Highly sensitive, quantitative, and functional molecular analyses of HBV, combined with a well-designed prospective clinical assessment will provide the best approach for the future study of occult HBV infection.
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              Hepatitis B virus maintains its pro-oncogenic properties in the case of occult HBV infection.

              Occult hepatitis B virus (HBV) infection is characterized by persistence of HBV DNA into the tissue of hepatitis B surface antigen-negative individuals. The clinical relevance of this peculiar infection is still under debate. In particular, the impact of occult HBV infection in cases of hepatocellular carcinoma (HCC) is uncertain. We investigated the prevalence and molecular status of occult HBV in patients with HCC. We tested tumor tissues from 107 patients with HCC and the corresponding nontumor liver tissue from 72 of these patients for HBV DNA. We also examined liver specimens from 192 patients with chronic hepatitis. All cases were hepatitis B surface antigen negative. Covalently closed circular HBV genomes, HBV transcripts, and viral integrated forms were investigated in cases of HCC found positive for occult HBV. Viral DNA was detected in 68 of 107 cases of HCC (63.5%) and in 63 of 192 cases of chronic hepatitis (32.8%) (P < 0.0001; odds ratio, 3.6; 95% confidence interval, 2.2-5.9). The significant association of occult HBV with HCC was irrespective of age, sex, and contemporary hepatitis C virus infection. Both integrated viral DNA and covalently closed circular HBV genomes were detected in patients with occult HBV. Moreover, the presence of free HBV genomes was associated with persistence of viral transcription and replication. Our findings provide clear evidence that occult HBV is a risk factor for development of HCC and show that the potential mechanisms whereby overt HBV might induce tumor formation are mostly maintained in cases of occult infection.
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                Author and article information

                Journal
                Virol J
                Virology Journal
                BioMed Central
                1743-422X
                2010
                27 August 2010
                : 7
                : 204
                Affiliations
                [1 ]Defence Research Laboratory, Tezpur, Assam-784001, India
                [2 ]Division of Infectious Diseases and Immunology, Saint Louis University, St Louis, 63104 MO, USA
                [3 ]Department of Pathology & Laboratory Medicine, Tulane University School of Medicine, New Orleans, 70112 LA, USA
                [4 ]ICMR Virus Unit, Kolkata, ID & BG Hospital Campus, Kolkata, India
                [5 ]National Institute of Cholera and Enteric Diseases, Kolkata, India
                [6 ]Red Cross Blood Bank, M.K.C.G. Medical College, Behrampur, Orissa, India
                [7 ]Department of Chemistry, Jadavpur University, Kolkata, India
                Article
                1743-422X-7-204
                10.1186/1743-422X-7-204
                2942823
                20799931
                ba80ab14-a178-46b8-a1c5-645a546946d4
                Copyright ©2010 Panigrahi et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 May 2010
                : 27 August 2010
                Categories
                Research

                Microbiology & Virology
                Microbiology & Virology

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