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Significant histological disease of patients with chronic hepatitis B virus infection in the grey zone

Summary Background Many patients with chronic hepatitis B (CHB) do not meet the definitions of the traditional natural phases and are classified as being in the grey zone (GZ). Aims To investigate liver histology, and to establish a management strategy for patients with CHB in the GZ. Methods This s...

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Published in:Alimentary pharmacology & therapeutics 2023-03, Vol.57 (5), p.464-474
Main Authors: Wang, Jian, Yan, Xiaomin, Zhu, Li, Liu, Jiacheng, Qiu, Yuanwang, Li, Yiguang, Liu, Yilin, Xue, Ruifei, Zhan, Jie, Jiang, Suling, Geng, Yu, Wan, Yawen, Li, Ming, Mao, Minxin, Gao, Dongmei, Yin, Shengxia, Tong, Xin, Xia, Juan, Ding, Weimao, Chen, Yuxin, Li, Jie, Zhu, Chuanwu, Huang, Rui, Wu, Chao
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cited_by cdi_FETCH-LOGICAL-c3532-958ee3ba7704c7caba9115fdd2319c954591dcb668c493922a971c64dca023ea3
cites cdi_FETCH-LOGICAL-c3532-958ee3ba7704c7caba9115fdd2319c954591dcb668c493922a971c64dca023ea3
container_end_page 474
container_issue 5
container_start_page 464
container_title Alimentary pharmacology & therapeutics
container_volume 57
creator Wang, Jian
Yan, Xiaomin
Zhu, Li
Liu, Jiacheng
Qiu, Yuanwang
Li, Yiguang
Liu, Yilin
Xue, Ruifei
Zhan, Jie
Jiang, Suling
Geng, Yu
Wan, Yawen
Li, Ming
Mao, Minxin
Gao, Dongmei
Yin, Shengxia
Tong, Xin
Xia, Juan
Ding, Weimao
Chen, Yuxin
Li, Jie
Zhu, Chuanwu
Huang, Rui
Wu, Chao
description Summary Background Many patients with chronic hepatitis B (CHB) do not meet the definitions of the traditional natural phases and are classified as being in the grey zone (GZ). Aims To investigate liver histology, and to establish a management strategy for patients with CHB in the GZ. Methods This study included 1043 patients with CHB who underwent liver biopsy. Phases of natural history were determined according to the AASLD 2018 hepatitis B guidance. CHB patients in the GZ were divided into HBeAg‐positive, normal ALT and HBV DNA ≤106 IU/ml (GZ‐A); HBeAg‐positive, elevated ALT and HBV DNA ≤2 × 104 IU/ml (GZ‐B); HBeAg‐negative, normal ALT and HBV DNA ≥2 × 103 IU/ml (GZ‐C) and HBeAg‐negative, elevated ALT and HBV DNA ≤2 × 103 IU/ml (GZ‐D). Significant histological disease was defined as liver inflammation ≥G2 and/or liver fibrosis ≥S2. Results Two hundred and forty two (23.2%) patients were in the GZ. Approximately 72.7% had significant histological disease. HBeAg‐positive GZ CHB patients had a higher proportion of significant histological disease than HBeAg‐negative GZ patients (91.1% vs. 68.5%, p = 0.002). GZ‐D (42.6%) was the dominant category, followed by GZ‐C (38.8%), GZ‐A (10.3%) and GZ‐B (8.3%). The highest proportion of significant histological disease was observed patients in GZ‐B (100.0%), followed by GZ‐A (84.0%), GZ‐D (69.9%) and GZ‐C (67.0%). Prothrombin time (PT) was an independent risk factor of significant histological disease in the HBeAg‐negative GZ. Conclusions Over 70% of GZ CHB patients had significant histological disease. We recommend antiviral treatment for HBeAg‐positive and HBeAg‐negative GZ CHB patients with high PT. Nearly a quarter of patients with CHB were in the grey zone (GZ), and 72.7% of GZ CHB patients had significant histologic disease. HBeAg‐positive GZ CHB patients and HBeAg‐negative GZ CHB patients with high prothrombin timeare recommended to receive antiviral treatment.
