2011, Number 3
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Ann Hepatol 2011; 10 (3)
Herb induced liver injury presumably caused by black cohosh: A survey of initially purported cases and herbal quality specifications
Teschke R, Schwarzenboeck A, Schmidt-Taenzer W, Wolff A, Hennermann, Karl-Heinz
Language: English
References: 88
Page: 249-259
PDF size: 110.95 Kb.
ABSTRACT
Herb induced liver injury (HILI) is a particular challenge that also applies to purported cases presumably
caused by black cohosh (BC), an herb commonly used to treat menopausal symptoms. We analyzed and reviewed
all published case reports and spontaneous reports of initially alleged BC hepatotoxicity regarding
quality of case details and causality assessments. Shortcomings of data quality were more evident in spontaneous
reports of regulatory agencies compared to published case reports, but assessments with the scale
of CIOMS (Council for the International Organizations of Sciences) or its updated version revealed lack
of causality for BC in all cases. The applied causality methods are structured, quantitative, and liver specific
with clear preference over an
ad hoc causality method or the liver unspecific Naranjo scale. Reviewing
the case data and the reports dealing with quality specifications of herbal BC products, there is general
lack of analysis with respect to authentication of BC in the BC products used by the patients. However, in
one single regulatory study, there was a problem of BC authentication in the analysed BC products, and
other reports addressed the question of impurities and adulterants in a few BC products. It is concluded
that the use of BC may not exert an overt hepatotoxicity risk, but quality problems in a few BC products
were evident that require additional regulatory quality specifications.
REFERENCES
Agarwal VK, McHutchison JG, Hoofnagle JH, Drug-Induced Liver Injury Network (DILIN). Important elements for the diagnosis of drug-induced liver injury. Clin Gastroenterol Hepatol 2010; 8: 463-70.
Rockey DC, Seeff LB, Rochon J, Freston J, Chalasani N, Bonachini M, Fontana RJ, Hayashi PH; for the US Drug-induced Liver Injury Network. Causality assessment in drug-induced liver injury using a structured expert opinion process: Comparison to the Roussel-Uclaf causality assessment method. Hepatology 2010; 51: 2117-26.
Liss G, Lewis JH. Drug-induced liver injury: what was new in 2008? Expert Opin Drug Metab Toxicol 2009; 5: 843-60.
Teschke R. Hepatotoxicity by drugs and dietary supplements: safety perspectives on clinical and regulatory issues. Ann Hepatol 2009; 8: 184-95.
Navarro VJ. Herbal and dietary supplement hepatotoxicity. Semin Liver Dis 2009; 24: 373-82.
Teschke R. Kava hepatotoxicity: pathogenetic aspects and prospective considerations. Liver Int 2010; 30: 1270-9.
Gori L, Firenzuoli F. Is black cohosh a hepatotoxic medicinal herb? Forsch Komplementärmed 2007; 17: 109-10.
Firenzuoli F, Gori L, Roberti di Sarsina P. Black cohosh hepatic safety: follow-up of 107 patients consuming a special Cimicifuga racemosa rhizome herbal extract and review of literature. Evid Based Complement Altern Med 2008. DOI: 10.1093/ecam/nen009.
Borrelli F, Ernst E. Black cohosh (Cimicifuga racemosa): a systematic review of adverse events. Am J Obstet Gynecol 2008; 199: 455-66.
Teschke R, Schwarzenboeck A. Suspected hepatotoxicity by Cimicifuga racemosa rhizoma (black cohosh, root): Critical analysis and structured causality assessment. Phytomedicine 2009; 16: 72-84.
Teschke R, Bahre R, Fuchs J, Wolff A. Black cohosh hepatotoxicity: quantitative causality evaluation in nine suspected cases. Menopause 2009; 16: 956-65.
