Semin Liver Dis 2014; 34(02): 172-193
DOI: 10.1055/s-0034-1375958
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Hepatotoxicity Induced by Herbal and Dietary Supplements

Victor J. Navarro
1   Division of Hepatology, Einstein Medical Center, Philadelphia, Pennsylvania
,
M. Isabel Lucena
2   Clinical Pharmacology Service, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Malaga University, Malaga, Spain
› Author Affiliations
Further Information

Publication History

Publication Date:
31 May 2014 (online)

Abstract

Herbals and dietary supplements (HDS) can cause hepatotoxicity. Regulation of HDS varies across the globe. In the United States, it is defined by a law that is now two decades old. More recent regulatory approaches in Europe still do not require testing for premarket safety. The true incidence of hepatotoxicity from HDS is unknown. The presentation is most often with a hepatocellular enzyme pattern, and the outcomes can be severe, leading to transplantation in some circumstances. The diagnosis of hepatotoxicity due to HDS is made in the same way as for drugs. However, patients often must be coaxed into revealing a history of use. No causality assessment approach is perfectly suited for hepatotoxicity from HDS, but the Roussel Uclaf Causality Assessment Method is most used. Future endeavors must focus on defining epidemiology, establishing an accepted nomenclature, and identifying culprit ingredients, predisposing host factors, and useful biomarkers for injury.

 
  • References

  • 1 Navarro VJ. Herbal and dietary supplement hepatotoxicity. Semin Liver Dis 2009; 29 (4) 373-382
  • 2 Commission on Dietary Supplement Labels. Chapter I Dietary Supplement Health And Education Act of 1994. Available at: http://www.health.gov/dietsupp/ch1.htm . Accessed January 13, 2014
  • 3 Hatch Leads Efforts to Prevent Overregulation of Dietary Supplements. Available at: http://www.hatch.senate.gov/public/index.cfm/2012/5/hatch-leads-efforts-to-prevent-overregulation-of-dietary-supplements . Accessed January 13, 2014
  • 4 US Food and Drug Administration. Uprizing 2.0: Recall - Undeclared Drug Ingredient: Synthetic Steroid. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm274746.htm . Accessed January 13, 2014
  • 5 US Food and Drug Administration. OxyElite Pro Supplements Recalled. Available at: http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm374742.htm . Accessed January 14, 2014
  • 6 US Food and Drug Administration. Medical Foods Guidance Documents & Regulatory Information. Available at: http://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/MedicalFoods/default.htm . Accessed April 9, 2014
  • 7 Chalasani N, Vuppalanchi R, Navarro V , et al. Acute liver injury due to flavocoxid (Limbrel), a medical food for osteoarthritis: a case series. Ann Intern Med 2012; 156 (12) 857-860 , W297-300
  • 8 European Commission. Herbal Medicinal Products. Available at: http://ec.europa.eu/health/human-use/herbal-medicines/index_en.htm . Accessed January 14, 2014
  • 9 European Medicines Agency. Committee on Herbal Medicinal Products (HMPC). Available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/about_us/general/general_content_000264.jsp . Accessed January 13, 2014
  • 10 European Medicines Agency. Herbal Medicines for Human Use. Available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/landing/herbal_medicines_search_landing_page.jsp&mid= . Accessed January 13, 2014
