Volume 190 - Issue 2
Liver failure associated with the use of black cohosh for menopausal symptoms
Author: Rolf Teschke
Med J Aust 2009; 190 (2): 99-100. || doi: 10.5694/j.1326-5377.2009.tb02293.x
Published online: 19 January 2009
Published online: 19 January 2009
To the Editor: The case reported by Chow and colleagues of liver failure associated with the use of black cohosh1 requires comment regarding causality. The case has also been the subject of an adverse drug reaction report by the Therapeutic Goods Administration (TGA), and a possible causality has been proposed.2
At presentation on 23 May 2006, the patient was aged 50 years (TGA),2 not 51 as stated by Chow et al.1 Her bodyweight was 88 kg (TGA)2 after gastric bypass for obesity.1 She had been taking black cohosh (20 mg daily) intermittently for 3 years. The subsequent temporal course is essential for assessing causality. According to the TGA report,2 the patient increased the dose of black cohosh to 40 mg daily on 31 March 2006 and stopped taking it on 31 May 2006. The case report describes a 2-month history of lethargy, nausea and arthralgia,1 obviously reported at first presentation. Back calculation shows symptom onset around 23 March 2006. Thus, symptoms emerged 1 week before the dose increase, suggesting a lack of temporal, and hence causal, association.
The patient had several risk factors for severe liver disease.1 Risky use of alcohol for women is defined as more than seven standard drinks per week or more than three drinks on a single occasion.3 The patient had a daily intake of 3–4 units of alcohol, with 1–2 alcohol free days per week (reported by the TGA),2 rendering her at some risk of alcoholic liver disease. Moreover, gastric bypass with partial resection reduces gastric mucosal alcohol dehydrogenase and consequent gastric ethanol metabolism. In combination with rapid gastric passage of alcohol into the jejunum, this leads to high blood ethanol concentrations, another risk factor for liver disease. Risk factors for possible non-alcoholic steatohepatitis and cirrhosis are obesity and gastric bypass.
Other causes were not excluded, including Wilson’s disease (by 24 h urinary copper measurement), hepatitis E, herpetic liver disease and infection by varicella zoster virus, parvovirus B19, parainfluenza virus, adenovirus and cytomegalovirus (by assessing for a change in IgG titre after disappearance of IgM). The marked hepatic mononuclear infiltrate is compatible with some viral infections.
Certainly, various herbal products may cause liver disease. A good example is kava,4 but not black cohosh.5,6 The European Medicines Agency examined 42 cases of liver disease with a suspected association with black cohosh, and found that only four patients had some grades of causality.5 Reassessment showed that two of these patients had herpetic hepatitis, one had autoimmune hepatitis, and the fourth was not assessable.6 Further studies are necessary to show clearly whether black cohosh is potentially hepatotoxic.
References
- Chow ECY, Teo M, Ring JA, Chen JW. Liver failure associated with the use of black cohosh for menopausal symptoms. Med J Aust 2008; 188: 420-422. 0_CBBHEICJ
- Australian Government Department of Health and Ageing Therapeutic Goods Administration. Public case detail for case number 220336, recorded as reported to the Adverse Drug Reactions Unit, 25 July 2006. 0_CBBDECDG
- Saitz R. Clinical practice. Unhealthy alcohol use. N Engl J Med 2005; 352: 596-607. 0_i1091871
- Teschke R, Schwarzenboeck A, Hennermann KH. Kava hepatotoxicity: a clinical survey and critical analysis of 26 suspected cases. Eur J Gastroenterol Hepatol 2008; 20:1182-1193. 0_i1091873
- European Medicines Agency, Committee on Herbal Medicinal Products (HMPC). Assessment of case reports connected to herbal medicinal products containing Cimicifugae racemosae rhizoma (black cohosh, root). London: EMEA, 2007. http://www.emea.europa.eu/pdfs/human/hmpc/26925806en.pdf (accessed Jul 2008).
- Teschke R, Schwarzenboeck A. Suspected hepatotoxicity by Cimicifugae racemosae rhizoma (black cohosh, root): critical analysis and structured causality assessment. Phytomedicine 2008; doi 10.1016/j.phymed.2080.09.009. 0_i1091877