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      Serum hepatitis B core antibody as a biomarker of hepatic inflammation in chronic hepatitis B patients with normal alanine aminotransferase

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          Abstract

          Our previous studies unexpectedly indicated that the level of serum hepatitis B core antibody (anti-HBc) was positively correlated with the serum alanine aminotransferase (ALT) level. The aim of this study was to determine whether anti-HBc could serve as a potential biomarker for the detection of liver inflammation in chronic hepatitis B (CHB) patients, especially in patients with normal ALT levels. Serum anti-HBc levels were quantified in 655 treatment-naïve CHB patients, including 45 patients who underwent two liver biopsies (baseline phase and the 78 th weeks of antiviral-treatment). Serum anti-HBc levels increased significantly along with the increasing histology activity index (HAI) score. After antiviral-treatment, patients with HAI score reduction had significant decline in serum anti-HBc level. Multivariate analysis showed that anti-HBc was independently associated with moderate-to-severe hepatic inflammation in patients with normal ALT level. Furthermore, serum anti-HBc showed a high diagnostic accuracy for predicting moderate-to-severe inflammation in both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative CHB patients with normal ALT levels (area under the curve, AUC = 0.87 and 0.75; respectively). Thus, anti-HBc may be a strong indicator for assessing the hepatic inflammatory degree and used for antiviral treatment decisions in CHB patients with normal ALT levels.

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          Most cited references 19

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          Hepatitis B virus infection.

          Since the introduction of the hepatitis B vaccine and other preventive measures, the worldwide prevalence of hepatitis B infection has fallen. However, chronic infection remains a challenging global health problem, with more than 350 million people chronically infected and at risk of hepatic decompensation, cirrhosis, and hepatocellular carcinoma. An improved understanding of hepatitis B virology, immunology, and the natural course of chronic infection, has identified hepatitis B virus replication as the key driver of immune-mediated liver injury and disease progression. The approval of potent oral antiviral agents has revolutionised hepatitis B treatment since 1998. Conventional and pegylated interferon alfa and nucleoside and nucleotide analogues are widely authorised treatments, and monotherapy with these drugs greatly suppresses virus replication, reduces hepatitis activity, and halts disease progression. However, hepatitis B virus is rarely eliminated, and drug resistance is a major drawback during long term therapy. The development of new drugs and strategies is needed to improve treatment outcomes.
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            Inflammation and liver cancer: new molecular links .

            A connection between inflammation and cancer has been long suspected. Epidemiological studies have established that many tumors occur in association with chronic infectious diseases, and it is also known that persistent inflammation in the absence of infections increases the risk and accelerates the development of cancer. One clear example of inflammation-related cancer is hepatocellular carcinoma (HCC). HCC is a type tumor that slowly unfolds on a background of chronic inflammation mainly triggered by exposure to infectious agents (hepatotropic viruses) or to toxic compounds (ethanol). The molecular links that connect inflammation and cancer are not completely known, but evidences gathered over the past few years are beginning to define the precise mechanisms. In this article we review the most compelling evidences on the role of transcription factors such as NF-kappaB and STAT3, cytokines like IL-6 and IL-1alpha, ligands of the EGF receptor and other inflammatory mediators in cancer development, with special emphasis in HCC. The molecular dissection of the pathways connecting the inflammatory reaction and neoplasia will pave the way for better therapies to treat cancers.
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              Management of hepatitis B: our practice and how it relates to the guidelines.

              Seven drugs have been approved for the treatment of chronic hepatitis B. Antiviral treatment has been shown to be effective in suppressing hepatitis B virus replication, decreasing inflammation and fibrosis in the liver, and preventing progression of liver disease. However, current medications do not eradicate hepatitis B virus; therefore, a key question is which patients need to start treatment and which patients can be monitored. Professional societies have developed guidelines to assist physicians in recognition, diagnosis, and optimal management of patients with chronic hepatitis B. These guidelines suggest preferred approaches, and physicians are expected to exercise clinical judgment to determine the most appropriate management based on the circumstances of the individual patient. This article reviews recommendations in hepatitis B guidelines and the basis for those recommendations, and we discuss what we do in our practice to illustrate factors that may influence decisions regarding hepatitis B management.
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                Author and article information

                Contributors
                nsxia@xmu.edu.cn
                john131212@126.com
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                5 June 2017
                5 June 2017
                2017
                : 7
                Affiliations
                [1 ]ISNI 0000 0004 1764 1621, GRID grid.411472.5, Department of Infectious Disease, , Center for Liver Disease, Peking University First Hospital, ; Beijing, China
                [2 ]ISNI 0000 0001 2264 7233, GRID grid.12955.3a, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, , National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, ; Xiamen, China
                [3 ]ISNI 0000 0004 1771 3349, GRID grid.415954.8, Department of Infectious Disease, , China-Japan Friendship Hospital, ; Beijing, China
                [4 ]ISNI 0000 0004 1762 1794, GRID grid.412558.f, Department of Infectious Disease, , The Third Affiliated Hospital Sun Yat-Sen University, ; Guangzhou, Guangdong China
                [5 ]ISNI 0000 0004 1760 6682, GRID grid.410570.7, Department of Infectious Diseases, , South West Hospital affiliated to Third Military Medical University, ; Chongqing, China
                [6 ]GRID grid.412461.4, Department of Infectious Diseases, , Second Affiliated Hospital of Chongqing Medical University, ; Chongqing, China
                [7 ]ISNI 0000 0004 0368 8293, GRID grid.16821.3c, Department of Infectious Diseases, , Rui Jin Hospital Shanghai Jiao Tong University School of Medicine, ; Shanghai, China
                [8 ]Department of Infectious Diseases, The People’s Hospital of Guang Xi Zhuang Autonomous Region, Nanning, Guangxi China
                [9 ]Department of Infectious Diseases, The People’s Hospital of He Nan Province, Zhengzhou, Henan China
                [10 ]ISNI 0000 0004 0369 153X, GRID grid.24696.3f, Department of Infectious Diseases, , Di Tan Hospital affiliated to Capital Medical University, ; Beijing, China
                [11 ]ISNI 0000 0004 1808 322X, GRID grid.412990.7, Department of Infectious Diseases, , Xinxiang Medical University Third Hospital, ; Xinxiang, Henan China
                [12 ]Department of Infectious Diseases, Yan tai City Hospital for Infectious Disease, Yan tai, Shandong China
                [13 ]Department of Infectious Diseases, Shenyang Sixth People’s Hospital, Shenyang, Liaoning China
                [14 ]ISNI 0000 0004 1759 700X, GRID grid.13402.34, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, , Zhejiang University, ; Hangzhou, Zhejiang China
                Article
                3102
                10.1038/s41598-017-03102-3
                5459818
                © The Author(s) 2017

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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