  • 11 Medicines and Healthcare Products Regulatory Agency (MRHA). Herbal Medicines Advisory Committee. Available at: http://www.mhra.gov.uk/Committees/Medicinesadvisorybodies/HerbalMedicinesAdvisoryCommittee/index.htm . Accessed January 13, 2014
  • 12 The WHO Essential Medicines and Health Products Information Portal. Available at: http://apps.who.int/medicinedocs/en . Accessed January 13, 2014
  • 13 World Health Organization. International Regulatory Cooperation for Herbal Medicines (IRCH). Available at: http://www.who.int/medicines/areas/traditional/irch/en/ . Accessed January 13, 2014
  • 14 World Health Organization. General Information on IRCH. Available at: http://www.who.int/medicines/areas/traditional/geninfo/en/ . Accessed January 13, 2014
  • 15 Eisenberg DM, Kessler RC, Foster C, Norlock FE, Calkins DR, Delbanco TL. Unconventional medicine in the United States. Prevalence, costs, and patterns of use. N Engl J Med 1993; 328 (4) 246-252
  • 16 Bailey RL, Gahche JJ, Lentino CV , et al. Dietary supplement use in the United States, 2003-2006. J Nutr 2011; 141 (2) 261-266
  • 17 Picciano MF, Dwyer JT, Radimer KL , et al. Dietary supplement use among infants, children, and adolescents in the United States, 1999-2002. Arch Pediatr Adolesc Med 2007; 161 (10) 978-985
  • 18 Bailey RL, Gahche JJ, Miller PE, Thomas PR, Dwyer JT. Why US adults use dietary supplements. JAMA Intern Med 2013; 173 (5) 355-361
  • 19 World Health Organization. WHO traditional medicine strategy 2002–2005. Geneva: WHO; 2002
  • 20 Skeie G, Braaten T, Hjartåker A , et al. Use of dietary supplements in the European Prospective Investigation into Cancer and Nutrition calibration study. Eur J Clin Nutr 2009; 63 (Suppl. 04) S226-S238
  • 21 Lindstrom A, Ooyen C, Lynch ME, Blumenthal M. Herb supplement sales increase 5.5% in 2012: herbal supplement sales rise for 9th consecutive year. Herbal Gram 2013; 99: 60-65
  • 22 PRWeb Focus. Global Herbal Supplements and Remedies Market to Reach US$107 Billion by 2017, According to New Report by Global Industry Analysts, Inc. Available at: http://www.prweb.com/releases/herbal_supplements/herbal_remedies/prweb9260421.htm . Accessed January 13, 2014
  • 23 Björnsson ES, Bergmann OM, Björnsson HK, Kvaran RB, Olafsson S. Incidence, presentation, and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology 2013; 144 (7) 1419-1425 , e1–e3, quiz e19–e20
  • 24 Chalasani N, Fontana RJ, Bonkovsky HL , et al; Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology 2008; 135 (6) 1924-1934 , e1–e4
  • 25 Medina-Cáliz I, González-Jiménez A, Bessone F , et al. Variations in drug-induced liver injury (DILI) between different prospective DILI registries. Clin Ther 2013; 35 (8 Suppl): S24
  • 26 Bessone F, Hernandez N, Sanchez A , et al. The Spanish–Latin American DILI Network: preliminary results from a collaborative strategic initiative. J Hepatol 2013; 58 (Suppl. 01) 212-213
  • 27 Suk KT, Kim DJ, Kim CH , et al. A prospective nationwide study of drug-induced liver injury in Korea. Am J Gastroenterol 2012; 107 (9) 1380-1387
  • 28 Wai CT, Tan BH, Chan CL , et al. Drug-induced liver injury at an Asian center: a prospective study. Liver Int 2007; 27 (4) 465-474
  • 29 Wang YP, Shi B, Chen YX, Xu J, Jiang CF, Xie WF. Drug-induced liver disease: an 8-year study of patients from one gastroenterological department. J Dig Dis 2009; 10 (3) 195-200
  • 30 Devarbhavi H, Dierkhising R, Kremers WK, Sandeep MS, Karanth D, Adarsh CK. Single-center experience with drug-induced liver injury from India: causes, outcome, prognosis, and predictors of mortality. Am J Gastroenterol 2010; 105 (11) 2396-2404
