Autoimmune hepatitis associated with the use of black cohosh: A case study

University of Chicago, Division of Gastroenterology, Liver Study Unit, Chicago, IL, USA.
Menopause (Impact Factor: 3.36). 09/2004; 11(5):575-7. DOI: 10.1097/01.gme.0000142914.55849.6a
Source: PubMed


Herbal remedies generate more than 1.8 billion dollars in annual sales in the United States. Herbal products have been associated with a wide spectrum of hepatic toxicities. With the recent Women's Health Initiative Study demonstrating increased risk of breast cancer and cardiovascular events associated with hormone therapy, many women may resort to herbal remedies for persistent menopause symptoms. We report a case of autoimmune hepatitis likely triggered by the use of black cohosh (Actaea racemosa), an agent marketed to treat menopause symptoms. Given this case report, we recommend close monitoring of women using this herbal preparation.

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    • "Side effects of black cohosh are rarely reported, however, a few individual cases on possible hepatotoxicity have raised safety issues (Chow et al., 2008; Cohen et al., 2004; Teschke 2009; Teschke et al., 2009). The herb-drug interaction is also of great concern in the safety of black cohosh (Borrelli and Izzo 2009; Kennedy and Seely 2010; Tirona and Bailey 2006). "
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    ABSTRACT: Black cohosh (BC) has been widely applied for the treatment of menopausal symptoms. However, increasing concerns about herb-drug interactions demand the need for studies on the influence of BC on cytochrome 450. Cyp3a11 in liver was induced by 7-fold in wild-type mice treated with 500 mg/kg black cohosh for 28 days compared with the control group as assessed by quantitative real-time PCR; no difference was found in small intestine and kidney, suggesting that up-regulation of Cyp3a11 by black cohosh was liver-specific. Western blot, activity assays, and pharmacokinetic analyses established dose- and time-dependent induction of Cyp3a11. To determine the mechanism of Cyp3a11 induction, including the role of pregnane X receptor (PXR) in vivo and in vitro, respectively, in Pxr-null, PXR-humanized, and double transgenic CYP3A4/hPXR mice, cell-based luciferase assays were employed revealing that mouse PXR played a direct role in the induction of Cyp3a11; human PXR was not activated by black cohosh. Overall, these findings demonstrate that induction of Cyp3a11 is liver-specific and involved only mouse PXR, not the human counterpart. Thus, the incidence of herb-drug interaction in patients administered black cohosh may not be mediated by human PXR and CYP3A4.
    Xenobiotica 10/2010; 41(2):112-23. DOI:10.3109/00498254.2010.527021 · 2.20 Impact Factor
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    • "Black cohosh (Cimicifuga racemosa) is an herbal supplement that is sold over-the-counter for management of menopausal symptoms, menstrual irregularities, and arthritis. There are now a number of manuscripts indicating liver injury from black cohosh [1] [2] [3] [4] [5] [6] [7]. Here, we present two patients who developed a drug-induced liver injury following the use of black cohosh characterized by centrilobular necrosis and histologic features mimicking autoimmune hepatitis (AIH) who improved with corticosteroid therapy. "
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    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.
    Case Reports in Medicine 01/2009; 2009:918156. DOI:10.1155/2009/918156
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    • "In another case report, hepatitis symptoms continued four months after discontinuation of black cohosh, so the hepatitis is unlikely related to the herb (Cohen et al. 2004). Herbs other than black cohosh were being ingested by subjects in some case reports, including ground ivy which contains pugelone, a known liver toxicant (Thomsen et al. 2004). "
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    ABSTRACT: The Women’s Health Initiative found that combination estrogen and progesterone hormone replacement therapy increases breast cancer and cardiovascular disease risk, which compelled many women to seek herbal alternatives such as black cohosh extract (BCE) to relieve their menopausal symptoms. While several clinical trials document the efficacy of BCE in alleviating menopausal symptoms, preclinical studies to determine how BCE works have yielded conflicting results. Part of this is because there is not a universally accepted method to standardize the dose of black cohosh triterpenes, the presumed active ingredients in the extract. Although the mechanism by which BCE relieves symptoms is unknown, several hypotheses have been proposed: it acts 1) as a selective estrogen receptor modulator, 2) through serotonergic pathways, 3) as an antioxidant, or 4) on inflammatory pathways. We found that while the most prominent triterpene in BCE, 23-epi- 26-deoxyactein, suppresses cytokine-induced nitric oxide production in brain microglial cells, the whole BCE extract actually enhanced this pathway. A variety of activities have been reported for black cohosh and its compounds, but the absorption and tissue distribution of these compounds is unknown.
    Integrative Medicine Insights 08/2008; 3(3).
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