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DOI: 10.1055/s-2002-30104
Herbal Hepatotoxicity
Publication History
Publication Date:
16 May 2002 (online)
ABSTRACT
Herbal hepatotoxicity is increasingly recognized as herbal medicines become more popular in industrialized societies. Some herbal products may potentially benefit people with liver disease; however, these benefits remain generally unproved in humans, and a greater awareness of potential adverse effects is required. Herbal use is often not disclosed, and this may result in a diagnostic delay and perpetuation or exacerbation of liver injury. Female gender may predispose to hepatotoxicity, and concomitant agents that induce cytochrome P450 enzymes may also increase individual susceptibility. The range of liver injury includes minor transaminase elevations, acute and chronic hepatitis, steatosis, cholestasis, zonal or diffuse hepatic necrosis, hepatic fibrosis and cirrhosis, veno-occlusive disease, and acute liver failure requiring transplantation. In addition to the potential for hepatotoxicity, drug-drug interactions between herbal medicines and conventional agents may affect the efficacy and safety of concurrent medical therapy. This review focuses on emerging hepatotoxins and patterns of liver injury, potential risk factors for herbal hepatotoxicity, and herb-drug interactions. Appropriate reporting and regulatory systems to monitor herbal toxicity are required, in conjunction with ongoing scientific evaluation of the potential benefits of phytotherapy.
KEYWORDS
Herbal medicine - Chinese herbal drugs - liver injury - drug-drug interactions
REFERENCES
- 1 Kessler R C, Davis R B, Foster D F. Long-term trends in the use of complementary and alternative medical therapies in the United States. Ann Intern Med . 2001; 135 262-268
- 2 Seef L B, Lindsay K L, Bacon B R. Complementary and alternative medicine in chronic liver disease. Hepatology . 2001; 34 595-603
- 3 Berk B S, Chaya C, Benner K C, Flora K D. Comparison of herbal therapy for liver disease: 1996 versus 1999. Hepatology . 1999; 30 478A
- 4 Schuppan D, Jia J-D, Brinkhaus B, Hahn E G. Herbal products for liver diseases: a therapeutic challenge for the new millennium. Hepatology . 1999; 30 1099-1104
- 5 Eisenberg D M, Kessler R C, Van Rompay I M. Perceptions about complementary therapies relative to conventional therapies among adults who use both: results from a national survey. Ann Intern Med . 2001; 135 344-351
- 6 Borum M L. Fulminant exacerbation of autoimmune hepatitis after the use of Ma huang. Am J Gastroenterol . 2001; 96 1654-1655
- 7 Kamiyama T, Nouchi T, Kojima S. Autoimmune hepatitis triggered by administration of an herbal medicine. Am J Gastroenterol . 1997; 92 703-704
- 8 Fau D, Lekehal M, Farrell G. Diterpenoids from germander, an herbal medicine, induce apoptosis in isolated rat hepatocytes. Gastroenterology . 1997; 113 1334-1346
- 9 Kaplowitz N. Hepatotoxicity of herbal remedies: insights into the intricacies of plant-animal warfare and cell death. Gastroenterology . 1997; 113 1408-1409
- 10 Haouzi D, Lekehal M, Moreau A. Cytochrome P450-generated reactive metabolites cause mitochondrial permeability transition, caspase activation, and apoptosis in rat hepatocytes. Hepatology . 2000; 32 303-311
- 11 Cheng T O. Warfarin danshen interaction. Ann Thorac Surg . 1999; 67 892-896
- 12 Fugh-Berman A. Herb-drug interactions. Lancet . 2000; 355 134-138
- 13 Shaw D, Leon C, Kolev S, Murray V. Traditional remedies and food supplements: a five year toxicological study. Drug Saf . 1997; 17 342-356
- 14 Page R L, Lawrence J D. Potentiation of warfarin by dong quai. Pharmacotherapy . 1999; 19 870-876