  • 31 Navarro VJ, Barnhart HX, Bonkovsky HL , et al. The rising burden of herbal and dietary supplement induced hepatotoxicity in the U.S.A. Abstract presented at: 64th Annual Meeting of the American Association for the Study of Liver Diseases. ; November 1–5, 2013 ; Washington, DC
  • 32 Reuben A, Koch DG, Lee WM ; Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology 2010; 52 (6) 2065-2076
  • 33 Wu CH, Wang CC, Kennedy J. Changes in herb and dietary supplement use in the U.S. adult population: a comparison of the 2002 and 2007 National Health Interview Surveys. Clin Ther 2011; 33 (11) 1749-1758
  • 34 Andrade RJ, Lucena MI, Fernández MC , et al; Spanish Group for the Study of Drug-Induced Liver Disease. Drug-induced liver injury: an analysis of 461 incidences submitted to the Spanish registry over a 10-year period. Gastroenterology 2005; 129 (2) 512-521
  • 35 Björnsson E, Olsson R. Outcome and prognostic markers in severe drug-induced liver disease. Hepatology 2005; 42 (2) 481-489
  • 36 Russo MW, Galanko JA, Shrestha R, Fried MW, Watkins P. Liver transplantation for acute liver failure from drug induced liver injury in the United States. Liver Transpl 2004; 10 (8) 1018-1023
  • 37 Estes JD, Stolpman D, Olyaei A , et al. High prevalence of potentially hepatotoxic herbal supplement use in patients with fulminant hepatic failure. Arch Surg 2003; 138 (8) 852-858
  • 38 Fernández-Castañer A, García-Cortés M, Lucena MI , et al. [An analysis of the causes, characteristics, and consequences of reexposure to a drug or compound responsible for a hepatotoxicity event]. Rev Esp Enferm Dig 2008; 100 (5) 278-284
  • 39 Blendon RJ, DesRoches CM, Benson JM, Brodie M, Altman DE. Americans' views on the use and regulation of dietary supplements. Arch Intern Med 2001; 161 (6) 805-810
  • 40 Robinson A, McGrail MR. Disclosure of CAM use to medical practitioners: a review of qualitative and quantitative studies. Complement Ther Med 2004; 12 (2-3) 90-98
  • 41 Eisenberg DM, Davis RB, Ettner SL , et al. Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey. JAMA 1998; 280 (18) 1569-1575
  • 42 LiverTox® Clinical and Research Information on Drug Induced Liver Injury. Available at: http://livertox.nih.gov/ . Accessed January 13, 2014
  • 43 lsharkawy AM, McPherson S, Masson S , et al. Cholestasis secondary to anabolic steroid use in young men. BMJ 2012; 344: 468
  • 44 Turani H, Levi J, Zevin D, Kessler E. Hepatic lesions in patients on anabolic androgenic therapy. Isr J Med Sci 1983; 19 (4) 332-337
  • 45 Timcheh-Hariri A, Balali-Mood M, Aryan E, Sadeghi M, Riahi-Zanjani B. Toxic hepatitis in a group of 20 male body-builders taking dietary supplements. Food Chem Toxicol 2012; 50 (10) 3826-3832
  • 46 Singh V, Rudraraju M, Carey EJ , et al. Severe hepatotoxicity caused by a methasteron-containing performance-enhancing supplement. J Clin Gastroenterol 2009; 43 (3) 287
  • 47 Tandon BN, Tandon HD, Tandon RK, Narndranathan M, Joshi YK. An epidemic of veno-occlusive disease of liver in central India. Lancet 1976; 2 (7980) 271-272
  • 48 Weston CFM, Cooper BT, Davies JD, Levine DF. Veno-occlusive disease of the liver secondary to ingestion of comfrey. Br Med J (Clin Res Ed) 1987; 295 (6591) 183
  • 49 Bras G, Jelliffe DB, Stuart KL. Veno-occlusive disease of liver with nonportal type of cirrhosis, occurring in Jamaica. AMA Arch Pathol 1954; 57 (4) 285-300
  • 50 Stillman AS, Huxtable R, Consroe P, Kohnen P, Smith S. Hepatic veno-occlusive disease due to pyrrolizidine (Senecio) poisoning in Arizona. Gastroenterology 1977; 73 (2) 349-352
