[Pharmacovigilance and herbal hepatotoxicity: critical aspects and solutions]

Under clinical aspects and in private practice liver diseases are rarely considered in causal connection with the use of herbal drugs and herbal dietary supplements, but in suspected cases a thorough clinical and regulatory causality assessment is mandatory. In initially assumed herbal hepatotoxicity and associated regulatory evaluations by the German regulatory agency, definitions for hepatotoxicity were consistently lacking, upon which causality assssment may have been based. For the description of a risk, even patients were included with lack of established temporal association between herbal use and the appearance the adverse drug reaction (ADR) or with unknown actual liver values, only slightly increased liver values, isolated increased γ-glutamyltransferase, or overt alternative causes including comedication. This continuously led to regulatory high initial case numbers, which were not fundamentally based on clinical and scientific criteria. Heavily debated is also the regulatory use of the WHO method for causality assessment purposes, because this liver unspecific algorithm is neither validated for liver injury nor for any common ADR; this approach therefore is obsolete for a reproducible causality evaluation. Instead, we urgently recommend to use the scale of CIOMS (Council for International Organizations of Medical Sciences), which is liver specific and validated for hepatotoxicity. This is the only way to circumvent future absolute unnecessary and redundant scientific discussions in the regulatory field.