Teschke R, Schmidt-Taenzer W, Wolff A. Spontaneous reports of assumed herbal hepatotoxicity by black cohosh: Is the liver unspecific Naranjo scale precise enough to ascertain causality? Pharmacoepidemiol Drug Saf 2011. In press. DOI: 10.1002/pds.2127.
Health Canada. Black cohosh products and liver toxicity: update. Canadian Adverse Reaction Newsletter 2010; 20: 1-3. Available from: http://www.hc-sc.gc.ca/dhp-mps/ medeff/bulletin/carn-bcei_v20n1-eng.php#a1t1 [Accessed March 20, 2011].
Col NF, Fairfield KM, Ewan-Whyte C, Miller H. Menopause. Ann Intern Med 2009; 150: ITC4-1-14.
Nelson HD. Menopause. Lancet 2008; 371: 760-70.
Naser B, Schnitker J, Minkin MJ, Garcia de Arriba S, Noltke KU, Osmers R. Suspected black cohosh hepatotoxicity: no evidence by meta-analysis of randomized controlled clinical trials for isopropanolic black cohosh extract. Menopause 2011; 18. In press. DOI: 10.1097/gme.0b013e181fcb2a6.
Teschke R, Bahre R, Genthner A, Fuchs J, Schmidt-Taenzer W, Wolff A. Reply to Letter to the Editor. Suspected black cohosh hepatotoxicity-Causality assessment versus safety signal. Quality versus quantity. Maturitas 2009; 64: 141-2.
Teschke R. Letter to the Editor, in response. Menopause 2010; 17: 1089.
Briese V, Stammwitz U, Friede M, Hennecke von Zepelin HH. Black cohosh-with or without St. John’s wort for symptom-specific climacteric treatment. Results of a large- scale, controlled observational study. Maturitas 2007; 57: 405-14.
Whiting PW, Clouston A, Kerlin P. Black cohosh and other herbal remedies associated with acute hepatitis. Med J Aust 2002; 177: 432-5.
Lontos S, Jones RM, Angus PW, Gow PJ. Acute liver failure associated with the use of herbal preparations containing black cohosh. Med J Aust 2003; 179: 390-1.
Cohen SM, O‘Connor AM, Hart J, Merel N, Te HS. Autoimmune hepatitis associated with the use of black cohosh. Menopause 2004; 11: 575-7.
Levitsky J, Alli TA, Wisecarver J, Sorrell MF. Fulminant liver failure associated with the use of black cohosh. Dig Dis Sci 2005; 50: 538-9.
Lynch CR, Folkers ME, Hutson WR. Fulminant hepatic failure associated with the use of black cohosh: a case report. Liver Transplant 2006; 12: 989-92.
Nisbet BC, O´Connor RE. Black cohosh-induced hepatitis. Del Med J 2007; 79: 441-4.
Dunbar K, Solga SF. Black cohosh, safety, and public awareness. Liver Int 2007; 27: 1017-8.
Joy D, Joy J, Duane P. Black cohosh: a cause of abnormal postmenopausal liver function tests. Climacteric 2008; 11: 84-8.
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: 420-2.
Kerlin P. Herbal hepatitis-black cohosh. Workshop on the safety of black cohosh in clinical studies. In: Proceedings of the NIH. NCCAM Web site. November 22, 2004; 24-6. Available from: http://nccam.nih.gov/news/pastmeetings/ blackcohosh_mtngsumm.pdf#intro [Accessed March 20, 2011]
Thomsen M, Vitetta L, Sali A, Schmidt M. Letter to the Editor: Acute liver failure associated with the use of herbal preparations containing black cohosh. Med J Aust 2004; 180: 598-9.
Cumming FJ, Kelly L. Response to Letter to the Editor. Med J Aust 2004; 180: 599-600.
O‘Connor AM, Merel N, Te HS, Cohen SM. A case of autoimmune hepatitis associated with the use of black cohosh. Am J Gastroenterol 2003; 98(Suppl.): S5165.