doi_str_mv 10.1111/apt.17272
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Aims To investigate liver histology, and to establish a management strategy for patients with CHB in the GZ. Methods This study included 1043 patients with CHB who underwent liver biopsy. Phases of natural history were determined according to the AASLD 2018 hepatitis B guidance. CHB patients in the GZ were divided into HBeAg‐positive, normal ALT and HBV DNA ≤106 IU/ml (GZ‐A); HBeAg‐positive, elevated ALT and HBV DNA ≤2 × 104 IU/ml (GZ‐B); HBeAg‐negative, normal ALT and HBV DNA ≥2 × 103 IU/ml (GZ‐C) and HBeAg‐negative, elevated ALT and HBV DNA ≤2 × 103 IU/ml (GZ‐D). Significant histological disease was defined as liver inflammation ≥G2 and/or liver fibrosis ≥S2. Results Two hundred and forty two (23.2%) patients were in the GZ. Approximately 72.7% had significant histological disease. HBeAg‐positive GZ CHB patients had a higher proportion of significant histological disease than HBeAg‐negative GZ patients (91.1% vs. 68.5%, p = 0.002). GZ‐D (42.6%) was the dominant category, followed by GZ‐C (38.8%), GZ‐A (10.3%) and GZ‐B (8.3%). The highest proportion of significant histological disease was observed patients in GZ‐B (100.0%), followed by GZ‐A (84.0%), GZ‐D (69.9%) and GZ‐C (67.0%). Prothrombin time (PT) was an independent risk factor of significant histological disease in the HBeAg‐negative GZ. Conclusions Over 70% of GZ CHB patients had significant histological disease. We recommend antiviral treatment for HBeAg‐positive and HBeAg‐negative GZ CHB patients with high PT. Nearly a quarter of patients with CHB were in the grey zone (GZ), and 72.7% of GZ CHB patients had significant histologic disease. HBeAg‐positive GZ CHB patients and HBeAg‐negative GZ CHB patients with high prothrombin timeare recommended to receive antiviral treatment.</description><identifier>ISSN: 0269-2813</identifier><identifier>EISSN: 1365-2036</identifier><identifier>DOI: 10.1111/apt.17272</identifier><identifier>PMID: 36324235</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Alanine Transaminase ; Biopsy ; Chronic infection ; Deoxyribonucleic acid ; DNA ; DNA, Viral ; Fibrosis ; Hepatitis B ; Hepatitis B e antigen ; Hepatitis B e Antigens ; Hepatitis B virus - genetics ; Hepatitis B, Chronic - pathology ; Humans ; Interferon ; Liver ; Liver diseases ; Prothrombin ; Risk factors</subject><ispartof>Alimentary pharmacology &amp; therapeutics, 2023-03, Vol.57 (5), p.464-474</ispartof><rights>2022 John Wiley &amp; Sons Ltd.</rights><rights>Copyright © 2023 John Wiley &amp; Sons Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3532-958ee3ba7704c7caba9115fdd2319c954591dcb668c493922a971c64dca023ea3</citedby><cites>FETCH-LOGICAL-c3532-958ee3ba7704c7caba9115fdd2319c954591dcb668c493922a971c64dca023ea3</cites><orcidid>0000-0002-0953-5912 ; 0000-0002-1657-010X ; 0000-0002-3189-7960 ; 0000-0003-0973-8645</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36324235$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Jian</creatorcontrib><creatorcontrib>Yan, Xiaomin</creatorcontrib><creatorcontrib>Zhu, Li</creatorcontrib><creatorcontrib>Liu, Jiacheng</creatorcontrib><creatorcontrib>Qiu, Yuanwang</creatorcontrib><creatorcontrib>Li, Yiguang</creatorcontrib><creatorcontrib>Liu, Yilin</creatorcontrib><creatorcontrib>Xue, Ruifei</creatorcontrib><creatorcontrib>Zhan, Jie</creatorcontrib><creatorcontrib>Jiang, Suling</creatorcontrib><creatorcontrib>Geng, Yu</creatorcontrib><creatorcontrib>Wan, Yawen</creatorcontrib><creatorcontrib>Li, Ming</creatorcontrib><creatorcontrib>Mao, Minxin</creatorcontrib><creatorcontrib>Gao, Dongmei</creatorcontrib><creatorcontrib>Yin, Shengxia</creatorcontrib><creatorcontrib>Tong, Xin</creatorcontrib><creatorcontrib>Xia, Juan</creatorcontrib><creatorcontrib>Ding, Weimao</creatorcontrib><creatorcontrib>Chen, Yuxin</creatorcontrib><creatorcontrib>Li, Jie</creatorcontrib><creatorcontrib>Zhu, Chuanwu</creatorcontrib><creatorcontrib>Huang, Rui</creatorcontrib><creatorcontrib>Wu, Chao</creatorcontrib><title>Significant