  • 51 US Food and Drug Administration. Federal Food, Drug, and Cosmetic Act (FD&C Act). Available at: http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/default.htm. Accessed January 13, 2014
  • 52 Kneifel W, Czech E, Kopp B. Microbial contamination of medicinal plants—a review. Planta Med 2002; 68 (1) 5-15
  • 53 Stickel F, Droz S, Patsenker E , et al. Severe hepatotoxicity following ingestion of Herbalife contaminated with Bacillus subtilis. J Hepatol 2009; 50: 111-117
  • 54 Saper RB, Phillips RS, Sehgal A , et al. Lead, mercury, and arsenic in US- and Indian-manufactured Ayurvedic medicines sold via the Internet. JAMA 2008; 300 (8) 915-923
  • 55 Wong MK, Tan P, Wee YC. Heavy metals in some Chinese herbal plants. Biol Trace Elem Res 1993; 36 (2) 135-142
  • 56 Ernst E. Heavy metals in traditional Indian remedies. Eur J Clin Pharmacol 2002; 57 (12) 891-896
  • 57 Miller GM, Stripp R. A study of western pharmaceuticals contained within samples of Chinese herbal/patent medicines collected from New York City's Chinatown. Leg Med (Tokyo) 2007; 9 (5) 258-264
  • 58 Fleshner N, Harvey M, Adomat H , et al. Evidence for contamination of herbal erectile dysfunction products with phosphodiesterase type 5 inhibitors. J Urol 2005; 174 (2) 636-641 , discussion 641, quiz 801
  • 59 Komes D, Belščak-Cvitanović A, Horžić D, Rusak G, Likić S, Berendika M. Phenolic composition and antioxidant properties of some traditionally used medicinal plants affected by the extraction time and hydrolysis. Phytochem Anal 2011; 22 (2) 172-180
  • 60 Harkey MR, Henderson GL, Gershwin ME, Stern JS, Hackman RM. Variability in commercial ginseng products: an analysis of 25 preparations. Am J Clin Nutr 2001; 73 (6) 1101-1106
  • 61 Ye F, Wang H, Jiang S , et al. Quality evaluation of commercial extracts of Scutellaria baicalensis. Nutr Cancer 2004; 49 (2) 217-222
  • 62 Navarro VJ, Bonkovsky HL, Hwang SI, Vega M, Barnhart H, Serrano J. Catechins in dietary supplements and hepatotoxicity. Dig Dis Sci 2013; 58 (9) 2682-2690
  • 63 Newmaster SG, Grguric M, Shanmughanandhan D, Ramalingam S, Ragupathy S. DINA barcoding detects contamination and substitution in North American herbal products. BMC Med 2013; 11: 2-13
  • 64 Danan G, Benichou 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 (11) 1323-1330
  • 65 Benichou 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 (11) 1331-1336
  • 66 Maria VAJ, Victorino RMM. Development and validation of a clinical scale for the diagnosis of drug-induced hepatitis. Hepatology 1997; 26 (3) 664-669
  • 67 Aithal GP, Rawlins MD, Day CP. Clinical diagnostic scale: a useful tool in the evaluation of suspected hepatotoxic adverse drug reactions. J Hepatol 2000; 33 (6) 949-952
  • 68 Naranjo CA, Busto U, Sellers EM , et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981; 30 (2) 239-245
  • 69 Sarma DN, Barrett ML, Chavez ML , et al. Safety of green tea extracts : a systematic review by the US Pharmacopeia. Drug Saf 2008; 31 (6) 469-484
  • 70 Bénichou C. Criteria of drug-induced liver disorders. Report of an international consensus meeting. J Hepatol 1990; 11 (2) 272-276
  • 71 Lucena MI, Camargo R, Andrade RJ, Pérez-Sanchez CJ, Sánchez De La Cuesta F. Comparison of two clinical scales for causality assessment in hepatotoxicity. Hepatology 2001; 33 (1) 123-130
  • 72 Fontana RJ, Watkins PB, Bonkovsky HL , et al. Rationale, design and conduct of the Drug Induced Liver Injury Network prospective study. Drug Saf 2009; 32: 55-68
