title: Herbal hepatotoxicity and WHO global introspection method.
abstract: Herbal hepatotoxicity is a rare but highly disputed disease because numerous confounding variables may complicate accurate causality assessment. Case evaluation is even more difficult when the WHO global introspection method (WHO method) is applied as diagnostic algorithm. This method lacks liver specificity, hepatotoxicity validation, and quantitative items, basic qualifications required for a sound evaluation of hepatotoxicity cases. Consequently, there are no data available for reliability, sensitivity, specificity, positive and negative predictive value. Its scope is also limited by the fact that it cannot discriminate between a positive and a negative causality attribution, thereby stimulating case overdiagnosing and overreporting. The WHO method ignores uncertainties regarding daily dose, temporal association, start, duration, and end of herbal use, time to onset of the adverse reaction, and course of liver values after herb discontinuation. Insufficiently considered or ignored are comedications, preexisting liver diseases, alternative explanations upon clinical assessment, and exclusion of infections by hepatitis A-C, cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus (HSV), and varicella zoster virus (VZV). We clearly prefer as alternative the scale of CIOMS (Council for International Organizations of Medical Sciences) which is structured, quantitative, liver specific, and validated for hepatotoxicity. In conclusion, causality of herbal hepatotoxicity is best assessed by the liver specific CIOMS scale validated for hepatotoxicity rather than the obsolete WHO method that is liver unspecific and not validated for hepatotoxicity. CIOMS based assessments will ensure the correct diagnosis and exclude alternative diagnosis that may require other specific therapies.
authors.affiliation: Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Academic Teaching Hospital of the Medical Faculty of the Goethe University Frankfurt, Main, Germany. rolf.teschke@gmx.de
authors.forename: Rolf
authors.initials: R
authors.lastname: Teschke
authors.forename: Axel
authors.initials: A
authors.lastname: Eickhoff
authors.forename: Albrecht
authors.initials: A
authors.lastname: Wolff
authors.forename: Christian
authors.initials: C
authors.lastname: Frenzel
authors.forename: Johannes
authors.initials: J
authors.lastname: Schulze
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems; D000465:Algorithms; D015984:Causality; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis* / Q000453:epidemiology; D015986:Confounding Factors, Epidemiologic; D003937:Diagnosis, Differential; D019587:Dietary Supplements / Q000009:adverse effects; D029789:Ephedra / Q000009:adverse effects; D006525:Hepatitis, Viral, Human / Q000175:diagnosis; D006801:Humans; D020901:Kava / Q000009:adverse effects; D031316:Pelargonium / Q000009:adverse effects; D028321:Plant Preparations / Q000009:adverse effects*; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013997:Time Factors; D014944:World Health Organization
chemical_list: C087890:Herbalife; D028321:Plant Preparations