- 15 Ellis G R, Stephens M R. Untitled (photographs and brief case report). BMJ . 1999; 319 650
- 16 Miller L G. Herbal medicinals: selected clinical considerations focussing on known or potential drug-herb interactions. Arch Intern Med . 1998; 158 2200-2211
- 17 Rose K D, Croissant P D, Parliament C F, Levin M B. Spontaneous spinal epidural hematoma with associated platelet dysfunction from excessive garlic ingestion: a case report. Neurosurgery . 1990; 26 880-882
- 18 Lamant V, Mauco G, Braquet P. Inhibition of the metabolism of platelet activating factor (PAF-acether) by three specific antagonists from Ginkgo biloba. Biochem Pharmacol . 1987; 36 2749-2752
- 19 Vale S. Subarachnoid haemorrhage associated with Ginkgo biloba Lancet . 1998; 352 36
- 20 Fessenden J M, Wittenborn W, Clarke L. Ginkgo biloba: a case report of herbal medicine and bleeding postoperatively from a laparoscopic cholecystectomy. Am Surg . 2001; 67 33-35
- 21 Skogh M. Extracts of Ginkgo biloba and bleeding or haemorrhage. Lancet . 1998; 352 1145-1146
- 22 Janetzky K, Morreale A P. Probable interaction between warfarin and ginseng. Am J Health Syst Pharm . 1997; 54 692-693
- 23 Yue Q-Y, Bergquist C, Gerden B. Safety of St John's wort (Hypericum perforatum). Lancet . 2000; 355 576-577
- 24 Mustapha A, Yakasai I A, Aguye I A. Effect of Tamarindus indica L. on the bioavailability of aspirin in healthy human volunteers. Eur J Drug Metab Pharmacokinet . 1996; 21 223-226
- 25 Karliova M, Treichel U, Malago M. Interaction of Hypericum perforatum (St John's wort) with cyclosporin A metabolism in a patient after liver transplantation. J Hepatol . 2000; 33 853-855
- 26 Stickel F, Egerer G, Seitz H K. Hepatotoxicity of botanicals. Public Health Nutr . 2000; 3 113-124
- 27 Loeper J, Descatoire V, Letteron P. Hepatotoxicity of germander in mice. Gastroenterology . 1994; 106 464-472
- 28 Chen M F, Shimada F, Kato H. Effect of oral administration of glycyrrhizin on the pharmacokinetics of prednisolone. Endocrinol Jpn . 1991; 38 167-174
- 29 Homma M, Oka K, Ikeshima K. Different effects of traditional Chinese medicines containing similar herbal constituents on prednisolone pharmacokinetics. J Pharm Pharmacol . 1995; 47 687-692
- 30 Moore L B, Goodwin B, Jones S A. St John's wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proc Natl Acad Sci USA . 2000; 97 7500-7502
- 31 Durr D, Stieger B, Kullak-Ublick G A. St John's wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4. Clin Pharmacol Ther . 2000; 68 598-604
- 32 Chitturi S, Farrell G. Herbal hepatotoxicity: an expanding but poorly defined problem. J Gastroenterol Hepatol . 2000; 15 1093-1099
- 33 Larrey D. Hepatotoxicity of herbal remedies. J Hepatol . 1997; 26 47-51
- 34 Farrell G C, Weltman M. Drug-induced liver disease. In: Gitnick G, ed. Current Hepatology, vol 16 Chicago: Mosby- Year Book Medical Publishers 1996: 143-208
- 35 Farrell G C. Drug-Induced Liver Disease. Edinburgh: Churchill Livingstone 1994: 513-518
- 36 Uc A, Bishop W P, Sanders K D. Camphor hepatotoxicity. South Med J . 2000; 93 596-598
- 37 Jimenez J F, Brown A L, Arnold W C, Byrne W J. Chronic camphor ingestion mimicking Reye's syndrome. Gastroenterology . 1983; 84 394-398
- 38 Lin Y F, Lin S H. Simultaneous acute renal and hepatic failure after ingesting raw carp gall bladder. Nephrol Dial Transplant . 1999; 14 2011-2012
- 39 Nadir A, Reddy D, Van Thiel H D. Cascara sagrada-induced intrahepatic cholestasis causing portal hypertension: case report and review of herbal hepatotoxicity. Am J Gastroenterol . 2000; 95 3634-3637
- 40 Sheikh N M, Philen R M, Love L A. Chaparral-associated hepatotoxicity. Arch Intern Med . 1997; 157 913-919
