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High serum IL-21 levels after 12 weeks of antiviral therapy predict HBeAg seroconversion in chronic hepatitis B
Background & Aims Interleukin-21 (IL-21) stimulates T cell and B cell responses and plays a role in control of chronic viral infections. The role of IL-21 in chronic hepatitis B virus (HBV) infection is not understood. Methods Serum IL-21 levels were measured by enzyme immunoassay in 75 HBeAg-po...
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| Published in: | Journal of hepatology 2012-04, Vol.56 (4), p.775-781 |
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| creator | Ma, Shi-Wu Huang, Xuan Li, Yong-Yin Tang, Li-Bo Sun, Xiao-Feng Jiang, Xiao-Tao Zhang, Yue-Xin Sun, Jian Liu, Zhi-Hua Abbott, William G.H Dong, Yu-Hong Naoumov, Nikolai V Hou, Jin-Lin |
| description | Background & Aims Interleukin-21 (IL-21) stimulates T cell and B cell responses and plays a role in control of chronic viral infections. The role of IL-21 in chronic hepatitis B virus (HBV) infection is not understood. Methods Serum IL-21 levels were measured by enzyme immunoassay in 75 HBeAg-positive chronic hepatitis B (CHB) patients undergoing telbivudine treatment. The findings were validated in 103 patients from a separate clinical trial of telbivudine. A complete response to telbivudine was defined as having both HBeAg seroconversion and serum HBV-DNA level |
| doi_str_mv | 10.1016/j.jhep.2011.10.020 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_929121222</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>1_s2_0_S0168827811008580</els_id><sourcerecordid>929121222</sourcerecordid><originalsourceid>FETCH-LOGICAL-c387t-742d737e46ec164eb95b8660704a3de2da7461d61bff8f8b58a1b65e118b3b13</originalsourceid><addsrcrecordid>eNpFkcFu1DAQhi0EotvCC3BAviBOWWacxPFekNoKupVW4kDvluNMuk6zcbCTRfv2ONoFTiONvvk18w1jHxDWCCi_dOtuT-NaAGJqrEHAK7ZCCZCBLPA1WyVIZUpU6opdx9gBQA6b4i27EgKrHMtixfzWPe95pDAf-OMuE8h7OlIfuWknChwF_030ErlvuRkmd3TB9HzaUzDjiY-BGmcnvr2j2-clxFs_HClE5wfuBm73wQ_O8rSlmdzkIr97x960po_0_lJv2NP3b0_322z34-Hx_naX2VxVU1YVoqnyigpJFmVB9aaslZRQQWHyhkRjqkJiI7FuW9WqulQGa1kSoqrzGvMb9vkcOwb_a6Y46YOLlvreDOTnqDdigwKFEIkUZ9IGH2OgVo_BHUw4aQS9aNadXjTrRfPSS5rT0MdL_FwfqPk38tdrAj5dABOt6dtgBuvif66U6cxyCfp65pJyOjoK2vYuKTP9C50odn4OQ9KkUUehQf9cPro8FBFAlQryP6cQmuw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>929121222</pqid></control><display><type>article</type><title>High serum IL-21 levels after 12 weeks of antiviral therapy predict HBeAg seroconversion in chronic hepatitis B</title><source>ScienceDirect Freedom Collection</source><creator>Ma, Shi-Wu ; Huang, Xuan ; Li, Yong-Yin ; Tang, Li-Bo ; Sun, Xiao-Feng ; Jiang, Xiao-Tao ; Zhang, Yue-Xin ; Sun, Jian ; Liu, Zhi-Hua ; Abbott, William G.H ; Dong, Yu-Hong ; Naoumov, Nikolai V ; Hou, Jin-Lin</creator><creatorcontrib>Ma, Shi-Wu ; Huang, Xuan ; Li, Yong-Yin ; Tang, Li-Bo ; Sun, Xiao-Feng ; Jiang, Xiao-Tao ; Zhang, Yue-Xin ; Sun, Jian ; Liu, Zhi-Hua ; Abbott, William G.H ; Dong, Yu-Hong ; Naoumov, Nikolai V ; Hou, Jin-Lin</creatorcontrib><description>Background & Aims Interleukin-21 (IL-21) stimulates T cell and B cell responses and plays a role in control of chronic viral infections. The role of IL-21 in chronic hepatitis B virus (HBV) infection is not understood. Methods Serum IL-21 levels were measured by enzyme immunoassay in 75 HBeAg-positive chronic hepatitis B (CHB) patients undergoing telbivudine treatment. The findings were validated in 103 