CXCL9 associated with sustained virological response in chronic hepatitis B patients receiving peginterferon alfa-2a therapy: a pilot study
There is lack of a practical biomarker to predict sustained virological response (SVR) in chronic hepatitis B (CHB) patients undergoing peginterferon alfa-2a (PEG-IFN). The aim of this pilot study was to identify immunological features associated with SVR. Consecutive 74 CHB patients receiving 24 we...
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| Veröffentlicht in: | PloS one 2013-10, Vol.8 (10), p.e76798-e76798 |
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| creator | Lee, I-Cheng Huang, Yi-Hsiang Su, Chien-Wei Wang, Yuan-Jen Huo, Teh-Ia Lee, Kuei-Chuan Lin, Han-Chieh |
| description | There is lack of a practical biomarker to predict sustained virological response (SVR) in chronic hepatitis B (CHB) patients undergoing peginterferon alfa-2a (PEG-IFN). The aim of this pilot study was to identify immunological features associated with SVR.
Consecutive 74 CHB patients receiving 24 weeks (for hepatitis B e antigen (HBeAg)-positive) or 48 weeks (for HBeAg-negative) PEG-IFN, were prospectively enrolled. Serum HBV viral loads, hepatitis B surface antigen (HBsAg), CXCL9, IFN-γ-inducible protein 10 (IP-10), interferon-gamma (IFN-γ) and transforming growth factor beta (TGF-β) were measured at baseline and week 12. SVR was defined as HBeAg seroconversion combined with viral load |
| doi_str_mv | 10.1371/journal.pone.0076798 |
| format | Article |
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Consecutive 74 CHB patients receiving 24 weeks (for hepatitis B e antigen (HBeAg)-positive) or 48 weeks (for HBeAg-negative) PEG-IFN, were prospectively enrolled. Serum HBV viral loads, hepatitis B surface antigen (HBsAg), CXCL9, IFN-γ-inducible protein 10 (IP-10), interferon-gamma (IFN-γ) and transforming growth factor beta (TGF-β) were measured at baseline and week 12. SVR was defined as HBeAg seroconversion combined with viral load <2000 IU/mL in HBeAg-positive (n=36), and viral load <2000 IU/mL in HBeAg-negative patients (n=38) at 48 weeks after the end of treatment.
Nineteen patients (25.7%), 7 in HBeAg-positive and 12 in HBeAg-negative, achieved SVR. There were significant declines of HBV DNA, HBsAg, IP-10 and IFN-γ levels at week 12. In multivariate analysis, pre-treatment CXCL9 >80 pg/mL, HBV DNA <2.5 x 10(7) IU/mL and on-treatment HBV viral load, HBsAg decline >10% at week 12 were predictors of SVR. The performance of CXCL9 in predicting SVR was good in patients with HBV DNA <2.5 x 10(7) IU/mL, particularly in HBeAg-negative CHB cases (positive predictive value, PPV= 64.3%).
Pre-treatment CXCL9 level has the potential to select CHB patients who can respond to PEG-IFN, especially in HBeAg-negative patients with low viral loads.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0076798</identifier><identifier>PMID: 24124595</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Alanine Transaminase - blood ; Alanine Transaminase - metabolism ; Antigens ; Antiviral Agents - therapeutic use ; Bioindicators ; Biological response modifiers ; Biomarkers ; Bone morphogenetic proteins ; Care and treatment ; Chemokine CXCL9 - blood ; Chemokine CXCL9 - metabolism ; Chemokines ; Clinical medicine ; Cytokines ; Cytokines - blood ; Cytokines - metabolism ; Deoxyribonucleic acid ; DNA ; Female ; Gastroenterology ; Genotype ; Hepatitis ; Hepatitis B ; Hepatitis B e antigen ; Hepatitis B e Antigens - immunology ; Hepatitis B surface antigen ; Hepatitis B virus - genetics ; Hepatitis B virus - immunology ; Hepatitis B, Chronic - drug therapy ; Hepatitis B, Chronic - metabolism ; Hepatitis B, Chronic - virology ; Hepatology ; Hospitals ; Humans ; Immunology ; Infections ; Interferon ; Interferon-alpha - therapeutic use ; IP-10 protein ; Liver diseases ; Male ; Medicine ; Middle Aged ; Multivariate analysis ; Patients ; Pilot Projects ; Polyethylene Glycols - therapeutic use ; Prognosis ; Proteins ; Recombinant Proteins - therapeutic use ; Seroconversion ; Time Factors ; Transforming growth factor-b ; Transforming growth factors ; Treatment Outcome ; Viral antigens ; Viral Load ; γ-Interferon</subject><ispartof>PloS