Cohen SM. Hepatitis associated with black cohosh: case 1. Workshop on the safety of black cohosh in clinical studies. Proceedings of the NIH. NCCAM Web site. November 22, 2004; 22-4. Available from: http://nccam.nih.gov/news/ pastmeetings/blackcohosh_mtngsumm.pdf#intro [Accessed March 20, 2011].
Nebraska judgement of 8. September 2006. Available from: h t t p : / / a h p a . o r g / p o r t a l s / 0 / p d f s / 06_0908_Blackcohosh_NebraskaDistrictCt.pdf [Accessed March 20, 2011].
Levitsky J, Alli TA, Wisecarver J, Sorrell MF. Fulminant liver failure associated with the use of black cohosh. Dig Dis Sci 2008; 53: 869.
Cohen SM. Hepatitis associated with black cohosh: case 2. Workshop on the safety of black cohosh in clinical studies. Proceedings of the NIH. NCCAM Web site. November 22, 2004; 23-4. Available from: http://nccam.nih.gov/news/ pastmeetings/blackcohosh_mtngsumm.pdf#intro [Accessed March 20, 2011].
Teschke R. Questions regarding causality in presumed black cohosh hepatotoxicity. Del Med J 2008; 80: 233-5.
Nisbet B, O‘Connor R. Response to questions regarding causality in presumed black cohosh hepatotoxicity. Del Med J 2008; 80: 235.
Naser B, Liske E. Letter to the Editor: Liver failure associated with the use of black cohosh for menopausal symptoms. Med J Aust 2009; 190: 99.
Teschke R. Letter to the Editor: Liver failure associated with the use of black cohosh for menopausal symptoms. Med J Aust 2009; 190: 99-100.
Chow ECY, Teo M, Ring JA, Chen JW. Response to Letters to the Editor. Med J Aust 2009; 190: 100.
Teschke R, Bahre R, Genthner A, Fuchs J, Schmidt-Taenzer W, Wolff W. Suspected black cohosh hepatotoxicity - Challenges and pitfalls of causality assessment. Maturitas 2009; 63: 302-14.
Vannacci A, Lapi F, Gallo E, Vietri M, Toti M, Menniti- Ippolito F, et al. A case of hepatitis associated with long-term use of cimicifuga racemosa. Altern Ther 2009; 15: 62-3.
Van de Meerendonk HWPC, Van Hunsel FPAM, Van der Wiel HE. Auto-immunhepatitis door zilverkaars. Bijwerking van een kruidenextract. Ned Tijdschr Geneeskd 2009; 153: 246-9.
Pierard S, Coche CJ, Lanthier P, Dekoninck X, Lanthier N, Rahier J, Geubel AP. Severe hepatitis associated with the use of black cohosh: a report of two cases and an advice for caution. Eur J Gastroenterol Hepatol 2009; 21: 941-5.
Guzman G, Kallwitz ER, Wojewoda C, Chennuri R, Berkes J, Layden TJ, Cotler SJ. Liver injury with features mimicking autoimmune hepatitis following use of black cohosh. Case Rep Med 2009. ID 918156,1-8. DOI: 10.1155/2009/ 918156.
Teschke R. Black cohosh and suspected hepatotoxicity-inconsistencies, confounding variables, and prospective use of a diagnostic causality algorithm: A critical review. Menopause 2010; 17: 426-40.
EMA: Assessment of case reports connected to herbal medicinal products containing cimicifugae racemosae rhizoma (black cohosh, root). Issued May 8, 2007. Available at: h t t p : / / w w w . e m a . e u r o p a . e u / d o c s / e n _ G B / document_library/Herbal_-_HMPC_assessment_report/ 2010/02/WC500074167.pdf [Accessed March 20, 2011].
Mahady GB, Low DT, Barrett ML, Chavez ML, Gardiner P, Ko R, et al. United States Pharmacopeia review of the black cohosh case reports of hepatotoxicity. Menopause 2008; 15: 628-38.