patients from a separate clinical trial of telbivudine. A complete response to telbivudine was defined as having both HBeAg seroconversion and serum HBV-DNA level <300 copies/ml by treatment week 52. The proportions of T-cells producing IL-21 and/or expressing programmed death 1 (PD-1) in peripheral blood mononuclear cells were assessed longitudinally during treatment by intracellular cytokine staining and flow cytometry. Results Median serum IL-21 levels at treatment week 12 were significantly higher in patients who did achieve vs. patients who did not achieve a complete response in both the initial (128.4 vs. 69.2 pg/ml, p = 0.003) and the validation (142.2 vs. 89.9 pg/ml, p = 0.004) trials. Serum levels of IL-21 ( p = 0.005) or HBV-DNA ( p = 0.003) levels at treatment week 12 independently predicted HBeAg seroconversion in the first year of treatment. The decrease in PD-1 expression on CD4+ and CD8+ T cells during the first 12 weeks on telbivudine treatment was not correlated with changes in IL-21 concentrations. Conclusions Serum IL-21 levels may be a biomarker for HBeAg seroconversion, and may contribute to individualization of antiviral therapy in HBeAg-positive CHB. IL-21 may also have a role in immunotherapy for CHB.</description><identifier>ISSN: 0168-8278</identifier><identifier>EISSN: 1600-0641</identifier><identifier>DOI: 10.1016/j.jhep.2011.10.020</identifier><identifier>PMID: 22173154</identifier><identifier>CODEN: JOHEEC</identifier><language>eng</language><publisher>Kidlington: Elsevier</publisher><subject>Adult ; Alanine Transaminase - blood ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antiviral agents ; Antiviral Agents - therapeutic use ; Biological and medical sciences ; Biomarkers - blood ; Disease Progression ; DNA, Viral - blood ; Female ; Gastroenterology and Hepatology ; Gastroenterology. Liver. Pancreas. Abdomen ; Hepatitis B e Antigens - blood ; Hepatitis B virus - genetics ; Hepatitis B, Chronic - diagnosis ; Hepatitis B, Chronic - drug therapy ; Hepatitis B, Chronic - immunology ; Human viral diseases ; Humans ; Infectious diseases ; Interleukins - blood ; Male ; Medical sciences ; Nucleosides - therapeutic use ; Pharmacology. Drug treatments ; Pyrimidinones - therapeutic use ; Reproducibility of Results ; Sensitivity and Specificity ; Severity of Illness Index ; Thymidine - analogs & derivatives ; Treatment Outcome ; Viral diseases ; Viral hepatitis</subject><ispartof>Journal of hepatology, 2012-04, Vol.56 (4), p.775-781</ispartof><rights>European Association for the Study of the Liver</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c387t-742d737e46ec164eb95b8660704a3de2da7461d61bff8f8b58a1b65e118b3b13</citedby><cites>FETCH-LOGICAL-c387t-742d737e46ec164eb95b8660704a3de2da7461d61bff8f8b58a1b65e118b3b13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25638750$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22173154$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ma, Shi-Wu</creatorcontrib><creatorcontrib>Huang, Xuan</creatorcontrib><creatorcontrib>Li, Yong-Yin</creatorcontrib><creatorcontrib>Tang, Li-Bo</creatorcontrib><creatorcontrib>Sun, Xiao-Feng</creatorcontrib><creatorcontrib>Jiang, Xiao-Tao</creatorcontrib><creatorcontrib>Zhang, Yue-Xin</creatorcontrib><creatorcontrib>Sun, Jian</creatorcontrib><creatorcontrib>Liu, Zhi-Hua</creatorcontrib><creatorcontrib>Abbott, William G.H</creatorcontrib><creatorcontrib>Dong, Yu-Hong</creatorcontrib><creatorcontrib>Naoumov, Nikolai