  • 73 Navarro VJ, Barnhart HX, Bonkovsky HL , et al. Diagnosing hepatotoxicity attributable to herbal and dietary supplements: test-retest reliability of novel causality assessment tool. J Hepatol 2012; 55 (Suppl. 02) S536
  • 74 Teschke R, Schwarzenboeck A, Eickhoff A, Frenzel C, Wolff A, Schulze J. Clinical and causality assessment in herbal hepatotoxicity. Expert Opin Drug Saf 2013; 12 (3) 339-366
  • 75 Stickel F, Kessebohm K, Weimann R, Seitz HK. Review of liver injury associated with dietary supplements. Liver Int 2011; 31 (5) 595-605
  • 76 Strader DB, Navarro VJ, Seeff LB. Hepatotoxicity of herbal preparations. In: Boyer TD, Manns MP, Sanyal AJ, , eds. Zakim and Boyer's Hepatology: A Textbook of Liver Disease. 6th ed. Philadelphia, PA: Saunders; 2012: 462-475
  • 77 Bunchorntavakul C, Reddy KR. Review article: herbal and dietary supplement hepatotoxicity. Aliment Pharmacol Ther 2013; 37 (1) 3-17
  • 78 Ishak KG. Hepatic lesions caused by anabolic and contraceptive steroids. Semin Liver Dis 1981; 1 (2) 116-128
  • 79 Haupt HA, Rovere GD. Anabolic steroids: a review of the literature. Am J Sports Med 1984; 12 (6) 469-484
  • 80 DesJardins M. Supplement use in the adolescent athlete. Curr Sports Med Rep 2002; 1 (6) 369-373
  • 81 Martin DJ, Partridge BJ, Shields W. Hepatotoxicity associated with the dietary supplement N.O.-XPLODE. Ann Intern Med 2013; 159 (7) 503-504
  • 82 Vitetta l, Thomsen M, Sali A. Black cohosh and other herbal remedies associated with acute hepatitis. Med J Aust 2003; 21: 411-412
  • 83 Nisbet BC, O'Connor RE. Black cohosh-induced hepatitis. Del Med J 2007; 79 (11) 441-444
  • 84 Whiting PW, Clouston A, Kerlin P. Black cohosh and other herbal remedies associated with acute hepatitis. Med J Aust 2002; 177 (8) 440-443
  • 85 Vannacci A, Lapi F, Gallo E , et al. A case of hepatitis associated with long-term use of Cimicifuga racemosa. Altern Ther Health Med 2009; 15 (3) 62-63
  • 86 Pierard S, Coche JC, Lanthier P , et al. 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 (8) 941-945
  • 87 Cohen SM, O'Connor AM, Hart J, Merel NH, Te HS. Autoimmune hepatitis associated with the use of black cohosh: a case study. Menopause 2004; 11 (5) 575-577
  • 88 Mahady GB, Low Dog T, Barrett ML , et al. United States pharmacopeia review of the black cohosh case reports of hepatotoxicity. Menopause 2008; 15: 628-638
  • 89 Verbitski SM, Gourdin GT, Ikenouye LM, McChesney JD, Hildreth J. Detection of Actaea racemosa adulteration by thin-layer chromatography and combined thin-layer chromatography-bioluminescence. J AOAC Int 2008; 91 (2) 268-275
  • 90 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 (7) 390-391
  • 91 Levitsky J, Alli TA, Wisecarver J, Sorrell MF. Fulminant liver failure associated with the use of black cohosh. Dig Dis Sci 2005; 50 (3) 538-539
  • 92 Lynch CR, Folkers ME, Hutson WR. Fulminant hepatic failure associated with the use of black cohosh: a case report. Liver Transpl 2006; 12 (6) 989-992
  • 93 Sheikh NM, Philen RM, Love LA. Chaparral-associated hepatotoxicity. Arch Intern Med 1997; 157 (8) 913-919
  • 94 Lambert JD, Kennett MJ, Sang S, Reuhl KR, Ju J, Yang CS. Hepatotoxicity of high oral dose (-)-epigallocatechin-3-gallate in mice. Food Chem Toxicol 2010; 48 (1) 409-416
  • 95 García-Cortés M, Borraz Y, Lucena MI , et al. [Liver injury induced by “natural remedies”: an analysis of cases submitted to the Spanish Liver Toxicity Registry]. Rev Esp Enferm Dig 2008; 100 (11) 688-695
  • 96 Bonkovsky HL. Hepatotoxicity associated with supplements containing Chinese green tea (Camellia sinensis). Ann Intern Med 2006; 144 (1) 68-71
