Hepatitis induced by Kava (Piper methysticum rhizoma)

Stickel, Felix; Baumüller, Hans-Martin; Seitz, Karlheinz; Vasilakis, D; Seitz, Gerhard; Seitz, Helmut K.; Schuppan, Detlef

doi:10.1016/s0168-8278(03)00175-2

Cited by 155 publications

(86 citation statements)

References 27 publications

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“…The types of liver damage include hepatitis, cirrhosis, liver failure, and death (31,(46)(47)(48)(49)(50)(51). It is not clear what doses were used and the period of use associated with the risk of liver damage.…”

Section: Human Datamentioning

confidence: 99%

Toxicity of Kava Kava

Xia

Guo

et al. 2008

Journal of Environmental Science and Health, Part C

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Kava is a traditional beverage of various Pacific Basin countries. Kava has been introduced into the mainstream U.S. market principally as an anti-anxiety preparation. The effects of the long-term consumption of kava have not been documented adequately. Preliminary studies suggest possible serious organ system effects. The potential carcinogenicity of kava and its principal constituents are unknown. As such, kava extract was nominated for the chronic tumorigenicity bioassay conducted by the National Toxicology Program (NTP). At present toxicological evaluation of kava extract is being conducted by the NTP. The present review focuses on the recent findings on kava toxicity and the mechanisms by which kava induces hepatotoxicity. KeywordsKava; anti-anxiety herbal beverage; top-selling botanical; hepatotoxicity; metabolism; mechanism Kava, prepared from the rhizome of the kava tropical shrub plant, Piper methysticum Forst F., is a traditional beverage used for many centuries, especially at ceremonial activities in the South Pacific (1-6). During recent years, kava has been used in Europe for treatment of anxiety and nervous disorders such as stress and restlessness, and in the United States as a natural alternative to anti-anxiety drugs and sleeping pills (6). Kava sales totaled more than $ 100 million in 1998, being the fifth leading seller of the North American botanicals (7).The association between the use of kava products and hepatotoxicity has prompted many countries, including Germany, Switzerland, France, Canada, and the United Kingdom, to take regulatory actions, ranging from warning consumers to removing kava-containing products from the marketplace. On March 25, 2002, the Center for Food Safety and Applied Nutrition (CFSAN), U.S. Food and Drug Administration (FDA) issued a Consumer Advisory entitled "Kava-containing dietary supplements may be associated with severe liver injury" to the public (8, 9). Kava-containing products remain popular in the United States and continue to be sold in health food stores and ethnic markets regardless of the fact that it Address correspondence to Peter P. Fu, National Center for Toxicological Research, Jefferson, AR 72079. peter.fu@fda.hhs.gov; chanp@niehs.nih.gov. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript was banned in Germany, France, Switzerland, Australia, and Canada (10). In this review, human exposure and metabolism of kava are briefly addressed, recent findings on the toxicity of kava are reported, and possible mechanisms by which kava induces toxicity are described. CHEMICAL COMPOSITIONThe kava plant, belonging to the Piperacae family, is widely cultivated in the South Pacific.Kava is cultivated for its rootstock. Depending upon the amount of kavalactones contained in the resin, the rootstock shows different color, varying from white to dark yellow (2,5,6). Fresh kava rootstock contains about 80% water. Dried rootstock consists of about 43% starch, 20% fibers, 12% water, 3-4% proteins, 3% sugars, 3% minerals, ...

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Section: Human Datamentioning

confidence: 99%

Toxicity of Kava Kava

Xia

Guo

et al. 2008

Journal of Environmental Science and Health, Part C

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“…The TTK scale is widely used in Japan [74] , as recently reviewed [75] . In other countries, this scale is not or rarely [59] Kava 20 Teschke et al [60] Kava 36 Stickel et al [61] Kava 80 Schmidt et al [62] Greater Celandine 23 BfArM [63] Black cohosh 31 EMA [54] Herbalife products 12 Elinav et al [64] Herbalife products 12 Schoepfer et al [65] Kava 26 Teschke et al [12] Black cohosh 30 Mahady et al [42] Green tea 34 Sarma et al [43] Black cohosh 4 Teschke et al [47] Black cohosh 9 Teschke et al [48] Kava 31 Teschke [34] Hydroxycut 17 Fong et al [66] Black cohosh 22 Teschke et al [36] Greater Celandine 22 Teschke et al [37] Herbalife products 20 Manso et al [67] Various herbs 45 Chau et al [57] Greater Celandine 21 Teschke et al [32] Pelargonium sidoides 15 Teschke et al [38] Pelargonium sidoides 13 Teschke et al [39] Sum ( The data are derived from a study evaluating alternative causes in suspected HILI cases (n = 573) comprising the study cohort [5] . For the 275 CIOMS cases, causality assessment was performed with the updated CIOMS scale the original CIOMS scale, or both.…”