V</creatorcontrib><creatorcontrib>Hou, Jin-Lin</creatorcontrib><title>High serum IL-21 levels after 12 weeks of antiviral therapy predict HBeAg seroconversion in chronic hepatitis B</title><title>Journal of hepatology</title><addtitle>J Hepatol</addtitle><description>Background & Aims Interleukin-21 (IL-21) stimulates T cell and B cell responses and plays a role in control of chronic viral infections. The role of IL-21 in chronic hepatitis B virus (HBV) infection is not understood. Methods Serum IL-21 levels were measured by enzyme immunoassay in 75 HBeAg-positive chronic hepatitis B (CHB) patients undergoing telbivudine treatment. The findings were validated in 103 patients from a separate clinical trial of telbivudine. A complete response to telbivudine was defined as having both HBeAg seroconversion and serum HBV-DNA level <300 copies/ml by treatment week 52. The proportions of T-cells producing IL-21 and/or expressing programmed death 1 (PD-1) in peripheral blood mononuclear cells were assessed longitudinally during treatment by intracellular cytokine staining and flow cytometry. Results Median serum IL-21 levels at treatment week 12 were significantly higher in patients who did achieve vs. patients who did not achieve a complete response in both the initial (128.4 vs. 69.2 pg/ml, p = 0.003) and the validation (142.2 vs. 89.9 pg/ml, p = 0.004) trials. Serum levels of IL-21 ( p = 0.005) or HBV-DNA ( p = 0.003) levels at treatment week 12 independently predicted HBeAg seroconversion in the first year of treatment. The decrease in PD-1 expression on CD4+ and CD8+ T cells during the first 12 weeks on telbivudine treatment was not correlated with changes in IL-21 concentrations. Conclusions Serum IL-21 levels may be a biomarker for HBeAg seroconversion, and may contribute to individualization of antiviral therapy in HBeAg-positive CHB. IL-21 may also have a role in immunotherapy for CHB.</description><subject>Adult</subject><subject>Alanine Transaminase - blood</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antiviral agents</subject><subject>Antiviral Agents - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - blood</subject><subject>Disease Progression</subject><subject>DNA, Viral - blood</subject><subject>Female</subject><subject>Gastroenterology and Hepatology</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Hepatitis B e Antigens - blood</subject><subject>Hepatitis B virus - genetics</subject><subject>Hepatitis B, Chronic - diagnosis</subject><subject>Hepatitis B, Chronic - drug therapy</subject><subject>Hepatitis B, Chronic - immunology</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Infectious diseases</subject><subject>Interleukins - blood</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Nucleosides - therapeutic use</subject><subject>Pharmacology. Drug treatments</subject><subject>Pyrimidinones - therapeutic use</subject><subject>Reproducibility of Results</subject><subject>Sensitivity and Specificity</subject><subject>Severity of Illness Index</subject><subject>Thymidine - analogs & derivatives</subject><subject>Treatment Outcome</subject><subject>Viral diseases</subject><subject>Viral