  • 97 Skoulidis F, Alexander GJM, Davies SE. Ma huang associated acute liver failure requiring liver transplantation. Eur J Gastroenterol Hepatol 2005; 17 (5) 581-584
  • 98 Neff GW, Reddy KR, Durazo FA, Meyer D, Marrero R, Kaplowitz N. Severe hepatotoxicity associated with the use of weight loss diet supplements containing ma huang or usnic acid. J Hepatol 2004; 41 (6) 1062-1064
  • 99 Nadir A, Agrawal S, King PD, Marshall JB. Acute hepatitis associated with the use of a Chinese herbal product, ma-huang. Am J Gastroenterol 1996; 91 (7) 1436-1438
  • 100 MacGregor FB, Abernethy VE, Dahabra S, Cobden I, Hayes PC. Hepatotoxicity of herbal remedies. BMJ 1989; 299 (6708) 1156-1157
  • 101 Elinav E, Pinsker G, Safadi R , et al. Association between consumption of Herbalife nutritional supplements and acute hepatotoxicity. J Hepatol 2007; 47 (4) 514-520
  • 102 Schoepfer AM, Engel A, Fattinger K , et al. Herbal does not mean innocuous: ten cases of severe hepatotoxicity associated with dietary supplements from Herbalife products. J Hepatol 2007; 47 (4) 521-526
  • 103 Manso G, López-Rivas L, Salgueiro ME , et al. Continuous reporting of new cases in Spain supports the relationship between Herbalife® products and liver injury. Pharmacoepidemiol Drug Saf 2011; 20 (10) 1080-1087
  • 104 Halegoua-De Marzio D, Vega M, Schifter-Weber J , et al. An International Effort to Assess Hepatotoxicity Associated with Some Herbalife® Products. Hepatology 2013; 58 (Suppl. 01) 383
  • 105 Dara L, Hewett J, Lim JK. Hydroxycut hepatotoxicity: a case series and review of liver toxicity from herbal weight loss supplements. World J Gastroenterol 2008; 14 (45) 6999-7004
  • 106 Fong TL, Klontz KC, Canas-Coto A , et al. Hepatotoxicity due to hydroxycut: a case series. Am J Gastroenterol 2010; 105 (7) 1561-1566
  • 107 Strahl S, Ehret V, Dahm HH, Maier KP. [Necrotizing hepatitis after taking herbal remedies]. Dtsch Med Wochenschr 1998; 123 (47) 1410-1414
  • 108 Escher M, Desmeules J, Giostra E, Mentha G. Hepatitis associated with Kava, a herbal remedy for anxiety. BMJ 2001; 322 (7279) 139
  • 109 Bujanda L, Palacios A, Silvariño R, Sánchez A, Muñoz C. [Kava-induced acute icteric hepatitis]. Gastroenterol Hepatol 2002; 25 (6) 434-435
  • 110 Stickel F, Baumüller HM, Seitz K , et al. Hepatitis induced by Kava (Piper methysticum rhizoma). J Hepatol 2003; 39 (1) 62-67
  • 111 Kraft M, Spahn TW, Menzel J , et al. [Fulminant liver failure after administration of the herbal antidepressant Kava-Kava]. Dtsch Med Wochenschr 2001; 126 (36) 970-972
  • 112 Thomsen M, Vitetta L, Schmidt M, Sali A. Fatal fulminant hepatic failure induced by a natural therapy containing kava. Med J Aust 2004; 180 (4) 198-199 , author reply 199
  • 113 Ulbricht C, Basch E, Boon H , et al. Safety review of kava (Piper methysticum) by the Natural Standard Research Collaboration. Expert Opin Drug Saf 2005; 4 (4) 779-794
  • 114 Han D, Matsumaru K, Rettori D, Kaplowitz N. Usnic acid-induced necrosis of cultured mouse hepatocytes: inhibition of mitochondrial function and oxidative stress. Biochem Pharmacol 2004; 67 (3) 439-451
  • 115 Durazo FA, Lassman C, Han SH , et al. Fulminant liver failure due to usnic acid for weight loss. Am J Gastroenterol 2004; 99 (5) 950-952
  • 116 Favreau JT, Ryu ML, Braunstein G , et al. Severe hepatotoxicity associated with the dietary supplement LipoKinetix. Ann Intern Med 2002; 136 (8) 590-595
  • 117 Yellapu RK, Mittal V, Grewal P, Fiel M, Schiano T. Acute liver failure caused by 'fat burners' and dietary supplements: a case report and literature review. Can J Gastroenterol 2011; 25 (3) 157-160
