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      Occult Hepatitis B Virus Infection in Maintenance Hemodialysis Patients: Prevalence and Mutations in “a” Determinant

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          Abstract

          Background: Occult hepatitis B virus infection (OBI) is defined as undetectable serum hepatitis B surface antigen (HBsAg) with detectable HBV-DNA in the serum or liver. Patients with maintenance hemodialysis (MHD) are at a high risk of OBI. The prevalence of OBI in MHD patients in China is not well evaluated. In this study, we aim to assess the prevalence of OBI in MHD patients in Sichuan Province, Southwest of China and investigate the mutations in the “a” determinant of HBsAg.

          Methods: A total of 330 patients undergoing MHD at Sichuan Provincial People's Hospital were enrolled. Serum samples were collected for ELISA assay to test the serological markers of HBV infection, real-time PCR assay to identify the presence of HBV-DNA, and nested PCR plus sequencing analysis to investigate the gene mutations.

          Results: In a total of 330 MHD patients, we found that the prevalence of OBI was 4.2% (7/165) in the test group, 2.1% (7/330) in the overall dialysis cohort. After a follow-up study of 7 MHD patients with OBI for 2 years, 2 (isolated HBcAb+) of them were still detectable for HBV-DNA. By sequencing analysis, we revealed mutations at the “a” determinant of HBsAg, including Q129R, T131N, M133S, F134L and D144E. The Q129R and M133S mutations were first reported.

          Conclusions: Our study clarifies the prevalence of OBI in MHD patients in Sichuan Province(4.2% in the test group, 2.1% in the overall dialysis cohort), and demonstrate the mutations of Q129R and M133S in the “a” determinant of HBsAg for the first time.

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          Most cited references16

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          Epidemiology of Hepatitis B Virus Infection and Impact of Vaccination on Disease.

          Integration of hepatitis B vaccination into national immunization programs has resulted in substantial reductions of hepatitis B virus (HBV) transmission in previously high endemic countries. The key strategy for control of the HBV epidemic is birth dose and infant vaccination. Additional measures include use of hepatitis B immunoglobulin (HBIG) and diagnosis of mothers at high risk of transmitting HBV and use of antiviral agents during pregnancy to decrease maternal DNA concentrations to undetectable concentrations. Despite the substantial decrease in HBV cases since vaccination introduction, implementation of birth dose vaccination in low-income and middle-income countries and vaccination of high-risk adults remain challenging.
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            Molecular mechanisms underlying occult hepatitis B virus infection.

            Chronic hepatitis B virus (HBV) infection is a complex clinical entity frequently associated with cirrhosis and hepatocellular carcinoma (HCC). The persistence of HBV genomes in the absence of detectable surface antigenemia is termed occult HBV infection. Mutations in the surface gene rendering HBsAg undetectable by commercial assays and inhibition of HBV by suppression of viral replication and viral proteins represent two fundamentally different mechanisms that lead to occult HBV infections. The molecular mechanisms underlying occult HBV infections, including recently identified mechanisms associated with the suppression of HBV replication and inhibition of HBV proteins, are reviewed in detail. The availability of highly sensitive molecular methods has led to increased detection of occult HBV infections in various clinical settings. The clinical relevance of occult HBV infection and the utility of appropriate diagnostic methods to detect occult HBV infection are discussed. The need for specific guidelines on the diagnosis and management of occult HBV infection is being increasingly recognized; the aspects of mechanistic studies that warrant further investigation are discussed in the final section.
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              Occult hepatitis B virus infection: a covert operation.

              Detection of occult hepatitis B requires assays of the highest sensitivity and specificity with a lower limit of detection of less than 10 IU/mL for hepatitis B virus (HBV) DNA and <0.1 ng/mL for hepatitis B surface antigen (HBsAg). This covert condition is relatively common in patients with chronic hepatitis C virus (HCV) that seems to exert some influence on the replicative capacity and latency of HBV. Detection of virus-specific nucleic acid does not always translate into infectivity, and the occurrence of primer-generated HBV DNA that is of partial genomic length in immunocompetent individuals who have significant levels of hepatitis B surface antibody (anti-HBs) may not be biologically relevant. Acute flares of alanine aminotransferase (ALT) that occur during the early phase of therapy for HCV or ALT levels that remain elevated at the end of therapy in biochemical nonresponders should prompt an assessment for occult hepatitis B. Similarly, the plasma from patients with chronic hepatitis C that is hepatitis B core antibody (anti-HBc) positive (+/-anti-HBs at levels of <100 mIU/mL) should be examined for HBV DNA with the most sensitive assay available. If a liver biopsy is available, immunostaining for hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) should be contemplated and a portion of the sample tested for HBV DNA. This is another reason for optimal collection of a specimen (e.g. two passes with a 16-guage needle under ultrasound guidance). Transmission of HBV to immunosuppressed orthotopic liver transplant recipients by donors with occult hepatitis B (OHB) will continue to occupy the interests of the transplant hepatologist. As patients with OHB may have detectable HBV DNA in serum, peripheral blood mononuclear cells (PBMC) and/or liver that can be reactivated following immunosuppression or intensive cytotoxic chemotherapy, the patient needs to be either monitored or treated depending on the pretreatment serological results such as an isolated anti-HBc reaction or a detectable HBV DNA.
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                Author and article information

                Journal
                Int J Med Sci
                Int J Med Sci
                ijms
                International Journal of Medical Sciences
                Ivyspring International Publisher (Sydney )
                1449-1907
                2020
                25 August 2020
                : 17
                : 15
                : 2299-2305
                Affiliations
                [1 ]Department of Nephrology, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, Sichuan, China.
                [2 ]Department of Clinical Laboratory, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, Sichuan, China.
                [3 ]School of Medicine, Nanchang University, Nanchang 330047, China.
                Author notes
                ✉ Corresponding author: Dr. Yang Zou (Email: zouyang@ 123456med.uestc.edu.cn )

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                ijmsv17p2299
                10.7150/ijms.49540
                7484637
                32922195
                be1a5743-e6b9-4703-a677-a1bd5cfb7c10
                © The author(s)

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                : 16 June 2020
                : 12 August 2020
                Categories
                Research Paper

                Medicine
                occult hepatitis b virus infection(obi),maintenance hemodialysis,prevalence,amino acid mutation,genotype

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