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      Serum hepatitis B surface antigen titer and transient elastography in screening for insignificant fibrosis in HBeAg-positive chronic hepatitis B patients

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          To explore the predictive value of serum hepatitis B surface antigen (HBsAg) titer and transient elastography in screening for insignificant fibrosis in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients.


          We conducted a cross-sectional study of eligible patients treated from March 2012 to May 2013 at the West China Hospital of Sichuan University. Eligible patients underwent liver transient elastography and liver biopsy. We assessed the serum HBsAg level, serum hepatitis B virus (HBV) deoxyribonucleic acid (DNA) level, HBV genotypes, liver stiffness measurement (LSM) values by transient elastography, and histological fibrosis staging by METAVIR classification.


          A total of 129 consecutive patients were recruited. The LSM value ( P<0.001, odds ratio 14.67, 95% CI 0.158–0.551) and log 10HBsAg ( P=0.045, odds ratio 4.03, 95% CI 0.136–0.976) correlated with a liver fibrosis score <F2, independently. Inverse correlations were found between log 10HBsAg and the LSM value ( r=−576, P<0.001) and fibrosis staging ( r=−374, P<0.001). Patients with a fibrosis score <F2 had a significantly higher log 10HBsAg than patients with a fibrosis score ≥F2 among those with an LSM value under 9.4 kPa (4.6±0.7 vs 4.3±0.5, P=0.006). The HBsAg titer achieved an area under the receiver operating characteristic curve of 0.758 ( P<0.001, 95% CI 0.631–0.884) in predicting a fibrosis score <F2, with a cut-off value of 10,400 IU/mL, a positive predictive value of 73%, and a negative predictive value of 79%.


          In HBeAg-positive patients with an alanine aminotransferase level <2× the upper limit of normal, high serum HBsAg levels can predict a fibrosis score <F2, and a lower HBsAg titer could be supportive of early fibrosis in patients with an LSM value under 9.4 kPa.

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          Most cited references 19

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          Global control of hepatitis B virus infection.

          Worldwide about 350 million people are chronic carriers of the hepatitis B virus (HBV). The infection can cause acute and chronic liver disease including cirrhosis and hepatocellular carcinoma (HCC). Hepatocellular injuries of HBV infection are predominantly immune-mediated, and the natural history of chronic infection can be divided into three phases based on virus-host interactions-namely, immune tolerance, immune clearance, and viral integration phases. Four serotypes (adw, ayw, adr, and ayr) and seven genotypes (A to G) of HBV have been identified, and they show some distinct geographic distributions. The HBV genotypes may have clinical relevance and are currently under investigation. On the basis of disease burden and the availability of safe and effective vaccines, the WHO recommended that by the end of the 20th century hepatitis B vaccine be incorporated into routine infant and childhood immunisation programmes for all countries. The efficacy of universal immunisation has been shown in different countries, with striking reductions of the prevalence of HBV carriage in children. Most important, hepatitis B vaccination can protect children against HCC and fulminant hepatitis, as has been shown in Taiwan. Nevertheless, the implementation of worldwide vaccination against HBV requires greater effort to overcome the social and economic hurdles. Safe and effective antiviral treatments are available but are still far from ideal, a situation that, hopefully, will be improved soon. With hepatitis B immunisation, the global control of HBV infection is possible by the end of the first half of 21st century.
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            Diagnostic accuracy of FibroScan and comparison to liver fibrosis biomarkers in chronic viral hepatitis: a multicenter prospective study (the FIBROSTIC study).

            The diagnostic accuracy of non-invasive liver fibrosis tests that may replace liver biopsy in patients with chronic hepatitis remains controversial. We assessed and compared the accuracy of FibroScan® and that of the main biomarkers used for predicting cirrhosis and significant fibrosis (METAVIR ≥ F2) in patients with chronic viral hepatitis. A multicenter prospective cross-sectional diagnostic accuracy study was conducted in the Hepatology departments of 23 French university hospitals. Index tests and reference standard (METAVIR fibrosis score on liver biopsy) were measured on the same day and interpreted blindly. Consecutive patients with chronic viral hepatitis (hepatitis B or C virus, including possible Human Immunodeficiency Virus co-infection) requiring liver biopsy were recruited in the study. The analysis was first conducted on the total population (1839 patients), and after excluding 532 protocol deviations, on 1307 patients (non-compliant FibroScan® examinations). The overall accuracy of FibroScan® was high (AUROC 0.89 and 0.90, respectively) and significantly higher than that of biomarkers in predicting cirrhosis (AUROC 0.77-0.86). All non-invasive methods had a moderate accuracy in predicting significant fibrosis (AUROC 0.72-0.78). Based on multilevel likelihood ratios, non-invasive tests provided a relevant gain in the likelihood of diagnosis in 0-60% of patients (cirrhosis) and 9-30% of patients (significant fibrosis). The diagnostic accuracy of non-invasive tests was high for cirrhosis, but poor for significant fibrosis. A clinically relevant gain in the likelihood of diagnosis was achieved in a low proportion of patients. Although the diagnosis of cirrhosis may rely on non-invasive tests, liver biopsy is warranted to diagnose intermediate stages of fibrosis. Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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              Hepatitis B surface antigen (HBsAg) levels in the natural history of hepatitis B virus (HBV)-infection: a European perspective.

              The quantifiable level of HBsAg has been suggested as a predictor of treatment response in chronic hepatitis B. However, there is limited information on HBsAg levels considering the dynamic natural course of HBV-infection. This study aimed to determine HBsAg levels in the different phases of HBV-infection in European HBsAg-positive patients. 226 HBV-monoinfected patients, not undergoing antiviral therapy, were analyzed in a cross-sectional study. Patients were categorized according to the phase of HBV-infection: HBeAg(+) immune tolerance phase (IT, n=30), immune clearance phase (IC, n=48), HBeAg(-) low-replicative phase (LR, n=68), HBeAg(-) hepatitis (ENH, n=68), and acute hepatitis B (n=12). HBsAg was quantified and correlated with HBV-DNA, HBV-genotypes and clinical parameters. In addition, 30 LR-patients were followed longitudinally. HBsAg levels were higher in IT-patients and IC-patients compared to LR-patients and ENH-patients (4.96/4.37/3.09/3.87-log(10)IU/ml, p 2000IU/ml) showed >3-fold higher baseline HBsAg levels with a NPV of 95% for an HBsAg cut-off of 3500IU/ml. HBsAg levels show significant differences during the natural course of HBV-infection and between HBV-genotypes. These findings may have important implications for understanding the natural history of HBV-infection and for using quantitative HBsAg as a diagnostic tool, i.e. as a marker for predicting HBV-reactivation.

                Author and article information

                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                13 February 2015
                : 11
                : 229-235
                Center of Infectious Disease, West China Hospital, West China School of Medicine, and State Key Laboratory of Biotherapy, Sichuan University, Chengdu, People’s Republic of China
                Author notes
                Correspondence: Hong Tang, Center of Infectious disease and State Key Laboratory of Biotherapy, West China Hospital, West China School of Medicine, Sichuan University, 37# Guoxue Lane, Chengdu 610041, People’s Republic of China, Tel +86 28 8542 3052, Fax +86 28 8542 3052, Email htang6198@ 123456hotmail.com
                © 2015 Liang et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Original Research


                hepatitis b e antigen, hbsag, hbv


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