Danan G, Bénichou C. Causality assessment of adverse reactions to drugs-I. A novel method based on the conclusions of international consensus meetings: application to drug-induced liver injuries. J Clin Epidemiol 1993; 46: 1323-30.
Teschke R, Schwarzenboeck A, Hennermann KH. Causality assessment in hepatotoxicity by drugs and dietary supplements. Br J Clin Pharmacol 2008; 66: 758-66.
Maddrey WC. Drug-induced hepatotoxicity. J Clin Gastroenterol 2005; 39(Suppl.): S83-S89.
Teschke R, Bahre R. Severe hepatotoxicity by Indian Ayurvedic herbal products: A structured causality assessment. Ann Hepatol 2009; 8: 258-66.
Batchelor WB, Heathcote J, Wanless IR. Chaparral-induced hepatic injury. Am J Gastroenterol 1995; 90: 831-3.
Perharic-Walton L, Murray V. Toxicity of traditional Chinese herbal remedies. Lancet 1992; 340: 674.
Kane JA, Kane SP, Jain S. Hepatitis induced by traditional Chinese herbs; possible toxic components. Gut 1995; 36: 146-7.
Davies EG, Pollock I, Steel HM. Chinese herbs for eczema. Lancet 1990; 336: 117.
Horowitz RS, Feldhaus K, Dart RC, Stermitz FR, Beck JJ. The clinical spectrum of Jin Bu Huang toxicity. Arch Intern Med 1996; 156: 899-903.
Woolf GM, Petrovic LM, Rojter SE, Wainwright S, Villamil FG, Katkov WN, et al. Acute hepatitis associated with the chinese herbal product Jin Bu Huan. Ann Intern Med 1994; 121: 729-35.
Nadir A, Agrawal S, King PD, Marshall JB. Acute hepatitis associated with the use of a Chinese herbal product, Mahuang. Am J Gastroentol 1996; 91: 1436-8.
Itoh S, Marutani K, Nishijima T, Matsuo S, Itabashi M. Liver injuries induced by herbal medicine, Syo-saiko-to (xiao-chai-hu-tang). Dig Dis Sci 1995; 40: 1845-8.
Larrey D, Vial T, Pauwels A, Castot A, Biour M, David M, Michel H. Hepatitis after Germander (Teucrium chamaedrys) administration: another instance of herbal medicine hepatotoxicity. Ann Intern Med 1992; 117: 129-32.
Laliberté L, Villeneuve JP. Hepatitis after the use of Germander, a herbal remedy. Can Med Assoc J 1996; 154: 1689-92.
Strahl S, Ehret V, Dahm HH, Maier KP. Necrotising hepatitis after taking herbal remedies. Dtsch Med Wschr 1998; 123: 1410-1414 (Article in German).
Benninger J, Schneider HT, Schuppan D, Kirchner T, Hahn EG. Acute hepatitis induced by Greater Celandine (Chelidonium majus). Gastroenterology 1999; 117: 1234-7.
Stickel F, Pöschl G, Seitz HK, Waldherr R, Hahn EG, Schuppan D. Acute hepatitis induced by Greater Celandine (Chelidonium majus). Scand J Gastroenterol 2003; 38: 565-8.
Schoepfer AM, Engel A, Fattinger K, Marbet UA, Criblez D, Reichen J, et al. Herbal does not mean innocuous: ten cases of severe hepatotoxicity associated with dietary supplements from Herbalife® products. J Hepatol 2007; 47: 521-6.
Elinav E, Pinkser G, Safadi R, Pappo O, Bromberg M, Anis E, et al. Association between consumption of Herbalife® nutritional supplements and acute hepatotoxicity. J Hepatol 2007; 47: 514-20.
Colin-Johnes DG, Harvey J. Mistletoe hepatitis. BMJ 1982; 284: 744-5.