- 41 Batchelor W B, Heathcote J, Wanless I R. Chaparral-induced hepatic injury. Am J Gastroenterol . 1995; 90 831-832
- 42 Kane J A, Kane S P, Jain S. Hepatitis induced by traditional Chinese herbs; possible toxic components. Gut . 1995; 36 146-147
- 43 Yoshida E M, McLean C A, Cheng E S. Chinese herbal medicine, fulminant hepatitis and liver transplantation (letter). Am J Gastroenterol . 1996; 91 2647-2648
- 44 Itoh S, Marutani K, Nishijima T. Liver injuries induced by herbal medicine, syo-saiko-to (xiao-chai-hu-tang). Dig Dis Sci . 1995; 40 1845-1848
- 45 Benninger J, Schneider H T, Schuppan D. Acute hepatitis induced by greater celandine (Chelidonium majus). Gastroenterology . 1999; 117 1234-1237
- 46 Mostefa-Kara N, Pauwels A, Pines E. Fatal hepatitis after herbal tea (letter). Lancet . 1992; 340 674
- 47 Larrey D, Vial T, Pauwels A. Hepatitis after germander (Teucrium chamaedrys) administration: another instance of herbal medicine hepatotoxicity. Ann Intern Med . 1992; 117 129-132
- 48 Popat A, Shear N H, Malkiewicz I. The toxicity of Callilepis laureola, a South African traditional herbal medicine. Clin Biochem . 2001; 34 229-236
- 49 Fraquelli M, Colli A, Cocciolo M, Conte D. Adult syncytial giant cell chronic hepatitis due to herbal remedy. J Hepatol . 2000; 33 505-508
- 50 Picciotto A, Campo N, Brizzolara R. Chronic hepatitis induced by Jin Bu Huan. J Hepatol . 1998; 28 165-167
- 51 Horowitz R S, Feldhaus K, Dart R C. The clinical spectrum of Jin Bu Huan toxicity. Arch Intern Med . 1996; 156 899-903
- 52 Woolf G M, Petrovic L M, Rojter S E. Acute hepatitis associated with the Chinese herbal product Jin Bu Huan. Ann Intern Med . 1994; 121 729-735
- 53 Escher M, Desmeales J, Giostra E, Mentha G. Hepatitis associated with Kava, a herbal remedy for anxiety. BMJ . 2001; 322 139
- 54 Kraft M, Spahn T W, Menzel J. Fulminantes Leberversagen nach Einnahme des pflanzlichen antidepressivums kava-kava. Dtsch Med Wochenschr . 2001; 126 970-972
- 55 Russmann S, Lauterburg B H, Helbling A. Kava hepatotoxicity. Ann Intern Med . 2001; 135 68-69
- 56 Perron A D, Patterson J A, Yanofsky N N. Kombucha ``mushroom'' hepatotoxicity (letter). Ann Emerg Med . 1995; 26 660-661
- 57 Tolman K G, Hammar S, Sannella J J. Possible hepatotoxicity of Doxidan. Ann Intern Med . 1976; 84 290-292
- 58 Beuers U, Spengler V, Pape G R. Hepatitis after chronic abuse of senna (letter). Lancet . 1991; 37 372
- 59 Woolf G M. Senna-induced hepatotoxicity. Hepatology . 1999; 550A 1560
- 60 Nadir A, Agarwal S, King P D, Marshall J B. Acute hepatitis associated with the use of a Chinese herbal product, Ma-huang. Am J Gastroenterol . 1996; 91 1436-1438
- 61 Stewart M J, Steenkamp V. The biochemistry and toxicity of atractyloside: a review. Ther Drug Monit . 2000; 22 641-649
- 62 Mattei A, Rucay P, Samuel D. Liver transplantation for acute liver failure after herbal medicine (Teucrium polium) administration (letter). J Hepatol . 1995; 22 597
- 63 Harvey J, Colin-Jones D G. Mistletoe hepatitis. BMJ . 1981; 282 1050-1054
- 64 Harvey J, Colin-Jones D G. Mistletoe hepatitis. Br Med J (Clin Res Ed) . 1981; 282 186-187
- 65 Anderson I B, Mullen W H, Meeker J E. Pennyroyal toxicity: measurement of toxic metabolites in two cases and review of the literature. Ann Intern Med . 1996; 124 726-734
- 66 Bakerink J A, Gosper S M, Dimand R J, Eldridge M W. Multiple organ failure after ingestion of pennyroyal oil from herbal tea in two infants. Pediatrics . 1996; 98 944-947
- 67 Hamid S, Rojter S, Vierling J. Protracted cholestatic hepatitis after the use of Prostata (letter). Ann Intern Med . 1997; 127 169-170
