Suspected black cohosh hepatotoxicity--challenges and pitfalls of causality assessment.

OBJECTIVES: Black cohosh (BC) is a herbal drug or herbal dietary supplement used for treatment of menopausal symptoms. Recently, however, reports have appeared about the occurrence of rare toxic liver disease in an assumed relationship with the use of BC.
METHODS: We have analyzed and reviewed the data of all 69 reported cases with suspected BC hepatotoxicity. Causality for BC was assessed utilizing the scale of the original structured quantitative Council for International Organizations of Medical Sciences (CIOMS), or the main-test as its updated form.
RESULTS: With the hepatotoxicity specific causality assessment methods, there was an excluded, unlikely, unrelated or unassessable causality for BC in 68 of 69 cases with liver disease. One patient had a possible causality for BC and a symptomatic cholelithiasis with confounding variables of fatty liver of unknown etiology; unknown BC brand including possible herbal mixture; unknown daily BC dosage; and an unassessable duration of BC usage. In general, the cases of the 69 patients were poorly documented. Confounding variables were: failure to identify the BC product; use of herbal mixtures with multiple ingredients in addition to BC; co-medication with synthetic drugs and dietary supplements including herbal ones; missing temporal association between BC use and development of liver disease; not specified modalities of BC treatment; failure of dechallenge after BC discontinuation; pre-existing liver diseases; insufficiently excluded other liver diseases; presence of alternative liver diseases.
CONCLUSIONS: The analysis of 69 cases shows little, if any, supportive evidence for a significant hepatotoxic risk of BC.