Genetic variation in STAT4 predicts response to interferon-[alpha] therapy for hepatitis B e antigen-positive chronic hepatitis B
Interferon (IFN)-[alpha] is a first-line therapy for chronic hepatitis B (CHB) patients but only initiates a response in a minority of patients. A genetic variant, rs7574865 in STAT4, was recently reported to be associated with risk of developing CHB and hepatitis B virus-related hepatocellular carc...
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| Veröffentlicht in: | Hepatology (Baltimore, Md.) Md.), 2016-04, Vol.63 (4), p.1102 |
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| container_title | Hepatology (Baltimore, Md.) |
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| creator | Jiang, De-Ke Wu, Xiaopan Qian, Ji Ma, Xiao-Pin Yang, Jingmin Li, Zhuo Wang, Runhua Sun, Li Liu, Fang Zhang, Pengyin Zhu, Xilin Wu, Jia Chen, Kangmei Conran, Carly Zheng, S Lilly Lu, Daru Yu, Long Liu, Ying Xu, Jianfeng |
| description | Interferon (IFN)-[alpha] is a first-line therapy for chronic hepatitis B (CHB) patients but only initiates a response in a minority of patients. A genetic variant, rs7574865 in STAT4, was recently reported to be associated with risk of developing CHB and hepatitis B virus-related hepatocellular carcinoma. We aimed to determine whether this variant is associated with the response to IFN[alpha] treatment for hepatitis B e antigen (HBeAg)-positive CHB patients. We studied 466 HBeAg-positive CHB patients who received either IFN[alpha]-2b (n = 224) or pegylated IFN[alpha]-2a (n = 242) therapy for 48 weeks and were followed for an additional 24 weeks. The rate of sustained virologic response (SVR), defined as HBeAg seroconversion along with hepatitis B virus DNA level |
| doi_str_mv | 10.1002/hep.28423 |
| format | Article |
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A genetic variant, rs7574865 in STAT4, was recently reported to be associated with risk of developing CHB and hepatitis B virus-related hepatocellular carcinoma. We aimed to determine whether this variant is associated with the response to IFN[alpha] treatment for hepatitis B e antigen (HBeAg)-positive CHB patients. We studied 466 HBeAg-positive CHB patients who received either IFN[alpha]-2b (n = 224) or pegylated IFN[alpha]-2a (n = 242) therapy for 48 weeks and were followed for an additional 24 weeks. The rate of sustained virologic response (SVR), defined as HBeAg seroconversion along with hepatitis B virus DNA level <2000 copies/mL at week 72, was compared among patients with different genotypes of rs7574865. After 48 weeks of treatment and 24 weeks off treatment, the SVR rates in the IFN[alpha]-2b and pegylated IFN[alpha]-2a therapy groups were 30.4% and 28.9%, respectively. Compared to the rs7574865 GT/TT genotype, the GG genotype (a risk factor of CHB and hepatitis B virus-related hepatocellular carcinoma) was significantly associated with a reduced SVR rate in both patients who received IFN[alpha]-2b therapy (21.1% versus 37.2%, P = 0.01) and those who received pegylated IFN[alpha]-2a therapy (18.0% versus 41.2%, P = 9.74 × 10-5). In joint analysis of the 466 patients, the GG genotype was associated with an approximately half SVR rate compared to the GT/TT genotype (19.3% versus 39.1%, P = 4.15 × 10-6). A multivariate logistic regression model including rs7574865 and clinical variables showed that rs7574865 was the most significant factor for the prediction of SVR. Conclusion: STAT4 rs7574865 is a reliable predictor of response to IFN[alpha] therapy for HBeAg-positive