Posts: 22
Threads: 4
Joined: Sep 2013
Yup, I had read that same article, and others, including this one...
In the past three years, four papers or letters have been published purporting to demonstrate a link between the use of black cohosh ingestion and subsequent liver injury. The first publication was from Australia and described six patients with evidence of severe hepatitis linked to taking a range of herbal products.1 Two of these patients were taking black cohosh, although one also was taking other herbs, including skullcap, an herb that can be substituted by Teucrium species, a known hepatotoxic genus.2 The one case attributed to black cohosh alone (case 1) truly was dramatic. Of the cases reported, the most serious illness occurred in a 47-year-old woman taking black cohosh for menopausal symptoms. She required liver transplantation, even though, according to the publication, the patient had been taking the black cohosh for just one week. Histological examination of her liver confirmed severe hepatitis and early fibrosis. The patient did not exhibit eosinophilia and had no signs of any systemic disturbance. Serology for hepatitis A, B and C was negative, but rechallenge with the herb was not performed "for ethical reasons." The dose of black cohosh taken was not specified.
The second publication, also from Australia, described a 52-year-old woman with acute liver failure (case 2).3 She had been taking an herbal formula containing 1:1 liquid extracts prescribed by a pharmacist. Black cohosh 1:1 was 10 percent of the mixture and the daily dose of the combination was 7.5 mL twice a day. The patient underwent successful liver transplantation. Although the authors stated, "Extensive investigation excluded other recognized causes of liver failure," they provided no details of what these investigations were. Analysis was said to confirm the presence of golden seal, black cohosh and ginkgo in the herbal mixture. Other stated ingredients were ground ivy and oats seed.
The third and fourth publications detail single case reports from the U.S. One report described the development of autoimmune hepatitis, which the authors claim was triggered by the use of black cohosh (case 3).4 A 57-year-old diabetic woman presented with a two-week history of lethargy and fatigue. Her medications (all of which had been used for more than two years) included labetalol, fosinopril, verapamil, metformin, aspirin and insulin. Three weeks before presentation, the patient began taking black cohosh tablets (unknown brand or dose) for hot flashes. Drug-induced autoimmune hepatitis, attributed to the black cohosh, was diagnosed. Tests for hepatitis A, B and C were negative.
The most recent case report (case 4) was that of a 50-year-old woman suffering from acute-onset jaundice.5 The provisional diagnosis was autoimmune hepatitis, since tests for hepatitis A, B and C, cytomegalovirus and Epstein-Barr virus all were negative. In the five months prior to the onset of jaundice, the patient was taking black cohosh (500 mg daily) for menopausal symptoms and was not on any other medications.
The case reports linking black cohosh to liver injury have some serious flaws. In particular, for all cases, the presence of black cohosh in the products being consumed was not definitely established. Moreover, in most cases the name of the product and the dosage taken were not specified. Certainly for case 2, there is the assertion that black cohosh was identified in the herbal mixture, but no details of the results or how this was done are provided. The fact that two herbs in the mixture could not be identified makes any argument for the involvement of black cohosh in case 2 fundamentally flawed.
The features of case 1 are baffling. Since the problem developed after one week of taking black cohosh, this would have to be a hypersensitivity reaction if the herb truly was the cause. Yet the patient lacked any features of a hypersensitivity reaction (rash, fever, systemic reaction, eosinophilia). In fact, eosinophilia specifically was stated to be absent. Furthermore, the explant liver showed signs of early fibrosis, a phenomenon that could develop only after months of exposure to the causative agent. Clearly, on the evidence provided, one week of black cohosh is the least likely cause of this patient's liver damage.
For case 3, the authors claimed none of the drugs the patient was taking had been linked to autoimmune hepatitis. Yet a simple search revealed several cases for labetalol in which this drug might have indeed caused an idiosyncratic autoimmune hepatitis, including one overview report of 11 cases from the FDA.14,15,16
In case 4, the authors justify their identification of black cohosh as the cause of the patient's liver injury on the basis of the two flawed Australian publications. In their discussion, they attribute to black cohosh the presence of hepatotoxic alkaloids and salicylates. Such attributions are nonsensical, unsupported by the literature17 and, above all, cast doubt on the credibility and academic diligence of their overall analysis of the case.
Additional problems with the four cases include the lack of positive identification of black cohosh as the cause by either a rechallenge or a lymphocyte stimulation test. While the latter can give false negatives, if positive, it would have provided more conclusive evidence of any link to black cohosh use. But the likelihood is that most of the authors involved never actually saw what the patients were taking (as evidenced by the appalling lack of product and dosage information) and therefore would have been unable to undertake such tests.
The demographics of patients with non-A non-B (idiopathic) hepatitis closely match those of the black cohosh user (female, age 40-50). Hence, the most likely and rational explanation of the cases described is that they are idiopathic hepatitis mistakenly attributed to black cohosh because of the common use of this herb. Once one mistaken case is described in the literature - however poor its quality - others likely will follow in a process akin to a self-fulfilling prophecy. Hopefully, the regulators will not be motivated to act on such poor-quality case reports. The association of black cohosh and DILI remains unproven based on the current evidence.
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