Review
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World J Gastroenterol. May 21, 2013; 19(19): 2864-2882
Published online May 21, 2013. doi: 10.3748/wjg.v19.i19.2864
Herbal hepatotoxicity: Challenges and pitfalls of causality assessment methods
Rolf Teschke, Christian Frenzel, Johannes Schulze, Axel Eickhoff
Rolf Teschke, Axel Eickhoff, Division of Gastroenterology and Hepatology, Department of Internal Medicine II, Klinikum Hanau, D-63450 Hanau, Germany
Rolf Teschke, Axel Eickhoff, Academic Teaching Hospital of the Medical Faculty, Johann Wolfgang Goethe-Universität Frankfurt am Main, D-60590 Frankfurt am Main, Germany
Christian Frenzel, Department of Medicine I, University Medical Center Hamburg Eppendorf, D-20246 Hamburg, Germany
Johannes Schulze, Institute of Industrial, Environmental and Social Medicine, Medical Faculty, Johann Wolfgang Goethe-Universität Frankfurt am Main, D-60590 Frankfurt am Main, Germany
Author contributions: All authors contributed equally to this work.
Correspondence to: Rolf Teschke, MD, Professor of Medicine, Division of Gastroenterology and Hepatology, Department of Internal Medicine II, Klinikum Hanau, Leimenstrasse 20, D-63450 Hanau, Germany. rolf.teschke@gmx.de
Telephone: +49-6181-21859 Fax: +49-6181-2964211
Received: February 21, 2013
Revised: April 11, 2013
Accepted: April 17, 2013
Published online: May 21, 2013
Processing time: 88 Days and 12.5 Hours
Abstract

The diagnosis of herbal hepatotoxicity or herb induced liver injury (HILI) represents a particular clinical and regulatory challenge with major pitfalls for the causality evaluation. At the day HILI is suspected in a patient, physicians should start assessing the quality of the used herbal product, optimizing the clinical data for completeness, and applying the Council for International Organizations of Medical Sciences (CIOMS) scale for initial causality assessment. This scale is structured, quantitative, liver specific, and validated for hepatotoxicity cases. Its items provide individual scores, which together yield causality levels of highly probable, probable, possible, unlikely, and excluded. After completion by additional information including raw data, this scale with all items should be reported to regulatory agencies and manufacturers for further evaluation. The CIOMS scale is preferred as tool for assessing causality in hepatotoxicity cases, compared to numerous other causality assessment methods, which are inferior on various grounds. Among these disputed methods are the Maria and Victorino scale, an insufficiently qualified, shortened version of the CIOMS scale, as well as various liver unspecific methods such as the ad hoc causality approach, the Naranjo scale, the World Health Organization (WHO) method, and the Karch and Lasagna method. An expert panel is required for the Drug Induced Liver Injury Network method, the WHO method, and other approaches based on expert opinion, which provide retrospective analyses with a long delay and thereby prevent a timely assessment of the illness in question by the physician. In conclusion, HILI causality assessment is challenging and is best achieved by the liver specific CIOMS scale, avoiding pitfalls commonly observed with other approaches.

Keywords: Herbal hepatotoxicity; Herb induced liver injury; Herbs; Drug hepatotoxicity; Drug induced liver injury; Causality assessment

Core tip: This review focuses on diagnostic causality assessment algorithms that have been used so far in herb induced liver injury (HILI) cases. Detailed information of the various methods with their strengths and weaknesses is provided including their challenges and pitfalls that emerged during the assessing course. For the physician caring for a patient with suspected HILI, the Council for International Organizations of Medical Sciences (CIOMS) scale is the preferred tool for assessing causality compared to numerous other causality assessment methods, which are inferior on various grounds. CIOMS based assessment should start at the day HILI is suspected to ensure completeness of clinical data.