CHB patients and may be used for optimizing the treatment of CHB. (Hepatology 2016;63:1102-1111)</description><identifier>ISSN: 0270-9139</identifier><identifier>EISSN: 1527-3350</identifier><identifier>DOI: 10.1002/hep.28423</identifier><identifier>CODEN: HPTLD9</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc</publisher><subject>Antigens ; Genotypes ; Health risk assessment ; Hepatitis ; Hepatitis B ; Hepatitis B e antigen ; Hepatocellular carcinoma ; Hepatology ; Interferon ; Liver cancer ; Seroconversion ; Stat4 protein ; α-Interferon</subject><ispartof>Hepatology (Baltimore, Md.), 2016-04, Vol.63 (4), p.1102</ispartof><rights>2016 by the American Association for the Study of Liver Diseases</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids></links><search><creatorcontrib>Jiang, De-Ke</creatorcontrib><creatorcontrib>Wu, Xiaopan</creatorcontrib><creatorcontrib>Qian, Ji</creatorcontrib><creatorcontrib>Ma, Xiao-Pin</creatorcontrib><creatorcontrib>Yang, Jingmin</creatorcontrib><creatorcontrib>Li, Zhuo</creatorcontrib><creatorcontrib>Wang, Runhua</creatorcontrib><creatorcontrib>Sun, Li</creatorcontrib><creatorcontrib>Liu, Fang</creatorcontrib><creatorcontrib>Zhang, Pengyin</creatorcontrib><creatorcontrib>Zhu, Xilin</creatorcontrib><creatorcontrib>Wu, Jia</creatorcontrib><creatorcontrib>Chen, Kangmei</creatorcontrib><creatorcontrib>Conran, Carly</creatorcontrib><creatorcontrib>Zheng, S Lilly</creatorcontrib><creatorcontrib>Lu, Daru</creatorcontrib><creatorcontrib>Yu, Long</creatorcontrib><creatorcontrib>Liu, Ying</creatorcontrib><creatorcontrib>Xu, Jianfeng</creatorcontrib><title>Genetic variation in STAT4 predicts response to interferon-[alpha] therapy for hepatitis B e antigen-positive chronic hepatitis B</title><title>Hepatology (Baltimore, Md.)</title><description>Interferon (IFN)-[alpha] is a first-line therapy for chronic hepatitis B (CHB) patients but only initiates a response in a minority of patients. A genetic variant, rs7574865 in STAT4, was recently reported to be associated with risk of developing CHB and hepatitis B virus-related hepatocellular carcinoma. We aimed to determine whether this variant is associated with the response to IFN[alpha] treatment for hepatitis B e antigen (HBeAg)-positive CHB patients. We studied 466 HBeAg-positive CHB patients who received either IFN[alpha]-2b (n = 224) or pegylated IFN[alpha]-2a (n = 242) therapy for 48 weeks and were followed for an additional 24 weeks. The rate of sustained virologic response (SVR), defined as HBeAg seroconversion along with hepatitis B virus DNA level <2000 copies/mL at week 72, was compared among patients with different genotypes of rs7574865. After 48 weeks of treatment and 24 weeks off treatment, the SVR rates in the IFN[alpha]-2b and pegylated IFN[alpha]-2a therapy groups were 30.4% and 28.9%, respectively. Compared to the rs7574865 GT/TT genotype, the GG genotype (a risk factor of CHB and hepatitis B virus-related hepatocellular carcinoma) was significantly associated with a reduced SVR rate in both patients who received IFN[alpha]-2b therapy (21.1% versus 37.2%, P = 0.01) and those who received pegylated IFN[alpha]-2a therapy (18.0% versus 41.2%, P = 9.74 × 10-5). In joint analysis of the 466 patients, the GG genotype was associated with an approximately half SVR rate compared to the GT/TT genotype (19.3% versus 39.1%, P = 4.15 × 10-6). A multivariate logistic regression model including rs7574865 and clinical variables showed that rs7574865 was the most significant factor for the prediction of SVR. Conclusion: STAT4 rs7574865 is a reliable predictor of response to IFN[alpha] therapy for HBeAg-positive CHB patients and may be used for optimizing the treatment of CHB. (Hepatology 2016;63:1102-1111)</description><subject>Antigens</subject><subject>Genotypes</subject><subject>Health risk assessment</subject><subject>Hepatitis</subject><subject>Hepatitis B</subject><subject>Hepatitis B e antigen</subject><subject>Hepatocellular carcinoma</subject><subject>Hepatology</subject><subject>Interferon</subject><subject>Liver cancer</subject><subject>Seroconversion</subject><subject>Stat4 protein</subject><subject>α-Interferon</subject><issn>0270-9139</issn><issn>1527-3350</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><recordid>eNp9kE1LAzEQhoMoWKsH_0HA89bJJtlsjrVoFQoe3JtIye7OultKEpO04NF_bkAPnjzNMO_HA0PINYMFAyhvR_SLshYlPyEzJktVcC7hlMygVFBoxvU5uYhxBwBalPWMfK3RYpo6ejRhMmlylk6WvjTLRlAfsJ-6FGnA6J2NSJPLasIwYHC2eDV7P5o3mkYMxn_SwQWa-bklTZHeUaTGpukdbeFdzLcj0m7MwUz7Y7skZ4PZR7z6nXPSPNw3q8di87x-Wi03hZeVKFrgUsmWa6Y4r3s5dCiN0V3FBgCjOA6t6vu8VkKUrEbUUnPVVYpXg8acnpObn1of3McBY9ru3CHYTNwyDYqDqJX416WUzC_ToPk3D2ZtZw</recordid><startdate>20160401</startdate><enddate>20160401</enddate><creator>Jiang, De-Ke</creator><creator>Wu, Xiaopan</creator><creator>Qian, Ji</creator><creator>Ma, Xiao-Pin</creator><creator>Yang, Jingmin</creator><creator>Li, Zhuo</creator><creator>Wang, Runhua</creator><creator>Sun, Li</creator><creator>Liu, Fang</creator><creator>Zhang, Pengyin</creator><creator>Zhu, Xilin</creator><creator>Wu, Jia</creator><creator>Chen, Kangmei</creator><creator>Conran, Carly</creator><creator>Zheng, S Lilly</creator><creator>Lu, Daru</creator><creator>Yu, Long</creator><creator>Liu, Ying</creator><creator>Xu, Jianfeng</creator><general>Wiley Subscription Services, Inc</general><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope></search><sort><creationdate>20160401</creationdate><title>Genetic variation in STAT4 predicts response to interferon-[alpha] therapy for hepatitis B e antigen-positive chronic hepatitis B</title><author>Jiang, De-Ke ; Wu, Xiaopan ; Qian, Ji ; Ma, Xiao-Pin ; Yang, Jingmin ; Li, Zhuo ; Wang, Runhua ; Sun, Li ; Liu, Fang ; Zhang, Pengyin ; Zhu, Xilin ; Wu, Jia ; Chen, Kangmei ; Conran, Carly ; Zheng, S Lilly ; Lu, Daru ; Yu, Long ; Liu, Ying ; Xu, Jianfeng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p564-b03575b3917338d5fce5aa9c61f00a73efb7dd00a644218ee95937c6736f9eb03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Antigens</topic><topic>Genotypes</topic><topic>Health risk assessment</topic><topic>Hepatitis</topic><topic>Hepatitis B</topic><topic>Hepatitis B e antigen</topic><topic>Hepatocellular carcinoma</topic><topic>Hepatology</topic><topic>Interferon</topic><topic>Liver cancer</topic><topic>Seroconversion</topic><topic>Stat4 protein</topic><topic>α-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jiang, De-Ke</creatorcontrib><creatorcontrib>Wu, Xiaopan</creatorcontrib><creatorcontrib>Qian, Ji</creatorcontrib><creatorcontrib>Ma, Xiao-Pin</creatorcontrib><creatorcontrib>Yang, Jingmin</creatorcontrib><creatorcontrib>Li, Zhuo</creatorcontrib><creatorcontrib>Wang, Runhua</creatorcontrib><creatorcontrib>Sun, Li</creatorcontrib><creatorcontrib>Liu, Fang</creatorcontrib><creatorcontrib>Zhang, Pengyin</creatorcontrib><creatorcontrib>Zhu, Xilin</creatorcontrib><creatorcontrib>Wu, Jia</creatorcontrib><creatorcontrib>Chen, Kangmei</creatorcontrib><creatorcontrib>Conran, Carly</creatorcontrib><creatorcontrib>Zheng, S Lilly</creatorcontrib><creatorcontrib>Lu, Daru</creatorcontrib><creatorcontrib>Yu, Long</creatorcontrib><creatorcontrib>Liu, Ying</creatorcontrib><creatorcontrib>Xu, Jianfeng</creatorcontrib><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><jtitle>Hepatology (Baltimore, Md.