histological disease of patients with chronic hepatitis B virus infection in the grey zone</title><title>Alimentary pharmacology &amp; therapeutics</title><addtitle>Aliment Pharmacol Ther</addtitle><description>Summary Background Many patients with chronic hepatitis B (CHB) do not meet the definitions of the traditional natural phases and are classified as being in the grey zone (GZ). Aims To investigate liver histology, and to establish a management strategy for patients with CHB in the GZ. Methods This study included 1043 patients with CHB who underwent liver biopsy. Phases of natural history were determined according to the AASLD 2018 hepatitis B guidance. CHB patients in the GZ were divided into HBeAg‐positive, normal ALT and HBV DNA ≤106 IU/ml (GZ‐A); HBeAg‐positive, elevated ALT and HBV DNA ≤2 × 104 IU/ml (GZ‐B); HBeAg‐negative, normal ALT and HBV DNA ≥2 × 103 IU/ml (GZ‐C) and HBeAg‐negative, elevated ALT and HBV DNA ≤2 × 103 IU/ml (GZ‐D). Significant histological disease was defined as liver inflammation ≥G2 and/or liver fibrosis ≥S2. Results Two hundred and forty two (23.2%) patients were in the GZ. Approximately 72.7% had significant histological disease. HBeAg‐positive GZ CHB patients had a higher proportion of significant histological disease than HBeAg‐negative GZ patients (91.1% vs. 68.5%, p = 0.002). GZ‐D (42.6%) was the dominant category, followed by GZ‐C (38.8%), GZ‐A (10.3%) and GZ‐B (8.3%). The highest proportion of significant histological disease was observed patients in GZ‐B (100.0%), followed by GZ‐A (84.0%), GZ‐D (69.9%) and GZ‐C (67.0%). Prothrombin time (PT) was an independent risk factor of significant histological disease in the HBeAg‐negative GZ. Conclusions Over 70% of GZ CHB patients had significant histological disease. We recommend antiviral treatment for HBeAg‐positive and HBeAg‐negative GZ CHB patients with high PT. Nearly a quarter of patients with CHB were in the grey zone (GZ), and 72.7% of GZ CHB patients had significant histologic disease. HBeAg‐positive GZ CHB patients and HBeAg‐negative GZ CHB patients with high prothrombin timeare recommended to receive antiviral treatment.</description><subject>Alanine Transaminase</subject><subject>Biopsy</subject><subject>Chronic infection</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA, Viral</subject><subject>Fibrosis</subject><subject>Hepatitis B</subject><subject>Hepatitis B e antigen</subject><subject>Hepatitis B e Antigens</subject><subject>Hepatitis B virus - genetics</subject><subject>Hepatitis B, Chronic - pathology</subject><subject>Humans</subject><subject>Interferon</subject><subject>Liver</subject><subject>Liver diseases</subject><subject>Prothrombin</subject><subject>Risk