hepatitis</subject><issn>0168-8278</issn><issn>1600-0641</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><recordid>eNpFkcFu1DAQhi0EotvCC3BAviBOWWacxPFekNoKupVW4kDvluNMuk6zcbCTRfv2ONoFTiONvvk18w1jHxDWCCi_dOtuT-NaAGJqrEHAK7ZCCZCBLPA1WyVIZUpU6opdx9gBQA6b4i27EgKrHMtixfzWPe95pDAf-OMuE8h7OlIfuWknChwF_030ErlvuRkmd3TB9HzaUzDjiY-BGmcnvr2j2-clxFs_HClE5wfuBm73wQ_O8rSlmdzkIr97x960po_0_lJv2NP3b0_322z34-Hx_naX2VxVU1YVoqnyigpJFmVB9aaslZRQQWHyhkRjqkJiI7FuW9WqulQGa1kSoqrzGvMb9vkcOwb_a6Y46YOLlvreDOTnqDdigwKFEIkUZ9IGH2OgVo_BHUw4aQS9aNadXjTrRfPSS5rT0MdL_FwfqPk38tdrAj5dABOt6dtgBuvif66U6cxyCfp65pJyOjoK2vYuKTP9C50odn4OQ9KkUUehQf9cPro8FBFAlQryP6cQmuw</recordid><startdate>20120401</startdate><enddate>20120401</enddate><creator>Ma, Shi-Wu</creator><creator>Huang, Xuan</creator><creator>Li, Yong-Yin</creator><creator>Tang, Li-Bo</creator><creator>Sun, Xiao-Feng</creator><creator>Jiang, Xiao-Tao</creator><creator>Zhang, Yue-Xin</creator><creator>Sun, Jian</creator><creator>Liu, Zhi-Hua</creator><creator>Abbott, William G.H</creator><creator>Dong, Yu-Hong</creator><creator>Naoumov, Nikolai V</creator><creator>Hou, Jin-Lin</creator><general>Elsevier</general><scope>IQODW</scope><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>7X8</scope></search><sort><creationdate>20120401</creationdate><title>High serum IL-21 levels after 12 weeks of antiviral therapy predict HBeAg seroconversion in chronic hepatitis B</title><author>Ma, Shi-Wu ; Huang, Xuan ; Li, Yong-Yin ; Tang, Li-Bo ; Sun, Xiao-Feng ; Jiang, Xiao-Tao ; Zhang, Yue-Xin ; Sun, Jian ; Liu, Zhi-Hua ; Abbott, William G.H ; Dong, Yu-Hong ; Naoumov, Nikolai V ; Hou, Jin-Lin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c387t-742d737e46ec164eb95b8660704a3de2da7461d61bff8f8b58a1b65e118b3b13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult</topic><topic>Alanine Transaminase - blood</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antiviral agents</topic><topic>Antiviral Agents - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Biomarkers - blood</topic><topic>Disease Progression</topic><topic>DNA, Viral - blood</topic><topic>Female</topic><topic>Gastroenterology and Hepatology</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Hepatitis B e Antigens - blood</topic><topic>Hepatitis B virus - genetics</topic><topic>Hepatitis B, Chronic - diagnosis</topic><topic>Hepatitis B, Chronic - drug therapy</topic><topic>Hepatitis B, Chronic - immunology</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>Infectious diseases</topic><topic>Interleukins - blood</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Nucleosides - therapeutic use</topic><topic>Pharmacology. Drug treatments</topic><topic>Pyrimidinones - therapeutic use</topic><topic>Reproducibility of Results</topic><topic>Sensitivity and Specificity</topic><topic>Severity of Illness Index</topic><topic>Thymidine - analogs & derivatives</topic><topic>Treatment Outcome</topic><topic>Viral diseases</topic><topic>Viral hepatitis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ma, Shi-Wu</creatorcontrib><creatorcontrib>Huang, Xuan</creatorcontrib><creatorcontrib>Li, Yong-Yin</creatorcontrib><creatorcontrib>Tang, Li-Bo</creatorcontrib><creatorcontrib>Sun, Xiao-Feng</creatorcontrib><creatorcontrib>Jiang, Xiao-Tao</creatorcontrib><creatorcontrib>Zhang, Yue-Xin</creatorcontrib><creatorcontrib>Sun, Jian</creatorcontrib><creatorcontrib>Liu, Zhi-Hua</creatorcontrib><creatorcontrib>Abbott, William G.H</creatorcontrib><creatorcontrib>Dong, Yu-Hong</creatorcontrib><creatorcontrib>Naoumov, Nikolai V</creatorcontrib><creatorcontrib>Hou, Jin-Lin</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of hepatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ma, Shi-Wu</au><au>Huang, Xuan</au><au>Li, Yong-Yin</au><au>Tang, Li-Bo</au><au>Sun, Xiao-Feng</au><au>Jiang, Xiao-Tao</au><au>Zhang, Yue-Xin</au><au>Sun, Jian</au><au>Liu, Zhi-Hua</au><au>Abbott, William