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      High Hepatitis B Surface Antigen Levels Predict Insignificant Fibrosis in Hepatitis B e Antigen Positive Chronic Hepatitis B

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          Abstract

          Introduction

          There is no data on the relationship between hepatitis B surface antigen (HBsAg) levels and liver fibrosis in hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B (CHB).

          Methods

          Serum HBsAg and HBV DNA levels in HBeAg-positive CHB patients with liver biopsies were analyzed. The upper limit of normal (ULN) of alanine aminotransferase (ALT) was 30 and 19 U/L for men and women respectively. Histologic assessment was based on Ishak fibrosis staging for fibrosis and Knodell histologic activity index (HAI) for necroinflammation.

          Results

          140 patients (65% male, median age 32.7 years) were recruited. 56 (40%) had ALT ≤2×ULN. 72 (51.4%) and 42 (30%) had fibrosis score ≤1 and necroinflammation grading ≤4 respectively. Patients with fibrosis score ≤1, when compared to patients with fibrosis score >1, had significantly higher median HBsAg levels (50,320 and 7,820 IU/mL respectively, p<0.001). Among patients with ALT ≤2×ULN, serum HBsAg levels achieved an area under receiver operating characteristic curve of 0.869 in predicting fibrosis score ≤1. HBsAg levels did not accurately predict necroinflammation score. HBsAg ≥25,000 IU/mL was independently associated with fibrosis score ≤1 (p = 0.025, odds ratio 9.042).Using this cut-off HBsAg level in patients with ALT ≤2×ULN, positive and negative predictive values for predicting fibrosis score ≤1 were 92.7% and 60.0% respectively. HBV DNA levels had no association with liver histology.

          Conclusion

          Among HBeAg-positive patients with ALT ≤2×ULN, high serum HBsAg levels can accurately predict fibrosis score ≤1, and could potentially influence decisions concerning treatment commencement and reduce the need for liver biopsy.

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          Most cited references19

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          Histological grading and staging of chronic hepatitis.

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            Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update

            Large amounts of new data on the natural history and treatment of chronic hepatitis B virus (HBV) infection have become available since 2005. These include long-term follow-up studies in large community-based cohorts or asymptomatic subjects with chronic HBV infection, further studies on the role of HBV genotype/naturally occurring HBV mutations, treatment of drug resistance and new therapies. In addition, Pegylated interferon α2a, entecavir and telbivudine have been approved globally. To update HBV management guidelines, relevant new data were reviewed and assessed by experts from the region, and the significance of the reported findings were discussed and debated. The earlier “Asian-Pacific consensus statement on the management of chronic hepatitis B” was revised accordingly. The key terms used in the statement were also defined. The new guidelines include general management, special indications for liver biopsy in patients with persistently normal alanine aminotransferase, time to start or stop drug therapy, choice of drug to initiate therapy, when and how to monitor the patients during and after stopping drug therapy. Recommendations on the therapy of patients in special circumstances, including women in childbearing age, patients with antiviral drug resistance, concurrent viral infection, hepatic decompensation, patients receiving immune-suppressive medications or chemotherapy and patients in the setting of liver transplantation, are also included.
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              Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis.

              A Histology Activity Index has been developed which generates a numerical score for liver biopsy specimens obtained from patients with asymptomatic chronic active hepatitis. Biopsies are graded in four categories: periportal necrosis, intralobular necrosis, portal inflammation, and fibrosis. Under code, three pathologists and three hepatologists evaluated 14 liver biopsy specimens obtained from five patients with asymptomatic chronic active hepatitis. Good correlation was seen between severity of liver biopsy lesions as judged by conventional histological descriptions and Histology Activity Index scores. Significant differences in Histology Activity Index score occurred in only 2 or 28 duplicate scorings of biopsy specimens by two observers. This system provides definitive endpoints for statistical analysis of serial changes in liver histology and offers an alternative to the use of conventional pathological descriptions in following the natural history and treatment responses of asymptomatic chronic active hepatitis.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                20 August 2012
                : 7
                : 8
                : e43087
                Affiliations
                [1 ]Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong
                [2 ]Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong
                [3 ]State Key Laboratory for Liver Research, University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong
                Hannover Medical School, Germany
                Author notes

                Competing Interests: M.F. Yuen and J. Fung are academic editors of PLoS One. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials. No competing interests exist for the remaining authors.

                Conceived and designed the experiments: WKS DKHW MFY. Performed the experiments: JF PPCI JCHY IFNH. Analyzed the data: WKS. Contributed reagents/materials/analysis tools: JF PPCI JCHY IFNH. Wrote the paper: WKS. Critical revision of manuscript: CLL MFY. Study supervision: MFY.

                Article
                PONE-D-12-14282
                10.1371/journal.pone.0043087
                3423440
                22916211
                59ec421c-8133-4584-b3d5-28aecab0583f
                Copyright @ 2012

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 17 May 2012
                : 16 July 2012
                Page count
                Pages: 8
                Funding
                The authors have no support or funding to report.
                Categories
                Research Article
                Biology
                Immunology
                Immunity
                Inflammation
                Medicine
                Diagnostic Medicine
                Clinical Laboratory Sciences
                Gastroenterology and Hepatology
                Liver Diseases
                Infectious Hepatitis
                Hepatitis B
                Infectious Diseases
                Viral Diseases
                Hepatitis

                Uncategorized
                Uncategorized

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