{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T11:55:18Z","timestamp":1790510118791,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2011,3,29]],"date-time":"2011-03-29T00:00:00Z","timestamp":1301356800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2011,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Causality assessment of cases with herbal hepatotoxicity represents a major regulatory challenge and included, in the past, the application of a diagnostic algorithm consisting of causality evaluation methods with either liver\u2010specific or liver\u2010unspecific characteristics. To evaluate various causality assessing methods in cases with suspected herbal hepatotoxicity, two different scales were now used for reasons of comparison.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used the liver\u2010specific scale of the updated Council for International Organizations of Medical Sciences (CIOMS) as well as the Naranjo scale that is not organ specific and therefore not liver specific. Both scales were applied to 22 cases of spontaneous reports with initially assumed herbal hepatotoxicity caused by black cohosh, used for menopausal symptoms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The analysis shows that causality was either unlikely (<jats:italic>n<\/jats:italic>\u2009=\u20096) or excluded (<jats:italic>n<\/jats:italic>\u2009=\u200916), using the updated CIOMS scale. There were various confounding variables: pre\u2010existing liver diseases (<jats:italic>n<\/jats:italic>\u2009=\u20096) including genuine autoimmune hepatitis or alcoholic or cardiac hepatopathy; hepatotoxicity induced by interferon or fluoxetine (<jats:italic>n<\/jats:italic>\u2009=\u20092); marginally increased serum activities of alanine aminotransferase (<jats:italic>n<\/jats:italic>\u2009=\u20092) or gamma\u2010glutamyltranspeptidase (<jats:italic>n<\/jats:italic>\u2009=\u20092) of unassessable causality; a mixed group consisting of unassessable cases (<jats:italic>n<\/jats:italic>\u2009=\u20096) and cases with questionable, poorly documented hepato\u2010biliary diseases (<jats:italic>n<\/jats:italic>\u2009=\u20093); and rosuvastin\u2010induced rhabdomyolysis (<jats:italic>n<\/jats:italic>\u2009=\u20091). These confounding factors were not recognized by the Naranjo scale.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Structured hepatotoxicity\u2010specific causality assessment methods such as the updated CIOMS scale are the preferred tools for causality assessment of assumed herbal hepatotoxicity and should replace the liver\u2010unspecific Naranjo scale. Applying the updated CIOMS scale to cases with initially assumed hepatotoxicity by BC, causality was now found either unlikely or excluded. Copyright \u00a9 2011 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pds.2127","type":"journal-article","created":{"date-parts":[[2011,3,29]],"date-time":"2011-03-29T10:06:28Z","timestamp":1301393188000},"page":"567-582","source":"Crossref","is-referenced-by-count":42,"title":["Spontaneous reports of assumed herbal hepatotoxicity by black cohosh: is the liver\u2010unspecific Naranjo scale precise enough to ascertain causality?"],"prefix":"10.1002","volume":"20","author":[{"given":"Rolf","family":"Teschke","sequence":"first","affiliation":[{"name":"Department of Internal Medicine II, Division of Gastroenterology and Hepatology Klinikum Hanau, Teaching Hospital of the Goethe University Frankfurt\/Main  Hanau Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Schmidt\u2010Taenzer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Division of Gastroenterology and Hepatology Klinikum Hanau, Teaching Hospital of the Goethe University Frankfurt\/Main  Hanau Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albrecht","family":"Wolff","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Division of Gastroenterology and Hepatology Klinikum Hanau, Teaching Hospital of the Goethe University Frankfurt\/Main  Hanau Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,3,29]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1240004"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1240006"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425250903018904"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2010.02308.x"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0895-4356(93)90101-6"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0895-4356(93)90102-7"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1E007"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2008.03655.x"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2008.03264.x"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22442"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.09.011"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2010.02.008"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23577"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gastro.2005.05.006"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21424"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1665-2681(19)31764-8"},{"key":"e_1_2_6_18_1","unstructured":"BfArM (Bundesinstitut f\u00fcr Arzneimittel und Medizinprodukte Bonn. Federal Institute for Drugs and Medicinal Products in Germany). Rejection of drug risks step II. As related to: kava\u2010kava (piper methysticum)\u2010containing and kavain\u2010containing drugs including homeopathic preparations with a final concentration up to and including D4. June 14 2002.http:\/\/www.spc.int\/cis\/documents\/02_0714_BfArM_Kava_Removal.pdf[9 August 2010]."},{"key":"e_1_2_6_19_1","volume-title":"Assessments of Risk of Hepatotoxicity with Kava Products","author":"World Health Organization","year":"2007"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/MEG.0b013e3283036768"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1665-2681(19)31634-5"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-200831060-00003"},{"key":"e_1_2_6_23_1","unstructured":"EMEA. 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