G.H</au><au>Dong, Yu-Hong</au><au>Naoumov, Nikolai V</au><au>Hou, Jin-Lin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High serum IL-21 levels after 12 weeks of antiviral therapy predict HBeAg seroconversion in chronic hepatitis B</atitle><jtitle>Journal of hepatology</jtitle><addtitle>J Hepatol</addtitle><date>2012-04-01</date><risdate>2012</risdate><volume>56</volume><issue>4</issue><spage>775</spage><epage>781</epage><pages>775-781</pages><issn>0168-8278</issn><eissn>1600-0641</eissn><coden>JOHEEC</coden><abstract>Background & Aims Interleukin-21 (IL-21) stimulates T cell and B cell responses and plays a role in control of chronic viral infections. The role of IL-21 in chronic hepatitis B virus (HBV) infection is not understood. Methods Serum IL-21 levels were measured by enzyme immunoassay in 75 HBeAg-positive chronic hepatitis B (CHB) patients undergoing telbivudine treatment. The findings were validated in 103 patients from a separate clinical trial of telbivudine. A complete response to telbivudine was defined as having both HBeAg seroconversion and serum HBV-DNA level <300 copies/ml by treatment week 52. The proportions of T-cells producing IL-21 and/or expressing programmed death 1 (PD-1) in peripheral blood mononuclear cells were assessed longitudinally during treatment by intracellular cytokine staining and flow cytometry. Results Median serum IL-21 levels at treatment week 12 were significantly higher in patients who did achieve vs. patients who did not achieve a complete response in both the initial (128.4 vs. 69.2 pg/ml, p = 0.003) and the validation (142.2 vs. 89.9 pg/ml, p = 0.004) trials. Serum levels of IL-21 ( p = 0.005) or HBV-DNA ( p = 0.003) levels at treatment week 12 independently predicted HBeAg seroconversion in the first year of treatment. The decrease in PD-1 expression on CD4+ and CD8+ T cells during the first 12 weeks on telbivudine treatment was not correlated with changes in IL-21 concentrations. Conclusions Serum IL-21 levels may be a biomarker for HBeAg seroconversion, and may contribute to individualization of antiviral therapy in HBeAg-positive CHB. IL-21 may also have a role in immunotherapy for CHB.</abstract><cop>Kidlington</cop><pub>Elsevier</pub><pmid>22173154</pmid><doi>10.1016/j.jhep.2011.10.020</doi><tpages>7</tpages></addata></record> |
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| subjects | Adult Alanine Transaminase - blood Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents Antiviral Agents - therapeutic use Biological and medical sciences Biomarkers - blood Disease Progression DNA, Viral - blood Female Gastroenterology and Hepatology Gastroenterology. Liver. Pancreas. Abdomen Hepatitis B e Antigens - blood Hepatitis B virus - genetics Hepatitis B, Chronic - diagnosis Hepatitis B, Chronic - drug therapy Hepatitis B, Chronic - immunology Human viral diseases Humans Infectious diseases Interleukins - blood Male Medical sciences Nucleosides - therapeutic use Pharmacology. Drug treatments Pyrimidinones - therapeutic use Reproducibility of Results Sensitivity and Specificity Severity of Illness Index Thymidine - analogs & derivatives Treatment Outcome Viral diseases Viral hepatitis |
| title | High serum IL-21 levels after 12 weeks of antiviral therapy predict HBeAg seroconversion in chronic hepatitis B |
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