Suspected hepatotoxicity by Cimicifugae racemosae rhizoma (black cohosh, root): critical analysis and structured causality assessment.

Severe hepatotoxicity has been described as spontaneous or case reports in 42 patients in assumed causal relationship with the treatment by Cimicifugae racemosae rhizoma corresponding to the root of black cohosh (BC) for postmenopausal symptoms. However, an assessment by EMEA (European Medicines Agency) has shown a possible or probable causality in only 4 out of 42 patients. A diagnostic algorithm was now applied in the 4 patients with suspected BC hepatotoxicity, which included the qualitative and quantitative causality assessment of the updated system of the Council for International Organizations of Medical Sciences (CIOMS), allowing the study to objectively assess, score and scale the probability in each case. Due to incomplete data, the case of 1 patient was not assessable. In the remaining 3 patients, a severe course of liver disease was apparent, and steroid therapy was initiated under the provisional diagnosis of drug-induced hepatic injury. The analysis shows, however, that the observed liver diseases were unrelated to drugs. Only 1 patient had a favourable course under continued steroid therapy, and the final diagnosis was autoimmune hepatitis. The 2 other patients required liver transplantation under the final diagnosis of herpetic hepatitis established now. Quantitative evaluation showed no causality for BC in all 3 patients regarding the observed severe liver disease. Using a thorough causality assessment in the form of a diagnostic algorithm we have shown that there is no evidence for a causal relationship between treatment by black cohosh and the observed liver disease in the 4 patients.