  • 118 Fallon MB, Boyer JL. Hepatic toxicity of vitamin A and synthetic retinoids. J Gastroenterol Hepatol 1990; 5 (3) 334-342
  • 119 Geubel AP, De Galocsy C, Alves N, Rahier J, Dive C. Liver damage caused by therapeutic vitamin A administration: estimate of dose-related toxicity in 41 cases. Gastroenterology 1991; 100 (6) 1701-1709
  • 120 Lucena MI, Molokhia M, Shen Y , et al; Spanish DILI Registry; EUDRAGENE; DILIN; DILIGEN; International SAEC. Susceptibility to amoxicillin-clavulanate-induced liver injury is influenced by multiple HLA class I and II alleles. Gastroenterology 2011; 141 (1) 338-347
  • 121 Daly AK, Donaldson PT, Bhatnagar P , et al; DILIGEN Study; International SAE Consortium. HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nat Genet 2009; 41 (7) 816-819
  • 122 Lin G, Wang JY, Li N , et al. Hepatic sinusoidal obstruction syndrome associated with consumption of Gynura segetum. J Hepatol 2011; 54 (4) 666-673
  • 123 De Berardinis V, Moulis C, Maurice M , et al. Human microsomal epoxide hydrolase is the target of germander-induced autoantibodies on the surface of human hepatocytes. Mol Pharmacol 2000; 58 (3) 542-551
  • 124 Yang HN, Kim DJ, Kim YM , et al. Aloe-induced toxic hepatitis. J Korean Med Sci 2010; 25 (3) 492-495
  • 125 AEMPS. Retirada de los productos episdrol y epistane. In: SANITARIOS) AAEDMYP ed. Ministerio de sanidad, servicios sociales e igualdad; 2013 . Available at: http://www.aemps.gob.es/informa/notasInformativas/medicamentosUsoHumano/medIlegales/2013/docs/ICM_MI_09-2013-episdrol-epistane.pdf . Accessed January 14, 2014
  • 126 Nadir A, Reddy D, Van Thiel DH. Cascara sagrada-induced intrahepatic cholestasis causing portal hypertension: case report and review of herbal hepatotoxicity. Am J Gastroenterol 2000; 95 (12) 3634-3637
  • 127 Kao WF, Hung DZ, Tsai WJ, Lin KP, Deng JF. Podophyllotoxin intoxication: toxic effect of Bajiaolian in herbal therapeutics. Hum Exp Toxicol 1992; 11 (6) 480-487
  • 128 European Medicines Agency. Assessment Report on Cimicifuga racemosa (L.) Nutt. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_HMPC_assessment_report/2011/05/WC500106358.pdf . Accessed January 14, 2014
  • 129 de Sanidad M, Sociales e Igualdad S. AEMPS. Extracto de la raíz de “Cimicifuga racemosa” y lesiones hepaticas. Available at: http://www.aemps.gob.es/informa/notasInformativas/medicamentosUsoHumano/seguridad/2006/docs/NI_2006-06_cimicifuga.pdf . Accessed January 14, 2014
  • 130 European Medicines Agency. Assessment report on Peumus boldus Molina, folium. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_HMPC_assessment_report/2009/12/WC500018102.pdf . Accessed January 14, 2014
  • 131 Piscaglia F, Leoni S, Venturi A, Graziella F, Donati G, Bolondi L. Caution in the use of boldo in herbal laxatives: a case of hepatotoxicity. Scand J Gastroenterol 2005; 40 (2) 236-239
  • 132 Sohni YR. The toxicity of Callilepis laureola, a South African traditional herbal medicine. Clin Biochem 2002; 35 (6) 499
  • 133 AEMPS. Suspension de comercialización de la especialidad farmacéutica Exolise®: Extracto etanolico de camelia sinensis (te verde). Available at: http://www.aemps.gob.es/informa/notasInformativas/medicamentosUsoHumano/seguridad/2003/NI_2003-03_exolise.htm . Accessed January 13, 2014
  • 134 Jimenez JF, Brown AL, Arnold WC, Byrne WJ. Chronic camphor ingestion mimicking Reye's syndrome. Gastroenterology 1983; 84 (2) 394-398
  • 135 Uc A, Bishop WP, Sanders KD. Camphor hepatotoxicity. South Med J 2000; 93 (6) 596-598
