Clinical and causality assessment in herbal hepatotoxicity

Teschke, Rolf; Schwarzenboeck, Alexander; Eickhoff, Axel; Frenzel, Christian; Wolff, Albrecht; Schulze, Johannes

doi:10.1517/14740338.2013.774371

Cited by 58 publications

(140 citation statements)

References 80 publications

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“…Using specific and established criteria for reexposure tests (Table 3) [16,31] , reexposure results in the study group were positive in one patient, negative in another patient, and uninterpretable in six patients (Table 4). Subsequent liver specific causality assessments using the CIOMS scale showed much lower causality levels than published before; they now were probable (n = 1), unlikely (n = 4), or even excluded (n = 3) ( Tables 1 and 5).…”

Section: Discussionmentioning

confidence: 99%

“…A positive reexposure test is commonly considered as gold standard to establish causality for hepatotoxicity [1][2][3][4][5][31][32][33][34][35] , provided specific and well established criteria are fulfilled [31][32][33][34] . A preliminary study revealed that in 17/30 cases of herbal hepatotoxicity with initially positive reexposure tests the presented data did not fulfil core criteria of a positive reexposure test or that the quality of case data was insufficient and led to uninterpretable results [16] . In this study, case data with assumed Herbalife hepatotoxicity and a positive unintentional reexposure test were reevaluated for fulfilment of specific and well established reexposure criteria and for liver specific causality assessments.…”

Section: Introductionmentioning

confidence: 87%

“…These reports created safety concerns and led to editorials [11][12][13] , commentaries [14][15][16] , and critical Letters to the Editor [17][18][19][20][21][22][23][24][25][26][27] , all addressing relevant issues [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] . Speculations about bacterial contamination with Bacillus subtilis in Herbalife products emerged [8,12] , and potentially hepatotoxic ingredients such as green tea extracts, ephedra sinica, aloe, or vitamin A overdose have been proposed as culprits [2][3][4]10] .…”

Section: Introductionmentioning

confidence: 99%

“…In addition, overall case data quality was mixed due to confounding variables, missing firm exclusion of alternative explanations, and the use of problematic causality attribution methods [1][2][3][4][5][6][7][8][9][10] . For hepatotoxicity cases, even with stringent causality assessment the culprits remain undetected in up to 38% of severe liver disease [28] , and alternative causes are frequently found [16,29,30] , with up to 47% in initially assumed drug induced liver injury (DILI) cases [16,29] and with an average of 49% in initially suspected herb induced liver injury (HILI) cases [30] . When adjusted for case duplications, Herbalife hepatotoxicity was suspected in 53 cases [1][2][3][4][5][6][7][8][9][10] .…”

Section: Introductionmentioning

confidence: 99%

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Herbalife hepatotoxicity: Evaluation of cases with positive reexposure tests