Section: Other Liver Specific Methodsmentioning

confidence: 99%

“…Among various causality assessment methods, the original and updated CIOMS scales were the preferred tools in cases of DILI [28] and HILI (Table 8) [5] , seen for 573 cases from 23 HILI reports evaluating alternative causes [12,32,34,[36][37][38][39]42,43,47,48,54,[57][58][59][60][61][62][63][64][65][66][67] . Transparency CIOMS based assessments should be reported or published as an original data set suitable for subsequent and independent assessments, rather than as final scores and corresponding causality levels, to improve data transparency.…”

Section: Usage Frequencymentioning

confidence: 99%

Drug and herb induced liver injury: Council for International Organizations of Medical Sciences scale for causality assessment

Teschke

Wolff

Frenzel

et al. 2014

WJH

109

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Causality assessment of suspected drug induced liver injury (�ILI) and herb induced liver injury (HILI) is hampered by the lack of a standardized approach to be used by attending physicians and at various subsequent evaluating levels. The aim of this review was to analyze the suitability of the liver specific Council for International Organizations of �edical Sciences (CIO�S) scale as a standard tool for causality assessment in �ILI and HILI cases. �ub�ed database was searched for the following terms: drug induced liver injury; herb induced liver injury; �ILI causality assessment; and HILI causality assessment. The strength of the CIO�S lies in its potential as a standardized scale for �ILI and HILI causality assessment. Other advantages include its liver specificity and its validation for hepatotoxicity with excellent sensitivity, specificity and predictive validity, based on cases with a positive reexposure test. This scale allows prospective collection of all relevant data required for a valid causality assessment. It does not require expert knowledge in hepatotoxicity and its results may subsequently be refined. Weaknesses of the CIO�S scale include the limited exclusion of alternative causes and qualitatively graded risk factors. In conclusion, CIO�S appears to be suitable as a standard scale for attending physicians, regulatory agencies, expert panels and other scientists to provide a standardized, reproducible causality assessment in suspected �ILI and HILI cases, applicable primarily at all assessing levels involved.© 2014 Baishideng �ublishing Group Co., Limited. All rights reserved.Key words: �rug induced liver injury; �rug hepatotoxicity; Herb induced liver injury; Herbal hepatotoxicity; Causality assessment Core tip: We propose that the attending physicians caring for patients with assumed drug induced liver injury and herb induced liver injury should use the Council for International Organizations of �edical Sciences (CIO�S) scale for causality assessment. This approach includes the option of subsequent refinement of the CIO�S based results by expert panels and regulatory agencies. The use of the CIO�S scale as an identical

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“…Following numerous cases of fulminant liver failure leading to liver transplantation and death, kava products were banned in the USA, Europe and Australia (Centers for Disease Control and Prevention 2003). Although clinical presentation was considerably variable, causality assessment left little doubt that kava was the cause in a majority of a series of 29 cases of adverse hepatic reactions due to kava in Germany (Stickel et al 2003). Among these patients, nine developed fulminant liver failure with subsequent liver transplantation in eight of the patients, and three died eventually.…”

mentioning

confidence: 99%

Response to Aghdassi et al., Letter to the editor “Genetic polymorphisms in the UDP-glucuronosyltransferase UGT1A7 gene in patients with acute liver failure after kava–kava consumption”

Hepatitis induced by Kava (Piper methysticum rhizoma)

Cited by 155 publications

References 27 publications

Toxicity of Kava Kava

Toxicity of Kava Kava

Drug and herb induced liver injury: Council for International Organizations of Medical Sciences scale for causality assessment

Response to Aghdassi et al., Letter to the editor “Genetic polymorphisms in the UDP-glucuronosyltransferase UGT1A7 gene in patients with acute liver failure after kava–kava consumption”

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