{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:16:06Z","timestamp":1790140566104,"version":"4.0.1"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2019,5,21]],"date-time":"2019-05-21T00:00:00Z","timestamp":1558396800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:p>\n                    <jats:italic toggle=\"yes\">Polygonum multiflorum<\/jats:italic>\n                    (PM) is a well\u2010known Chinese herbal medicine that has been reported to induce inflammation\u2010associated idiosyncratic liver injury. This study aimed to identify the genetic basis of susceptibility to PM\u2010drug\u2010induced liver injury (PM\u2010DILI) and to develop biological markers for predicting the risk of PM\u2010DILI in humans. The major histocompatibility complex (MHC) regions of 11 patients with PM\u2010DILI were sequenced, and all human leukocyte antigen (HLA)\u2013type frequencies were compared to the Han\u2010MHC database. An independent replication study that included 15 patients with PM\u2010DILI, 33 patients with other DILI, and 99 population controls was performed to validate the candidate allele by\n                    <jats:italic toggle=\"yes\">HLA\u2010B<\/jats:italic>\n                    PCR sequence\u2010based typing. A prospective cohort study that included 72 outpatients receiving PM for 4 weeks was designed to determine the influence of the risk allele on PM\u2010DILI. In the pilot study, the frequency of\n                    <jats:italic toggle=\"yes\">HLA\u2010B*35:01<\/jats:italic>\n                    was 45.4% in PM\u2010DILI patients compared with 2.7% in the Han Chinese population (odds ratio [OR], 30.4; 95% confidence interval [CI], 11.7\u201077.8;\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u00a0=\u00a01.9\u00a0\u00d7\u00a010\n                    <jats:sup>\u221210<\/jats:sup>\n                    ). In the independent replication study and combined analyses, a logistic regression model confirmed that\n                    <jats:italic toggle=\"yes\">HLA\u2010B*35:01<\/jats:italic>\n                    is a high\u2010risk allele of PM\u2010DILI (PM\u2010DILI versus other DILI, OR, 86.5; 95% CI, 14.2\u2010527.8,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    = 1.0 \u00d7 10\n                    <jats:sup>\u22126<\/jats:sup>\n                    ; and PM\u2010DILI versus population controls, OR, 143.9; 95% CI, 30.1\u2010687.5,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    = 4.8 \u00d7 10\n                    <jats:sup>\u221210<\/jats:sup>\n                    ). In the prospective cohort study, an asymptomatic increase in transaminase levels was diagnosed in 6 patients, representing a significantly higher incidence (relative risk, 8.0; 95% CI, 1.9\u201033.2;\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u00a0&lt;\u00a00.02) in the\n                    <jats:italic toggle=\"yes\">HLA\u2010B*35:01<\/jats:italic>\n                    carriers (37.5%) than in the noncarriers (4.7%).\n                    <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>\n                    : The\n                    <jats:italic toggle=\"yes\">HLA\u2010B*35:01<\/jats:italic>\n                    allele is a genetic risk factor for PM\u2010DILI and a potential biomarker for predicting PM\u2010DILI in humans.\n                  <\/jats:p>","DOI":"10.1002\/hep.30660","type":"journal-article","created":{"date-parts":[[2019,4,15]],"date-time":"2019-04-15T06:39:27Z","timestamp":1555310367000},"page":"346-357","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":137,"title":["HLA\u2010B*35:01 Allele Is a Potential Biomarker for Predicting Polygonum multiflorum\u2013Induced Liver Injury in Humans"],"prefix":"10.1097","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4316-9140","authenticated-orcid":false,"given":"Chaopeng","family":"Li","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology,Xiangya Hospital, Central South University,Changsha,China"},{"name":"Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology,Central South University,Changsha,China"},{"name":"Engineering Research Center of Applied Technology of Pharmacogenomics,Ministry of Education,Changsha,China"},{"name":"National Clinical Research Center for Geriatric Disorders,Changsha,Hunan,China"},{"name":"Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples,Changsha,Hunan,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tai","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology,Xiangya Hospital, Central South University,Changsha,China"},{"name":"Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology,Central South University,Changsha,China"},{"name":"Engineering Research Center of Applied Technology of Pharmacogenomics,Ministry of Education,Changsha,China"},{"name":"National Clinical Research Center for Geriatric Disorders,Changsha,Hunan,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology,Xiangya Hospital, Central South University,Changsha,China"},{"name":"Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology,Central South University,Changsha,China"},{"name":"Engineering Research Center of Applied Technology of Pharmacogenomics,Ministry of Education,Changsha,China"},{"name":"National Clinical Research Center for Geriatric Disorders,Changsha,Hunan,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengsheng","family":"Zou","sequence":"additional","affiliation":[{"name":"The Fifth Medical Center,General Hospital of PLA,Beijing,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiwu","family":"Wei","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Henan University of Traditional Chinese Medicine,Zhengzhou,Henan,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinfa","family":"Tang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Henan University of Traditional Chinese Medicine,Zhengzhou,Henan,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Xiong","sequence":"additional","affiliation":[{"name":"The Fifth Medical Center,General Hospital of PLA,Beijing,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengyan","family":"Li","sequence":"additional","affiliation":[{"name":"The Fifth Medical Center,General Hospital of PLA,Beijing,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Jing","sequence":"additional","affiliation":[{"name":"The Fifth Medical Center,General Hospital of PLA,Beijing,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"He","sequence":"additional","affiliation":[{"name":"The Fifth Medical Center,General