Beuers U, Spengler U, Pape GR. Hepatitis after chronic abuse of senna. Lancet 1991; 337: 372-3.
Teschke R, Schwarzenboeck A, Hennermann KH. Kava hepatotoxicity: a clinical survey and critical analysis of 26 suspected cases. Eur J Gastroenterol Hepatol 2008; 20: 1182-93.
Teschke R. Kava hepatotoxicity-a clinical review. Ann Hepatol 2010; 9: 251-65.
Andrade RJ, Lucena MI, Fernández MC, Pelaez G, Pachkoria K, García-Ruiz E, et al; Spanish Group for the Study of Druginduced Liver Disease. Drug-induced liver injury: an analysis of 461 incidences submitted to the Spanish registry over a 10-year period. Gastroenterology 2005; 129: 512-21.
Lucena MI, Camargo R, Andrade RJ, Perez-Sanchez CJ, Sanches de la Cuesta F. Comparison of two clinical scales for causality assessment in hepatotoxicity. Hepatology 2001; 33: 123-30.
Aithal PG, Day CP. The natural history of histologically proved drug induced liver disease. Gut 1999; 44: 731-5.
Bénichou C, Danan G, Flahault A. Causality assessment of adverse reactions to drugs-II. An original model for validation of drug causality assessment methods: case reports with positive rechallenge. J Clin Epidemiol 1993; 46: 1331-6.
Aithal GP, Rawlins MD, Day CP. Accuracy of hepatic adverse drug reaction reporting in one English health region. Br Med J 1999; 319: 154.
Rochon J, Protiva P, Seeff LB, Fontana RJ, Liangpunsakul S, Watkins PB, Davern T, McHutchison JG, for the Drug-Induced Liver Injury Network (DILIN). Reliability of the Roussel Uclaf Causality Assessment Method for assessing causality in drug-induced liver injury. Hepatology 2008; 48: 1175-1183.
O’Shea RS, Dasarathy S, McCullough AJ. Alcoholic liver disease. Am J Gastroenterol 2010; 105: 14-32.
Teschke R, Wolff A. Regulatory causality evaluation methods applied in kava hepatotoxicity: Are they appropriate? Regul Toxicol Pharmacol 2011; 59: 1-7.
Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981; 30: 239-45.
Garcia-Cortéz M, Lucena MI, Pachkoria K, Borraz Y, Hidalgo R, Andrade RJ. Evaluation of naranjo adverse drug reactions probability scale in causality assessment of drug-induced liver injury. Aliment Pharmacol Ther 2008; 27: 780-9.
Sarma DN, Barrett ML, Chavez ML, Gardiner P, Ko R, Mahady GB, et al. Safety of green tea extract: a systematic review by the US Pharmacopeia. Drug Saf 2008; 31: 469-84.
Wang YJ, Dou J, Cross KP, Valerio LG. Computational analysis for hepatic safety signals of constituents present in botanical extracts widely used by women in the United States for treatment of menopausal symptoms. Regul Toxicol Pharmacol 2011; 59: 111-24.
Jiang B, Kronenberg F, Nuntanakorn P, Qiu MH, Kennelly EJ. Evaluation of the botanical authenticity and phytochemical profile of black cohosh products by high-performance liquid chromatography with selected ion monitoring liquid chromatography-mass spectrometry. J Agric Food Chem 2006; 54: 3242-53.
Betz JM, Anderson L, Avigan MI, Barnes J, Farnsworth NR, Gerdén B, et al. Black cohosh. Considerations of safety and benefit. Nutr Today 2009; 44: 155-62.
Sarma ND, Giancaspro GI, Griffiths J, Low Dog T. Black cohosh…more data, please! Menopause 2011; 18. In press. DOI: 10.1097/gme.0b013e3182121eec
Teschke R. Letter to the Editor: United States Pharmacopeia review of the black cohosh case reports of hepatotoxicity. Menopause 2009; 16: 214.