- 68 Ashar B, Vargo E. Shark cartilage-induced hepatitis. Ann Intern Med . 1996; 125 780-781
- 69 Park G JH, Mann S P, Ngu M C. Acute hepatitis induced by Shou-Wu-Pian, a herbal product derived from Polygonum multiflorum J Gastroenterol Hepatol . 2001; 16 115-117
- 70 But P P, Tomlinson B, Lee K L. Hepatitis related to the Chinese medicine Shou-wu-pian manufactured from Polygonum multiflorum Vet Hum Toxicol . 1996; 38 280-282
- 71 Steenkamp V, Stewart M, Zuckerman M. Clinical and analytical aspects of pyrrolizidine alkaloid poisoning caused by South African traditional medicines. Ther Drug Monit . 2000; 22 302-306
- 72 De Smet P G M A, Van den Eertwegh J M A, Lesterhuis W. Hepatotoxicity associated with herbal tablets. BMJ . 1996; 313 92
- 73 Takegoshi, Tohyama T, Cox D. Hepatotoxicity associated with herbal tablets (letter). BMJ . 1996; 313 92
- 74 Zimmerman H J. Drug-induced liver disease. Clin Liver Dis . 2000; 4 73-96
- 75 Khojasteh-Bakht S C, Chen W, Koenigs L L. Metabolism of (R)+-pulegone and (R)-+-menthofuran by human liver cytochrome P450s: evidence for formation of a furan epoxide. Drug Metab Dispos . 1999; 27 574-580
- 76 Ben Yahia M, Mavier P, Metreau J M. Hépatite chronique active et cirrhose induites par la germandree petit-chêne. Trois cas. Gastroenterol Clin Biol . 1993; 17 959-962
- 77 Perharic-Walton L, Murray V. Toxicity of Chinese herbal remedies. Lancet . 1992; 340 674
- 78 Hullar T E, Sapers B L, Ridker P M. Herbal toxicity and fatal hepatic failure. Am J Med . 1999; 106 267-268
- 79 DeLeve L D, McCuskey R S, Wang X. Characterization of a reproducible rat model of hepatic veno-occlusive disease. Hepatology . 1999; 29 1779-1791
- 80 Wang X, Kanel G C, DeLeve L D. Support of sinusoidal endothelial cell glutathione prevents hepatic veno-occlusive disease in the rat. Hepatology . 2000; 31 428-434
- 81 Laliberte L, Villeneuve J P. Hepatitis after use of germander, a herbal remedy. Can Med Assoc J . 1996; 154 1689-1692
- 82 Alvarez P, Saez-Royuela F, Pena G. Acute hepatitis due to ingestion of Teucrium chamaedrys infusions. Gastroenterol Hepatol . 2001; 24 240-243
- 83 Lekehal M, Pessayre D, Lereau J M. Hepatotoxicity of the herbal medicine germander: metabolic activation of its furano diterpenoids by cytochrome P4503A depletes cytoskeleton-associated protein thiols and forms plasma membrane blebs in rat hepatocytes. Hepatology . 1996; 24 212-218
- 84 De Berardinis V, Moulis C, Maurice M. Human microsomal epoxide hydrolase is the target of germander-induced autoantibodies on the surface of human hepatocytes. Mol Pharmacol . 2000; 58 542-551
- 85 Melchart D, Linde K, Weidenhammer W. Liver enzyme elevation in patients treated with traditional Chinese medicine. JAMA . 1999; 282 28-29
- 86 Grahan-Brown R. Toxicity of Chinese herbal remedies (letter). Lancet . 1992; 340 673
- 87 Gorey J D, Wahlqvist M L, Boyce N W. Adverse reaction to a Chinese herbal remedy. Med J Aust . 1992; 157 484-486
-
88 Chitturi S, Farrell G C. Drug induced liver disease. In: Sorrell MF, Schiff ER, eds. Schiff's Diseases of the Liver, 9th ed Philadelphia: Lippincott Williams & Wilkins; 2002 (in press)
- 89 Shimizu I. Sho-saiko-to: Japanese herbal medicine for protection against hepatic fibrosis and carcinoma. J Gastroenterol Hepatol . 2000; 15(Suppl) D84-D90
- 90 MacGregor F B, Abernethy V E, Dahabra S. Hepatotoxicity of herbal remedies. BMJ . 1989; 199 1156-1157
- 91 Smith B C, Desmond P V. Acute hepatitis induced by ingestion of the herbal medicine chaparral. Aust N Z J Med . 1993; 23 526
- 92 Strahl S, Ehret V, Dahm H H, Maier K P. Necrotizing hepatitis after taking herbal remedies. [Article in German] Dtsch Med Wochenschr . 1998; 123 1410-1414