title: Kava hepatotoxicity: regulatory data selection and causality assessment.
abstract: BACKGROUND
  Kava hepatotoxicity in 20 patients from Germany has been debated worldwide following a regulatory ad hoc causality assessment and ban of kava, an anxiolytic herbal remedy obtained from the rhizome of Piper methysticum Forster.
  
  
  OBJECTIVE
  We assessed causality with a quantitative structured causality analysis in all 20 cases of patients with liver disease, presented by the German regulatory agency that assumed a causal relationship with the use of kava extracts.
  
  
  METHODS
  The quantitative scale of CIOMS (Council for International Organizations of Medical Sciences) in its updated form was employed for causality assessment and quality evaluation of the regulatory data presentation.
  
  
  RESULTS
  The regulatory information is scattered and selective, and items essential for causality assessment, such as exclusion of kava independent causes, were not, or only marginally, considered by the regulator. Quantitative causality assessment for kava was possible (n=2), unlikely (n=12), or excluded (n=6), showing no concordance with the regulatory ad hoc causality evaluation.
  
  
  CONCLUSIONS
  The regulatory data regarding kava hepatotoxicity is selective and of low quality, not supportive of the regulatory proposed causality; but instead, is an explanation of the overall causality discussions of kava hepatotoxicity. We are proposing that the regulatory agency reports data in full length and reevaluates causality.
authors.affiliation: Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Teaching Hospital of the Johann Wolfgang Goethe-University, Frankfurt/Main, Hanau, Germany. rolf_teschke@klinikum-hanau.de
authors.forename: R
authors.initials: R
authors.lastname: Teschke
authors.forename: A
authors.initials: A
authors.lastname: Wolff
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015984:Causality; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D020901:Kava / Q000633:toxicity*; D008297:Male; D008875:Middle Aged; D010936:Plant Extracts / Q000633:toxicity*
chemical_list: D010936:Plant Extracts