one, 2013-10, Vol.8 (10), p.e76798-e76798</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Lee et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Lee et al 2013 Lee et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-ef809b84fa83a5f15453ab8fb3632eea2f3f4090a1ce833a9328491c428bb04f3</citedby><cites>FETCH-LOGICAL-c692t-ef809b84fa83a5f15453ab8fb3632eea2f3f4090a1ce833a9328491c428bb04f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3790882/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3790882/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2100,2926,23865,27923,27924,53790,53792,79371,79372</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24124595$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Tillmann, Hans</contributor><creatorcontrib>Lee, I-Cheng</creatorcontrib><creatorcontrib>Huang, Yi-Hsiang</creatorcontrib><creatorcontrib>Su, Chien-Wei</creatorcontrib><creatorcontrib>Wang, Yuan-Jen</creatorcontrib><creatorcontrib>Huo, Teh-Ia</creatorcontrib><creatorcontrib>Lee, Kuei-Chuan</creatorcontrib><creatorcontrib>Lin, Han-Chieh</creatorcontrib><title>CXCL9 associated with sustained virological response in chronic hepatitis B patients receiving peginterferon alfa-2a therapy: a pilot study</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>There is lack of a practical biomarker to predict sustained virological response (SVR) in chronic hepatitis B (CHB) patients undergoing peginterferon alfa-2a (PEG-IFN). The aim of this pilot study was to identify immunological features associated with SVR.
Consecutive 74 CHB patients receiving 24 weeks (for hepatitis B e antigen (HBeAg)-positive) or 48 weeks (for HBeAg-negative) PEG-IFN, were prospectively enrolled. Serum HBV viral loads, hepatitis B surface antigen (HBsAg), CXCL9, IFN-γ-inducible protein 10 (IP-10), interferon-gamma (IFN-γ) and transforming growth factor beta (TGF-β) were measured at baseline and week 12. SVR was defined as HBeAg seroconversion combined with viral load <2000 IU/mL in HBeAg-positive (n=36), and viral load <2000 IU/mL in HBeAg-negative patients (n=38) at 48 weeks after the end of treatment.
Nineteen patients (25.7%), 7 in HBeAg-positive and 12 in HBeAg-negative, achieved SVR. There were significant declines of HBV DNA, HBsAg, IP-10 and IFN-γ levels at week 12. In multivariate analysis, pre-treatment CXCL9 >80 pg/mL, HBV DNA <2.5 x 10(7) IU/mL and on-treatment HBV viral load, HBsAg decline >10% at week 12 were predictors of SVR. The performance of CXCL9 in predicting SVR was good in patients with HBV DNA <2.5 x 10(7) IU/mL, particularly in HBeAg-negative CHB cases (positive predictive value, PPV= 64.3%).
Pre-treatment CXCL9 level has the potential to select CHB patients who can respond to PEG-IFN, especially in HBeAg-negative patients with low viral loads.</description><subject>Adult</subject><subject>Alanine Transaminase - blood</subject><subject>Alanine Transaminase - metabolism</subject><subject>Antigens</subject><subject>Antiviral Agents - therapeutic use</subject><subject>Bioindicators</subject><subject>Biological response modifiers</subject><subject>Biomarkers</subject><subject>Bone morphogenetic proteins</subject><subject>Care and treatment</subject><subject>Chemokine CXCL9 - blood</subject><subject>Chemokine CXCL9 - metabolism</subject><subject>Chemokines</subject><subject>Clinical medicine</subject><subject>Cytokines</subject><subject>Cytokines - blood</subject><subject>Cytokines - metabolism</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Female</subject><subject>Gastroenterology</subject><subject>Genotype</subject><subject>Hepatitis</subject><subject>Hepatitis B</subject><subject>Hepatitis B e antigen</subject><subject>Hepatitis B e Antigens - immunology</subject><subject>Hepatitis B surface antigen</subject><subject>Hepatitis B virus - genetics</subject><subject>Hepatitis B virus - immunology</subject><subject>Hepatitis B, Chronic - drug therapy</subject><subject>Hepatitis B, Chronic - metabolism</subject><subject>Hepatitis B, Chronic - virology</subject><subject>Hepatology</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Immunology</subject><subject>Infections</subject><subject>Interferon</subject><subject>Interferon-alpha - therapeutic use</subject><subject>IP-10 protein</subject><subject>Liver diseases</subject><subject>Male</subject><subject>Medicine</subject><subject>Middle Aged</subject><subject>Multivariate analysis</subject><subject>Patients</subject><subject>Pilot Projects</subject><subject>Polyethylene Glycols - therapeutic use</subject><subject>Prognosis</subject><subject>Proteins</subject><subject>Recombinant Proteins - therapeutic use</subject><subject>Seroconversion</subject><subject>Time Factors</subject><subject>Transforming growth factor-b</subject><subject>Transforming growth factors</subject><subject>Treatment Outcome</subject><subject>Viral antigens</subject><subject>Viral Load</subject><subject>γ-Interferon</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk8tu1DAUhiMEoqXwBggsISFYzOBbEocFUhlxqVSpEjexs04cO3HliYPtFOYZeGk8dFp1UBcoC1_ynf-Xf_sUxWOCl4TV5NW5n8MIbjn5US8xrqu6EXeKQ9IwuqgoZndvzA-KBzGeY1wyUVX3iwPKCeVlUx4Wv1ffV6cNghi9spB0h37aNKA4xwR2zMsLG7zzvVXgUNAxu0WN7IjUEPxoFRr0BMkmG9FbtJ3pMcUMKm0v7NijSfd2TDoYnXEEzsCCAkqDDjBtXiNAk3U-oZjmbvOwuGfARf1oNx4VX9-_-7L6uDg9-3CyOj5dqKqhaaGNwE0ruAHBoDSk5CWDVpiWVYxqDdQww3GDgSgtGIMcguANUZyKtsXcsKPi6aXu5HyUuxyjzDnVlHFW4kycXBKdh3M5BbuGsJEerPy74UMvISSrnJa0MbQkZUdaUmUX2nRldqtLTlRFCOFZ683ObW7XulM5oABuT3T_z2gH2fsLyeoGC0GzwIudQPA_Zh2TXNuotHMwaj9HSThnnFaCkIw--we9_XQ7qod8ADsan33VVlQe81pwWtY50qNieQuVv06vrcqPzti8v1fwcq8gM0n_Sj3MMcqTz5_-nz37ts8-v8EOGlwaondzsvkt7oP8ElTBxxi0uQ6ZYLntmas05LZn5K5nctmTmxd0XXTVJOwP-PAR7w</recordid><startdate>20131004</startdate><enddate>20131004</enddate><creator>Lee, I-Cheng</creator><creator>Huang, Yi-Hsiang</creator><creator>Su, Chien-Wei</creator><creator>Wang, Yuan-Jen</creator><creator>Huo, Teh-Ia</creator><creator>Lee, Kuei-Chuan</creator><creator>Lin, Han-Chieh</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20131004</creationdate><title>CXCL9 associated with sustained virological response in chronic hepatitis B patients receiving peginterferon alfa-2a therapy: a pilot study</title><author>Lee, I-Cheng ; Huang, Yi-Hsiang ; Su, Chien-Wei ; Wang, Yuan-Jen ; Huo, Teh-Ia ; Lee, Kuei-Chuan ; Lin, Han-Chieh</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-ef809b84fa83a5f15453ab8fb3632eea2f3f4090a1ce833a9328491c428bb04f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult</topic><topic>Alanine Transaminase - blood</topic><topic>Alanine Transaminase - metabolism</topic><topic>Antigens</topic><topic>Antiviral Agents - therapeutic use</topic><topic>Bioindicators</topic><topic>Biological response modifiers</topic><topic>Biomarkers</topic><topic>Bone morphogenetic proteins</topic><topic>Care and treatment</topic><topic>Chemokine CXCL9 - blood</topic><topic>Chemokine CXCL9 - metabolism</topic><topic>Chemokines</topic><topic>Clinical medicine</topic><topic>Cytokines</topic><topic>Cytokines - blood</topic><topic>Cytokines - metabolism</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Female</topic><topic>Gastroenterology</topic><topic>Genotype</topic><topic>Hepatitis</topic><topic>Hepatitis B</topic><topic>Hepatitis B e antigen</topic><topic>Hepatitis B e Antigens - immunology</topic><topic>Hepatitis B surface antigen</topic><topic>Hepatitis B virus - genetics</topic><topic>Hepatitis B virus - immunology</topic><topic>Hepatitis B, Chronic - drug therapy</topic><topic>Hepatitis B, Chronic - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, I-Cheng</au><au>Huang, Yi-Hsiang</au><au>Su, Chien-Wei</au><au>Wang, Yuan-Jen</au><au>Huo, Teh-Ia</au><au>Lee, Kuei-Chuan</au><au>Lin, Han-Chieh</au><au>Tillmann, Hans</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CXCL9 associated with sustained virological response in chronic hepatitis B patients receiving peginterferon alfa-2a therapy: a pilot study</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-10-04</date><risdate>2013</risdate><volume>8</volume><issue>10</issue><spage>e76798</spage><epage>e76798</epage><pages>e76798-e76798</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>There is lack of a practical biomarker to predict sustained virological response (SVR) in chronic hepatitis B (CHB) patients undergoing peginterferon alfa-2a (PEG-IFN). The aim of this pilot study was to identify immunological features associated with SVR.