Teschke¹,

Frenzel²,

Schulze³

et al. 2013

WJH

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AIM:To analyze the validity of applied test criteria and causality assessment methods in assumed Herbalife hepatotoxicity with positive reexposure tests. METHODS:We searched the Medline database for suspected cases of Herbalife hepatotoxicity and retrieved 53 cases including eight cases with a positive unintentional reexposure and a high causality level for Herbalife. First, analysis of these eight cases focused on the data quality of the positive reexposure cases, requiring a baseline value of alanine aminotransferase (ALT) < 5 upper limit of normal (N) before reexposure, with N as the upper limit of normal, and a doubling of the ALT value at reexposure as compared to the ALT value at baseline prior to reexposure. Second, reported methods to assess causality in the eight cases were evaluated, and then the liver specific Council for International Organizations of Medical Sciences (CIOMS) scale validated for hepatotoxicity cases was used for quantitative causality reevaluation. This scale consists of various specific elements with scores provided through the respective case data, and the sum of the scores yields a causality grading for each individual case of initially suspected hepatotoxicity. RESULTS:Details of positive reexposure test conditions and their individual results were scattered in virtually all cases, since reexposures were unintentional and allowed only retrospective rather than prospective assessments. In 1/8 cases, criteria for a positive reexposure were fulfilled, whereas in the remaining cases the reexposure test was classified as negative (n = 1), or the data were considered as uninterpretable due to missing information to comply adequately with the criteria (n = 6). In virtually all assessed cases, liver unspecific causality assessment methods were applied rather than a liver specific method such as the CIOMS scale. Using this scale, causality gradings for Herbalife in these eight cases were probable (n = 1), unlikely (n = 4), and excluded (n = 3). Confounding variables included low data quality, alternative diagnoses, poor exclusion of important other causes, and comedication by drugs and herbs in 6/8 cases. More specifically, problems were evident in some cases regarding temporal association, daily doses, exact start and end dates of product use, actual data of laboratory parameters such as ALT, and exact dechallenge characteristics. Shortcomings included scattered exclusion of hepatitis A-C, cytomegalovirus and Epstein Barr virus infection with only globally presented or lacking parameters. Hepatitis E virus infection was considered in one single patient and found positive, infections by herpes simplex ORIGINAL ARTICLE

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Herbalife hepatotoxicity: Evaluation of cases with positive reexposure tests

Teschke¹,

Frenzel²,

Schulze³

et al. 2013

WJH

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“…This has been demonstrated by several case reports, case series and literature reviews [1][2][3][4] . However, the potential hepatotoxicity of a variety of chemicals in any herb and case presentations lacking diagnostic exclusion made it difficult to have a clear clinical assessment [5] .…”

Section: Introductionmentioning

confidence: 91%

Lesser celandine (pilewort) induced acute toxic liver injury: The first case report worldwide

Yılmaz

Aktaş

et al. 2014

WJH

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Hepatotoxicity associated with the dietary supplement OxyELITE Pro™ — Hawaii, 2013

Johnston

Chang

Viray

et al. 2015

Drug Testing and Analysis

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Dietary supplements are increasingly marketed to and consumed by the American public for a variety of purported health benefits. On 9 September 2013, the Hawaii Department of Health (HDOH) was notified of a cluster of acute hepatitis and fulminant hepatic failure among individuals with exposure to the dietary supplement OxyELITE Pro™ (OEP). HDOH conducted an outbreak investigation in collaboration with federal partners. Physicians were asked to report cases, defined as individuals with acute onset hepatitis of unknown etiology on or after 1 April 2013, a history of weight-loss/muscle-building dietary supplement use during the 60 days before illness onset, and residence in Hawaii during the period of exposure. Reported cases’ medical records were reviewed, questionnaires were administered, and a product investigation, including chemical analyses and trace back, was conducted. Of 76 reports, 44 (58%) met case definition; of these, 36 (82%) reported OEP exposure during the two months before illness. No other common supplements or exposures were observed. Within the OEP-exposed subset, two patients required liver transplantation, and a third patient died. Excessive product dosing was not reported. No unique lot numbers were identified; there were multiple mainland distribution points, and lot numbers common to cases in Hawaii were also identified in continental states. Product analysis found consumed products were consistent with labeled ingredients; the mechanism of hepatotoxicity was not identified. We report one of the largest statewide outbreaks of dietary supplement-associated hepatotoxicity. The implicated product was OEP. The increasing popularity of dietary supplements raises the potential for additional clusters of dietary supplement-related adverse events.

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Clinical and causality assessment in herbal hepatotoxicity

Abstract: The authors call for substantial improvements in data quality of herbal products and case characteristics and strongly recommend using the CIOMS scale to assess causality in suspected herbal hepatotoxicity.

Cited by 58 publications

References 80 publications

Herbalife hepatotoxicity: Evaluation of cases with positive reexposure tests

Herbalife hepatotoxicity: Evaluation of cases with positive reexposure tests

Lesser celandine (pilewort) induced acute toxic liver injury: The first case report worldwide

Hepatotoxicity associated with the dietary supplement OxyELITE Pro™ — Hawaii, 2013

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