  • 136 Jorge OA, Jorge AD. Hepatotoxicity associated with the ingestion of Centella asiatica. Rev Esp Enferm Dig 2005; 97 (2) 115-124
  • 137 Benninger J, Schneider HT, Schuppan D, Kirchner T, Hahn EG. Acute hepatitis induced by greater celandine (Chelidonium majus). Gastroenterology 1999; 117 (5) 1234-1237
  • 138 Adachi M, Saito H, Kobayashi H , et al. Hepatic injury in 12 patients taking the herbal weight loss AIDS Chaso or Onshido. Ann Intern Med 2003; 139 (6) 488-492
  • 139 Yuen MF, Tam S, Fung J, Wong DK, Wong BC, Lai CL. Traditional Chinese medicine causing hepatotoxicity in patients with chronic hepatitis B infection: a 1-year prospective study. Aliment Pharmacol Ther 2006; 24 (8) 1179-1186
  • 140 Shah M, Williams C, Aggarwal A, Choudhry WM. Licorice-related rhabdomyolysis: a big price for a sweet tooth. Clin Nephrol 2012; 77 (6) 491-495
  • 141 Bruguera M, Herrera S, Lázaro E, Madurga M, Navarro M, de Abajo FJ. [Acute hepatitis associated with Colpachi intake. Apropros of 5 cases]. Gastroenterol Hepatol 2007; 30 (2) 66-68
  • 142 Abraham K, Wöhrlin F, Lindtner O, Heinemeyer G, Lampen A. Toxicology and risk assessment of coumarin: focus on human data. Mol Nutr Food Res 2010; 54 (2) 228-239
  • 143 Hernández S, di Pace F, Bessone M , et al. Espectro de la Hepatotoxicidad en Latinoamérica: Fundación y Resultados iniciales del Registro Español-. Latinoamericano de Hepatotoxicidad. Gastroenterol Hepatol 2013; 36 (Suppl. 01) 27-97
  • 144 Jacobsson I, Jönsson AK, Gerdén B, Hägg S. Spontaneously reported adverse reactions in association with complementary and alternative medicine substances in Sweden. Pharmacoepidemiol Drug Saf 2009; 18 (11) 1039-1047
  • 145 Werneke U, Earl J, Seydel C, Horn O, Crichton P, Fannon D. Potential health risks of complementary alternative medicines in cancer patients. Br J Cancer 2004; 90 (2) 408-413
  • 146 Gori L, Galluzzi P, Mascherini V , et al. Two contemporary cases of hepatitis associated with Teucrium chamaedrys L. decoction use: case reports and review of literature. Basic Clin Pharmacol Toxicol 2011; 109 (6) 521-526
  • 147 Anderson IB, Mullen WH, Meeker JE , et al. Pennyroyal toxicity: measurement of toxic metabolite levels in two cases and review of the literature. Ann Intern Med 1996; 124 (8) 726-734
  • 148 De Smet PA, Van den Eertwegh AJ, Lesterhuis W, Stricker BH. Hepatotoxicity associated with herbal tablets. BMJ 1996; 313 (7049) 92
  • 149 Stadlbauer V, Weiss S, Payer F, Stauber RE. Herbal does not at all mean innocuous: the sixth case of hepatotoxicity associated with morinda citrifolia (noni). Am J Gastroenterol 2008; 103 (9) 2406-2407
  • 150 Ueng YF, Hsieh CH, Don MJ. Inhibition of human cytochrome P450 enzymes by the natural hepatotoxin safrole. Food Chem Toxicol 2005; 43 (5) 707-712
  • 151 Hamid S, Rojter S, Vierling J. Protracted cholestatic hepatitis after the use of prostata. Ann Intern Med 1997; 127 (2) 169-170
  • 152 Wiwanitkit V. Excessive consumption of soybean milk and unexplained hepatitis. J Postgrad Med 2012; 58 (3) 226-227
  • 153 Secretaria de Salud de Mexico. COFEPRIS. Comunicado a los consumidores del producto CAPSLIM. Available at: http://www.cofepris.gob.mx/AZ/Documents/COMUNICADOCAPSLIM.pdf . Accessed January 14, 2014
  • 154 Harvey J, Colin-Jones DG. Mistletoe hepatitis. Br Med J (Clin Res Ed) 1981; 282 (6259) 186-187
  • 155 Soares MdoC. Would Sacaca, Croton cajucara Benth (Euphorbiaceae) be an hepatotoxic plant like Germander, Teucrium chamaedrys L. (Labiatae)?. Rev Soc Bras Med Trop 2004; 37 (Suppl. 02) 96-97