title: Causality assessment in hepatotoxicity by drugs and dietary supplements.
abstract: Structured causality assessment of hepatotoxicity by drugs and dietary supplements (DDS) is a major clinical challenge, since temporal associations as the sole criteria for a valid evaluation are not acceptable. Initially, a clear intuition for an ad hoc evaluation is necessary, but only provisional, and must be followed by a diagnostic algorithm using a pretest, main test and post test. The evaluation is based on a variety of items such as latency period, course of alanine aminotransferase and alkaline phosphatase after DDS discontinuation, risk factors, co-medication, previous information on hepatotoxicity of the DDS, response to rechallenge, and exclusion of other diseases. It is essential that practising and hospital physicians as well as other key health professionals, such as pharmacists, gather all information required for a sound causality assessment, obviating major discussions by expert panels, manufacturers and health agencies in face of scanty and fragmentary data. Because pharmacogenetic alterations may trigger metabolic hepatotoxicity by a few DDS, levels in plasma and urine should be measured and may be helpful for diagnosis. Concomitant genotyping of cytochrome P450 and other enzymes may also be useful in future to minimize the risk of unwanted side-effects, including toxic liver disease elicited by DDS.
authors.affiliation: Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Teaching Hospital of the Johann Wolfgang Goethe-University of Frankfurt/Main, Hanau, Germany. rolf_teschke@klinikum-stadt-hanau.de
authors.forename: Rolf
authors.initials: R
authors.lastname: Teschke
authors.forename: Alexander
authors.initials: A
authors.lastname: Schwarzenboeck
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Hennermann
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000209:etiology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003937:Diagnosis, Differential; D019587:Dietary Supplements / Q000009:adverse effects*; D004348:Drug Labeling; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008111:Liver Function Tests; D008297:Male; D028321:Plant Preparations / Q000009:adverse effects*
chemical_list: D015415:Biomarkers; D028321:Plant Preparations; D003577:Cytochrome P-450 Enzyme System