factors</subject><issn>0269-2813</issn><issn>1365-2036</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp1kF1LHDEUhkOp6Lr1on-gBHpTL0bzMUkmlyp-gaBQez1kM2d2IrPJNslU1l9vtmt7IXhuzgcPL4cHoa-UnNBSp2adT6hiin1CM8qlqBjh8jOaESZ1xRrKD9BhSk-EEKkI20cHXHJWMy5mqP_plt71zhqf8eBSDmNYlm3EnUtgEuDQ47XJDnxO-NnlAdshBu8sHmB7zy7hc_zHxSlh53uw2QVfJpwHwMsIG_wSPHxBe70ZExy99Tn6dXX5eHFT3d1f316c3VWWC84qLRoAvjBKkdoqaxZGUyr6rmOcaqtFLTTt7ELKxtaaa8aMVtTKurOGMA6Gz9GPXe46ht8TpNyuXLIwjsZDmFLLFC-iaNOIgn5_hz6FKfryXaGU0IzWkhXqeEfZGFKK0Lfr6FYmblpK2q38tshv_8ov7Le3xGmxgu4_-c92AU53wLMbYfNxUnv28LiLfAUkHY4x</recordid><startdate>202303</startdate><enddate>202303</enddate><creator>Wang, Jian</creator><creator>Yan, Xiaomin</creator><creator>Zhu, Li</creator><creator>Liu, Jiacheng</creator><creator>Qiu, Yuanwang</creator><creator>Li, Yiguang</creator><creator>Liu, Yilin</creator><creator>Xue, Ruifei</creator><creator>Zhan, Jie</creator><creator>Jiang, Suling</creator><creator>Geng, Yu</creator><creator>Wan, Yawen</creator><creator>Li, Ming</creator><creator>Mao, Minxin</creator><creator>Gao, Dongmei</creator><creator>Yin, Shengxia</creator><creator>Tong, Xin</creator><creator>Xia, Juan</creator><creator>Ding, Weimao</creator><creator>Chen, Yuxin</creator><creator>Li, Jie</creator><creator>Zhu, Chuanwu</creator><creator>Huang, Rui</creator><creator>Wu, Chao</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TK</scope><scope>7U9</scope><scope>H94</scope><scope>M7N</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-0953-5912</orcidid><orcidid>https://orcid.org/0000-0002-1657-010X</orcidid><orcidid>https://orcid.org/0000-0002-3189-7960</orcidid><orcidid>https://orcid.org/0000-0003-0973-8645</orcidid></search><sort><creationdate>202303</creationdate><title>Significant histological disease of patients with chronic hepatitis B virus infection in the grey zone</title><author>Wang, Jian ; Yan, Xiaomin ; Zhu, Li ; Liu, Jiacheng ; Qiu, Yuanwang ; Li, Yiguang ; Liu, Yilin ; Xue, Ruifei ; Zhan, Jie ; Jiang, Suling ; Geng, Yu ; Wan, Yawen ; Li, Ming ; Mao, Minxin ; Gao, Dongmei ; Yin, Shengxia ; Tong, Xin ; Xia, Juan ; Ding, Weimao ; Chen, Yuxin ; Li, Jie ; Zhu, Chuanwu ; Huang, Rui ; Wu, Chao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3532-958ee3ba7704c7caba9115fdd2319c954591dcb668c493922a971c64dca023ea3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Alanine Transaminase</topic><topic>Biopsy</topic><topic>Chronic infection</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA, Viral</topic><topic>Fibrosis</topic><topic>Hepatitis B</topic><topic>Hepatitis B e antigen</topic><topic>Hepatitis B e Antigens</topic><topic>Hepatitis B virus - genetics</topic><topic>Hepatitis B, Chronic - pathology</topic><topic>Humans</topic><topic>Interferon</topic><topic>Liver</topic><topic>Liver diseases</topic><topic>Prothrombin</topic><topic>Risk factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Jian</creatorcontrib><creatorcontrib>Yan, Xiaomin</creatorcontrib><creatorcontrib>Zhu, Li</creatorcontrib><creatorcontrib>Liu, Jiacheng</creatorcontrib><creatorcontrib>Qiu, Yuanwang</creatorcontrib><creatorcontrib>Li, Yiguang</creatorcontrib><creatorcontrib>Liu, Yilin</creatorcontrib><creatorcontrib>Xue, Ruifei</creatorcontrib><creatorcontrib>Zhan, Jie</creatorcontrib><creatorcontrib>Jiang, Suling</creatorcontrib><creatorcontrib>Geng, Yu</creatorcontrib><creatorcontrib>Wan, Yawen</creatorcontrib><creatorcontrib>Li, Ming</creatorcontrib><creatorcontrib>Mao, Minxin</creatorcontrib><creatorcontrib>Gao, Dongmei</creatorcontrib><creatorcontrib>Yin, Shengxia</creatorcontrib><creatorcontrib>Tong, Xin</creatorcontrib><creatorcontrib>Xia, Juan</creatorcontrib><creatorcontrib>Ding, Weimao</creatorcontrib><creatorcontrib>Chen, Yuxin</creatorcontrib><creatorcontrib>Li, Jie</creatorcontrib><creatorcontrib>Zhu, Chuanwu</creatorcontrib><creatorcontrib>Huang, Rui</creatorcontrib><creatorcontrib>Wu, Chao</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>MEDLINE - Academic</collection><jtitle>Alimentary pharmacology &amp; therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Jian</au><au>Yan, Xiaomin</au><au>Zhu, Li</au><au>Liu, Jiacheng</au><au>Qiu, Yuanwang</au><au>Li, Yiguang</au><au>Liu, Yilin</au><au>Xue, Ruifei</au><au>Zhan, Jie</au><au>Jiang, Suling</au><au>Geng, Yu</au><au>Wan, Yawen</au><au>Li, Ming</au><au>Mao, Minxin</au><au>Gao, Dongmei</au><au>Yin, Shengxia</au><au>Tong, Xin</au><au>Xia, Juan</au><au>Ding, Weimao</au><au>Chen, Yuxin</au><au>Li, Jie</au><au>Zhu, Chuanwu</au><au>Huang, Rui</au><au>Wu, Chao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Significant histological disease of patients with chronic hepatitis B virus infection in the grey zone</atitle><jtitle>Alimentary pharmacology &amp; therapeutics</jtitle><addtitle>Aliment Pharmacol Ther</addtitle><date>2023-03</date><risdate>2023</risdate><volume>57</volume><issue>5</issue><spage>464</spage><epage>474</epage><pages>464-474</pages><issn>0269-2813</issn><eissn>1365-2036</eissn><abstract>Summary Background Many patients with chronic hepatitis B (CHB) do not meet the definitions of the traditional natural phases and are classified as being in the grey zone (GZ). Aims To investigate liver histology, and to establish a management strategy for patients with CHB in the GZ. Methods This study included 1043 patients with CHB who underwent liver biopsy. Phases of natural history were determined according to the AASLD 2018 hepatitis B guidance. CHB patients in the GZ were divided into HBeAg‐positive, normal ALT and HBV DNA ≤106 IU/ml (GZ‐A); HBeAg‐positive, elevated ALT and HBV DNA ≤2 × 104 IU/ml (GZ‐B); HBeAg‐negative, normal ALT and HBV DNA ≥2 × 103 IU/ml (GZ‐C) and HBeAg‐negative, elevated ALT and HBV DNA ≤2 × 103 IU/ml (GZ‐D). Significant histological disease was defined as liver inflammation ≥G2 and/or liver fibrosis ≥S2. Results Two hundred and forty two (23.2%) patients were in the GZ. Approximately 72.7% had significant histological disease. HBeAg‐positive GZ CHB patients had a higher proportion of significant histological disease than HBeAg‐negative GZ patients (91.1% vs. 68.5%, p = 0.002). GZ‐D (42.6%) was the dominant category, followed by GZ‐C (38.8%), GZ‐A (10.3%) and GZ‐B (8.3%). The highest proportion of significant histological disease was observed patients in GZ‐B (100.0%), followed by GZ‐A (84.0%), GZ‐D (69.9%) and GZ‐C (67.0%). Prothrombin time (PT) was an independent risk factor of significant histological disease in the HBeAg‐negative GZ. Conclusions Over 70% of GZ CHB patients had significant histological disease. We recommend antiviral treatment for HBeAg‐positive and HBeAg‐negative GZ CHB patients with high PT. Nearly a quarter of patients with CHB were in the grey zone (GZ), and 72.7% of GZ CHB patients had significant histologic disease. HBeAg‐positive GZ CHB patients and HBeAg‐negative GZ CHB patients with high prothrombin timeare recommended to receive antiviral treatment.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>36324235</pmid><doi>10.1111/apt.17272</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-0953-5912</orcidid><orcidid>https://orcid.org/0000-0002-1657-010X</orcidid><orcidid>https://orcid.org/0000-0002-3189-7960</orcidid><orcidid>https://orcid.org/0000-0003-0973-8645</orcidid></addata></record>
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subjects Alanine Transaminase
Biopsy
Chronic infection
Deoxyribonucleic acid
DNA
DNA, Viral
Fibrosis
Hepatitis B
Hepatitis B e antigen
Hepatitis B e Antigens
Hepatitis B virus - genetics
Hepatitis B, Chronic - pathology
Humans
Interferon
Liver
Liver diseases
Prothrombin
Risk factors
title Significant histological disease of patients with chronic hepatitis B virus infection in the grey zone
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