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      Clinical characteristics and association analysis of persistent low-level HBsAg expression in a physical examination population with HBV infection

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          Abstract

          Certain patients with hepatitis B virus (HBV) infection present with persistently low levels of serum hepatitis B surface antigen (HBsAg) and have been indicated to have low rates of HBV nucleic acid replication. To explore the serological and molecular epidemiological characteristics of HBV population with low-level HBsAg in the present study, associated serum markers and virologic genotype detection were performed accordingly. Determination of HBV markers was performed using a chemiluminescence immunoassay from which 2,544 out of 45,256 adults who underwent routine health examination were tested positive for HBsAg. HBV DNA was detected by real-time fluorescent quantitative PCR. The patients were divided into low-level and high-level groups, according to their HBsAg levels (cut-off value, 10 IU/ml). The prevalence and levels of HBsAg positivity and HBV DNA in patients with HBV infection were analyzed by age, sex, serological pattern and clinical type. The fibrosis status of patients with low-level HBsAg was assessed by determining the aspartate aminotransferase-to-platelet ratio (APRI), and sequencing was employed to determine serotypes and genotypes. HBV-infected patients with low-level HBsAg (<10 IU/ml) accounted for 15.41% of the 2,544 HBsAg-positive patients, and the prevalence of HBsAg positivity exhibited a tendency to increase with age. The male-to-female ratio was ~1.9:1, and the average age was 54.98±16.28 years among HBV-infected patients with low-level HBsAg. The major serological pattern and clinical types were HBsAg/antibody against hepatitis Be antigen (anti-HBe)/antibody against hepatitis B core antigen (anti-HBc)-positive (94.90%) and chronic asymptomatic (ASC) (97.95%), respectively. HBV DNA exhibited a low-level of replication and the prevalence of HBV DNA positivity assessed by the routine method and by the enrichment method was 27.74% (97/392) and 45.92% (180/392), respectively. No significant differences among the age groups were identified in the different HBsAg level groups (P>0.05). The prevalence of HBV DNA positivity was associated with HBsAg only in patients with serological pattern HBV-M2 (HBsAg/anti-HBe/anti-HBc-positive) in the low-level HBsAg group (odds ratio: 1.30; 95% CI: 1.15–1.47; P<0.05). The APRI had no association with age, HBsAg, HBV DNA level or liver function index in ASC patients in the low-level HBsAg group (P>0.05). The prevalence of the serotype adw and genotype B was 85.53 and 89.47%, respectively. Further improvement in the systematic study of populations with low-level HBsAg has important clinical and epidemiological significance for improving the detection of HBV serological markers, elucidating the mechanisms leading to low-level HBsAg, overcoming immune tolerance to eliminate HBV infection and preventing HBV transmission.

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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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            Virologic and histologic features of chronic hepatitis B virus-infected asymptomatic patients with persistently normal ALT.

            There is a paucity of data on hepatitis B virus (HBV) DNA levels and histologic lesions in patients with chronic HBV (CHBV) infection and persistently normal alanine aminotransferase (ALT) levels (PNALT). We studied the ALT, HBV DNA levels, and spectrum of histologic lesions in such patients. One thousand three hundred eighty-seven incidentally detected asymptomatic hepatitis B surface antigen (HBsAg)-positive patients with >/=1-year follow-up and either PNALT (n = 189; hepatitis B e antigen [HBeAg(+)], 73; HBeAg(-), 116) or persistently or intermittently elevated ALT (PIEALT; n = 1198; HBeAg(+), 530; HBeAg(-), 668) were included. In the PIEALT and PNALT patients, baseline DNA >/=5-log copies/mL was seen in 73.8% and 60.3% in HBeAg(+) (P = .018) and 76% and 35.3% in HBeAg(-) (P /=2 in 65.5% and 40.2% in HBeAg(+) (P /=3 and/or fibrosis stage >/=2). A fair proportion of patients with CHBV infection with PNALT have HBV DNA >/=5-log copies/mL and significant histologic fibrosis. Use of ALT and HBV DNA levels without resorting to liver biopsy to define "inactive carrier state" in HBeAg(-) PNALT patients may miss histologically significant disease in a proportion of patients.
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              Evaluation of the impact of hepatitis B vaccination among children born during 1992-2005 in China.

              Endemic hepatitis B virus (HBV) infection is a serious health problem in China. Hepatitis B vaccination of infants was introduced in 1992 and was progressively expanded during the subsequent 15 years. We conducted a national serosurvey, with participants selected by multiple-stage random sampling. Demographic characteristics and hepatitis B vaccination history were collected by a questionnaire and a review of vaccination records, and serum specimens were tested for hepatitis B surface antigen, antibody to hepatitis B core antigen, and hepatitis B surface antibody by enzyme-linked immunosorbent assay. Hepatitis B vaccine coverage (3 doses) increased from 30.0% for children born in 1992 to 93.4% for children born in 2005. Receipt of a timely birth dose increased from 22.2% to 82.6% for children born during this interval. Multivariate analysis showed that older age, western and rural residence, birth at home, and certain ethnicities were risk factors for under vaccination with both full vaccine series and timely birth dose. The prevalence of hepatitis B surface antigen was reduced to 2.1% among all children and 1.0% among children born after 1999. The efficacy of hepatitis B vaccination with a timely birth dose was 88.3%. Hepatitis B vaccine has been successfully integrated into routine infant immunization in China, now reaching most infants within 24 h after birth, and the prevalence of hepatitis B surface antigen has been greatly reduced among children born after 1992.
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                Author and article information

                Journal
                Exp Ther Med
                Exp Ther Med
                ETM
                Experimental and Therapeutic Medicine
                D.A. Spandidos
                1792-0981
                1792-1015
                January 2020
                19 November 2019
                19 November 2019
                : 19
                : 1
                : 19-32
                Affiliations
                [1 ]Department of Clinical Laboratory, The 903rd Hospital of The PLA, Hangzhou, Zhejiang 310013, P.R. China
                [2 ]Department of Laboratory Medicine, Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
                [3 ]Department of Respiration, The 903rd Hospital of The PLA, Hangzhou, Zhejiang 310013, P.R. China
                [4 ]Department of Biotechnology, University of Tokyo, Tokyo 1138656, Japan
                [5 ]Department of Medical Laboratory, Faculty of Graduate Studies, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China
                [6 ]Department of Medical Laboratory, Faculty of Graduate Studies, Bengbu Medical College, Bengbu, Anhui 233000, P.R. China
                Author notes
                Correspondence to: Professor Jun Cheng, Department of Clinical Laboratory, The 903rd Hospital of The PLA, 14 Lingyin Road, Westlake, Hangzhou, Zhejiang 310013, P.R. China, E-mail: cj1171967@ 123456163.com
                [*]

                Contributed equally

                Article
                ETM-0-0-8217
                10.3892/etm.2019.8217
                6909745
                31853269
                0b249a90-a849-4979-b903-cf8d336fb2d9
                Copyright: © Dai et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 03 January 2019
                : 05 August 2019
                Categories
                Articles

                Medicine
                physical examination population,hepatitis b virus markers,hepatitis b virus infection,hepatitis b surface antigen,hepatitis b virus dna

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