Consecutive 74 CHB patients receiving 24 weeks (for hepatitis B e antigen (HBeAg)-positive) or 48 weeks (for HBeAg-negative) PEG-IFN, were prospectively enrolled. Serum HBV viral loads, hepatitis B surface antigen (HBsAg), CXCL9, IFN-γ-inducible protein 10 (IP-10), interferon-gamma (IFN-γ) and transforming growth factor beta (TGF-β) were measured at baseline and week 12. SVR was defined as HBeAg seroconversion combined with viral load <2000 IU/mL in HBeAg-positive (n=36), and viral load <2000 IU/mL in HBeAg-negative patients (n=38) at 48 weeks after the end of treatment.
Nineteen patients (25.7%), 7 in HBeAg-positive and 12 in HBeAg-negative, achieved SVR. There were significant declines of HBV DNA, HBsAg, IP-10 and IFN-γ levels at week 12. In multivariate analysis, pre-treatment CXCL9 >80 pg/mL, HBV DNA <2.5 x 10(7) IU/mL and on-treatment HBV viral load, HBsAg decline >10% at week 12 were predictors of SVR. The performance of CXCL9 in predicting SVR was good in patients with HBV DNA <2.5 x 10(7) IU/mL, particularly in HBeAg-negative CHB cases (positive predictive value, PPV= 64.3%).
Pre-treatment CXCL9 level has the potential to select CHB patients who can respond to PEG-IFN, especially in HBeAg-negative patients with low viral loads.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24124595</pmid><doi>10.1371/journal.pone.0076798</doi><tpages>e76798</tpages><oa>free_for_read</oa></addata></record> |
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| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2037234350 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adult Alanine Transaminase - blood Alanine Transaminase - metabolism Antigens Antiviral Agents - therapeutic use Bioindicators Biological response modifiers Biomarkers Bone morphogenetic proteins Care and treatment Chemokine CXCL9 - blood Chemokine CXCL9 - metabolism Chemokines Clinical medicine Cytokines Cytokines - blood Cytokines - metabolism Deoxyribonucleic acid DNA Female Gastroenterology Genotype Hepatitis Hepatitis B Hepatitis B e antigen Hepatitis B e Antigens - immunology Hepatitis B surface antigen Hepatitis B virus - genetics Hepatitis B virus - immunology Hepatitis B, Chronic - drug therapy Hepatitis B, Chronic - metabolism Hepatitis B, Chronic - virology Hepatology Hospitals Humans Immunology Infections Interferon Interferon-alpha - therapeutic use IP-10 protein Liver diseases Male Medicine Middle Aged Multivariate analysis Patients Pilot Projects Polyethylene Glycols - therapeutic use Prognosis Proteins Recombinant Proteins - therapeutic use Seroconversion Time Factors Transforming growth factor-b Transforming growth factors Treatment Outcome Viral antigens Viral Load γ-Interferon |
| title | CXCL9 associated with sustained virological response in chronic hepatitis B patients receiving peginterferon alfa-2a therapy: a pilot study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-11T18%3A07%3A35IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=CXCL9%20associated%20with%20sustained%20virological%20response%20in%20chronic%20hepatitis%20B%20patients%20receiving%20peginterferon%20alfa-2a%20therapy:%20a%20pilot%20study&rft.jtitle=PloS%20one&rft.au=Lee,%20I-Cheng&rft.date=2013-10-04&rft.volume=8&rft.issue=10&rft.spage=e76798&rft.epage=e76798&rft.pages=e76798-e76798&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0076798&rft_dat=%3Cgale_plos_%3EA478425745%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2037234350&rft_id=info:pmid/24124595&rft_galeid=A478425745&rft_doaj_id=oai_doaj_org_article_29f2515d1b1649129d58497541c61114&rfr_iscdi=true |