Hospital of PLA,Beijing,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaofang","family":"Bai","sequence":"additional","affiliation":[{"name":"The Fifth Medical Center,General Hospital of PLA,Beijing,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiye","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology,Xiangya Hospital, Central South University,Changsha,China"},{"name":"Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology,Central South University,Changsha,China"},{"name":"Engineering Research Center of Applied Technology of Pharmacogenomics,Ministry of Education,Changsha,China"},{"name":"National Clinical Research Center for Geriatric Disorders,Changsha,Hunan,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhirong","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology,Xiangya Hospital, Central South University,Changsha,China"},{"name":"Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology,Central South University,Changsha,China"},{"name":"Engineering Research Center of Applied Technology of Pharmacogenomics,Ministry of Education,Changsha,China"},{"name":"National Clinical Research Center for Geriatric Disorders,Changsha,Hunan,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Yu","sequence":"additional","affiliation":[{"name":"Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples,Changsha,Hunan,China"},{"name":"School of Pharmaceutical Science,Central South University,Changsha,Hunan,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honghao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology,Xiangya Hospital, Central South University,Changsha,China"},{"name":"Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology,Central South University,Changsha,China"},{"name":"Engineering Research Center of Applied Technology of Pharmacogenomics,Ministry of Education,Changsha,China"},{"name":"National Clinical Research Center for Geriatric Disorders,Changsha,Hunan,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiabo","family":"Wang","sequence":"additional","affiliation":[{"name":"The Fifth Medical Center,General Hospital of PLA,Beijing,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohe","family":"Xiao","sequence":"additional","affiliation":[{"name":"The Fifth Medical Center,General Hospital of PLA,Beijing,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongsheng","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology,Xiangya Hospital, Central South University,Changsha,China"},{"name":"Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology,Central South University,Changsha,China"},{"name":"Engineering Research Center of Applied Technology of Pharmacogenomics,Ministry of Education,Changsha,China"},{"name":"National Clinical Research Center for Geriatric Disorders,Changsha,Hunan,China"},{"name":"Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples,Changsha,Hunan,China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2019,5,21]]},"reference":[{"key":"hep30660-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"W30","DOI":"10.7326\/0003-4819-140-7-200404060-00042-w3","article-title":"New case of acute hepatitis following the consumption of Shou Wu Pian, a Chinese herbal product derived from Polygonum multiflorum","volume":"140","year":"2004","journal-title":"Ann Intern Med"},{"key":"hep30660-bib-0002-20241017","first-page":"459749","article-title":"Liver damage associated with Polygonum multiflorum Thunb.: a systematic review of case reports and case series","volume":"2015","year":"2015","journal-title":"Evid Based Complement Alternat 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multiflorum","volume":"40","year":"2006","journal-title":"J Clin Gastroenterol"},{"key":"hep30660-bib-0006-20241017","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1007\/s11655-017-2543-9","article-title":"Idiosyncratic drug\u2010induced liver injury linked to Polygonum multiflorum: a case study by pharmacognosy","volume":"23","year":"2017","journal-title":"Chin J Integr Med"},{"key":"hep30660-bib-0007-20241017","first-page":"483","article-title":"Metabolomic study on idiosyncratic liver injury induced by different extracts of Polygonum multiflorum in rats integrated with pattern recognition and enriched pathways analysis","volume":"7","year":"2016","journal-title":"Front Pharmacol"},{"key":"hep30660-bib-0008-20241017","doi-asserted-by":"crossref","first-page":"493","DOI":"10.5009\/gnl.2011.5.4.493","article-title":"Drug\u2010induced liver injury: twenty five cases of acute hepatitis following ingestion of Polygonum multiflorum Thunb","volume":"5","year":"2011","journal-title":"Gut Liver"},{"key":"hep30660-bib-0009-20241017","first-page":"1442","article-title":"Clinical analysis of drug\u2010induced liver injury caused by Polygonum multiflorum and its preparations","volume":"35","year":"2015","journal-title":"Chin J Integr Trad West Med"},{"key":"hep30660-bib-0010-20241017","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1007\/s11684-015-0417-8","article-title":"Evidence chain\u2013based causality identification in herb\u2010induced liver injury: exemplification of a well\u2010known liver\u2010restorative herb Polygonum multiflorum","volume":"9","year":"2015","journal-title":"Front Med"},{"key":"hep30660-bib-0011-20241017","first-page":"253","article-title":"Screening for main components associated with the idiosyncratic hepatotoxicity of a tonic herb","volume":"11","year":"2017","journal-title":"Polygonum multiflorum. 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ACG clinical guideline: the diagnosis and management of idiosyncratic drug\u2010induced liver injury","volume":"109","year":"2014","journal-title":"Am J Gastroenterol"},{"key":"hep30660-bib-0017-20241017","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1007\/s11655-018-3000-8","article-title":"Guidelines for the diagnosis and management of herb\u2010induced liver injury","volume":"24","year":"2018","journal-title":"Chin J Integr Med"},{"key":"hep30660-bib-0018-20241017","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1038\/ng.3576","article-title":"Deep sequencing of the MHC region in the Chinese population contributes to studies of complex disease","volume":"48","year":"2016","journal-title":"Nat Genet"},{"key":"hep30660-bib-0019-20241017","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.2307\/2531743","article-title":"Power calculations for matched case\u2010control 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