Liver Injury with Features Mimicking Autoimmune Hepatitis following the Use of Black Cohosh

Abstract

There are a growing number of cases detailing acute hepatic necrosis in patients taking black cohosh (Cimicifuga racemosa), an over-the-counter herbal supplement for management of menopausal symptoms. Our aim is to illustrate two cases of liver injury following the use of black cohosh characterized by histopathological features mimicking autoimmune hepatitis. Both patients reported black cohosh use for at least six months and had no evidence of another cause of liver disease. Their liver biopsies showed a component of centrilobular necrosis consistent with severe drug-induced liver injury. In addition, the biopsies showed characteristics of autoimmune-like liver injury with an interface hepatitis dominated by plasma cells. Although serum markers for autoimmune hepatitis were not particularly elevated, both patients responded to corticosteroids, supporting an immune-mediated component to the liver injury. Liver injury following the use of black cohosh should be included in the list of differential diagnoses for chronic hepatitis with features mimicking autoimmune hepatitis.

Suspected black cohosh hepatotoxicity

“…52,53 Thus, for further cases of black cohosh hepatotoxicity, a diagnostic algorithm as used in our study was proposed. 54 Since the evaluation by the European Medicines Agency and the US Pharmacopeia, 44,45 a growing number of case reports have appeared, [55][56][57][58][59][60][61] which prompted reevaluation of others. 53,[62][63][64][65] The causal relationship in nine cases of suspected hepatotoxicity by the use of black cohosh has been evaluated.…”

Drug-Induced Autoimmune-Like Hepatitis

“…Drugs that have been implicated in less than five reports are benzarone [66], diclofenac [67], fenofibrate [68], meloxicam [69], methylphenidate [70], papaverine [71], pemoline [72], propylthiouracil [73,74], prometrium [27], cephalexin [27], atorvastatin [75][76][77][78], rosuvastatin [79], phenprocoumon [80], terbinafine [81], indometacin [82], imatinib [83], infliximab [84][85][86], and adalimumab [87,88]. Nutritional supplements (hydroxycut) [89], herbal medicines (dai-saiko-to, black cohosh, ma huang, germander) [90][91][92][93][94][95], and an environmental pollutant (trichloroethylene) [96] complement the list of agents that have a weak, uncertain, or rare association with an autoimmunelike hepatitis (Table 1).…”

Black cohosh and suspected hepatotoxicity

“…As a consequence, in their Table 5 of the causality scale, 0 points have been attributed to question 1 as to whether there are previous conclusive reports on this adverse reaction, and the answers were no or do not know. 83 In the latter study, however, there is also some uncertainty regarding causality for BC in their two cases of liver disease. Their first case is declared as duplicate, analyzed already by the USP and refers to a 42-year-old woman with menopausal symptoms.…”

“…83 Concerns that led to this uncertainty included cases in which the timing of liver injury occurred at a relatively short interval after exposure to BC, presence of comorbidities such as cholelithiasis, concomitant use of drugs other than BC that could have potentially triggered the adverse reaction, or the notion that some of the reported cases were indeed examples of autoimmune hepatitis rather than adverse drug reactions. These statements confirm the proposals made by our group 18,19,77 and are in line with the opinion expressed in this review.…”