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jiang, De-Ke</au><au>Wu, Xiaopan</au><au>Qian, Ji</au><au>Ma, Xiao-Pin</au><au>Yang, Jingmin</au><au>Li, Zhuo</au><au>Wang, Runhua</au><au>Sun, Li</au><au>Liu, Fang</au><au>Zhang, Pengyin</au><au>Zhu, Xilin</au><au>Wu, Jia</au><au>Chen, Kangmei</au><au>Conran, Carly</au><au>Zheng, S Lilly</au><au>Lu, Daru</au><au>Yu, Long</au><au>Liu, Ying</au><au>Xu, Jianfeng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic variation in STAT4 predicts response to interferon-[alpha] therapy for hepatitis B e antigen-positive chronic hepatitis B</atitle><jtitle>Hepatology (Baltimore, Md.)</jtitle><date>2016-04-01</date><risdate>2016</risdate><volume>63</volume><issue>4</issue><spage>1102</spage><pages>1102-</pages><issn>0270-9139</issn><eissn>1527-3350</eissn><coden>HPTLD9</coden><abstract>Interferon (IFN)-[alpha] is a first-line therapy for chronic hepatitis B (CHB) patients but only initiates a response in a minority of patients. A genetic variant, rs7574865 in STAT4, was recently reported to be associated with risk of developing CHB and hepatitis B virus-related hepatocellular carcinoma. We aimed to determine whether this variant is associated with the response to IFN[alpha] treatment for hepatitis B e antigen (HBeAg)-positive CHB patients. We studied 466 HBeAg-positive CHB patients who received either IFN[alpha]-2b (n = 224) or pegylated IFN[alpha]-2a (n = 242) therapy for 48 weeks and were followed for an additional 24 weeks. The rate of sustained virologic response (SVR), defined as HBeAg seroconversion along with hepatitis B virus DNA level <2000 copies/mL at week 72, was compared among patients with different genotypes of rs7574865. After 48 weeks of treatment and 24 weeks off treatment, the SVR rates in the IFN[alpha]-2b and pegylated IFN[alpha]-2a therapy groups were 30.4% and 28.9%, respectively. Compared to the rs7574865 GT/TT genotype, the GG genotype (a risk factor of CHB and hepatitis B virus-related hepatocellular carcinoma) was significantly associated with a reduced SVR rate in both patients who received IFN[alpha]-2b therapy (21.1% versus 37.2%, P = 0.01) and those who received pegylated IFN[alpha]-2a therapy (18.0% versus 41.2%, P = 9.74 × 10-5). In joint analysis of the 466 patients, the GG genotype was associated with an approximately half SVR rate compared to the GT/TT genotype (19.3% versus 39.1%, P = 4.15 × 10-6). A multivariate logistic regression model including rs7574865 and clinical variables showed that rs7574865 was the most significant factor for the prediction of SVR. Conclusion: STAT4 rs7574865 is a reliable predictor of response to IFN[alpha] therapy for HBeAg-positive CHB patients and may be used for optimizing the treatment of CHB. (Hepatology 2016;63:1102-1111)</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc</pub><doi>10.1002/hep.28423</doi></addata></record> |
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| subjects | Antigens Genotypes Health risk assessment Hepatitis Hepatitis B Hepatitis B e antigen Hepatocellular carcinoma Hepatology Interferon Liver cancer Seroconversion Stat4 protein α-Interferon |
| title | Genetic variation in STAT4 predicts response to interferon-[alpha] therapy for hepatitis B e antigen-positive chronic hepatitis B |
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