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Cited by 111Drug-Induced Hepatotoxicity and ProtectionComplementary and Alternative Medicine StudiesPlant Toxicity and Pharmacological Properties

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Herbal and Dietary Supplement-Induced Liver Injuries in the Spanish DILI Registry

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Medina-Caliz, Inmaculada, Garcia-Cortes, Miren, Gonzalez-Jimenez, Andres, Cabello, Maria R., Robles-Diaz, Mercedes, Sanabria-Cabrera, Judith, Sanjuan-Jimenez, Rocio, Ortega-Alonso, Aida, García-Muñoz, Beatriz, Moreno, Inmaculada, Jimenez-Perez, Miguel, Fernandez, M Carmen, Ginés, Pere, Prieto, Martin, Conde, Isabel, Hallal, Hacibe, Soriano, German, Roman, Eva, Castiella, Agustin, Blanco-Reina, Encarnacion, Montes, Maria R., Quiros-Cano, Marta, Martin-Reyes, Flores, Lucena, M. Isabel, Andrade, Raul J., Andrade, RJ, Lucena, MI, Stephens, C, García-Cortés, M, Robles-Díaz, M, Medina-Cáliz, I, Sanabria, J, García-Muñoz, B, Alcántara, R, Moreno, I, Gonzalez-Jimenez, A, Ortega-Alonso, A, Sanjuán-Jiménez, R, Quirós, M, Martín-Reyes, F, Papineau, A, Jiménez-Pérez, M, González-Grande, R, Fernández, MC, Peláez, G, Casado, M, González-Sánchez, M, Romero-Gómez, M, Calle-Sanz, R, Millán-Domínguez, R, Fombuena, B, Gallego, R, Rojas, L, Rojas, A, Ampuero, J, del Campo, JA, Gil Gómez, A, Vilar, E, Castiella, A, Zapata, EM, Zubiaurre, L, Navarro, JM, Méndez-Sánchez, IM, Chaves, A, Soriano, G, Guarner, C, Román, EM, Hallal, H, García-Oltra, E, Titos-Arcos, JC, Pérez-Martínez, A, Sánchez-Cobarro, C, Egea-Caparrós, JM, Arenas, J, Gomez-Osua, MI, Gómez-García, A, Esandi, FJ, Blanco, S, Martínez-Odriozola, P, Otazua, P, Salmerón, J, Gila, A, Quiles, R, González, JM, Lorenzo, S, Prieto, M, Conde, I, Amiel, Berenguer, M, García-Eliz, M, Primo, J, Molés, JR, Garayoa, A, Carrascosa, M, Gómez- Domínguez, E, Montané, E, Arellano, AL, Barriocanal, AM, Sanz, Y, Morillas, RM, Sala, M, Masnou, H, Farré, M, Bruguera, M, Gines, P, Lens, S, García, JC, Aldea-Perona, A, Hernández-Guerra, M, Moreno-San Fiel, M, Boada-Fernández del Campo, C, Tejedor, M, González-Ferrer, R, Fernández, C, Fernández-Gil, M, Montero, JL, de la Mata, M, Fuentes-Olmo, J, Fernández-Bonilla, EM, González-Gallego, J, Jorquera, F, Moreno, JM, Martínez-Rodenas, P, Garrido, M, Rendón, P, Vergara, M, Sánchez Delgado, J, García Samaniego, J, Madejón, A, Cabriada, JL, Crespo, J, Giráldez Gallego, A, Cuaresma, M, Ruíz, R·2018·Clinical Gastroenterology and Hepatology
DOI 10.1016/j.cgh.2017.12.051
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Abstract

Background & aims There have been increasing reports of liver injury associated with use of herbal and dietary supplements, likely due to easy access to these products and beliefs among consumers that they are safer or more effective than conventional medications. We aimed to evaluate clinical features and outcomes of patients with herbal and dietary supplement-induced liver injuries included in the Spanish DILI Registry. Methods We collected and analyzed data on demographic and clinical features, along with biochemical parameters, of 32 patients with herbal and dietary supplement-associated liver injury reported to the Spanish DILI registry from 1994 through 2016. We used analysis of variance to compare these data with those from cases of liver injury induced by conventional drugs or anabolic androgenic steroid-containing products. Results Herbal and dietary supplements were responsible for 4% (32 cases) of the 856 DILI cases in the registry; 20 cases of DILI (2%) were caused by anabolic androgenic steroids. Patients with herbal and dietary supplement-induced liver injury were a mean age of 48 years and 63% were female; they presented a mean level of alanine aminotransferase 37-fold the upper limit of normal, 28% had hypersensitivity features, and 78% had jaundice. Herbal and dietary supplement-induced liver injury progressed to acute liver failure in 6% of patients, compared with none of the cases of anabolic androgenic steroid-induced injury and 4% of cases of conventional drugs. Liver injury after repeat exposure to the same product that caused the first DILI episode occurred in 9% of patients with herbal and dietary supplement-induced liver injury vs none of the patients with anabolic androgenic steroid-induced injury and 6% of patients with liver injury from conventional drugs. Conclusion In an analysis of cases of herbal and dietary supplement-induced liver injury in Spain, we found cases to be more frequent among young women than older patients or men, and to associate with hepatocellular injury and high levels of transaminases. Herbal and dietary supplement-induced liver injury is more severe than other types of DILI and re-exposure is more likely. Increasing awareness of the hepatoxic effects of herbal and dietary supplements could help physicians make earlier diagnoses and reduce the risk of serious liver damage.

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  • Herbal drugs and dietary supplements are a major growing concern for liver injury, liver failure, and death or liver transplantation globally.

    “Herbal drugs and dietary supplements are a major growing concern for liver injury, liver failure, and death or liver transplantation globally.3–6”

    From Ashwagandha-induced liver injury—A case series from India and literature review (2023) · cites this paper as [3]

  • Liver-specific causality scales do not capture the complexity of HDS-induced liver injury and are therefore not suitable for attributing causality in that context, because HDS products are frequently multi-ingredient and the toxic compound is often not identified or mislabelled.

    “However, it is important to emphasize that the liver‐specific scales do not capture the complexity of HDS‐induced liver injury and are therefore not suitable for attributing causality in this context, as these products are frequently multi‐ingredient and the toxic compound is often not identified or mislabelled.”

    From Methods for causality assessment of idiosyncratic drug‐induced liver injury (2025) · cites this paper as [3]

  • RECAM is not designed nor tested for HDS liver injury.

    “The RECAM is also not designed nor tested for HDS liver injury which is increasingly reported.20–22”

    From A revised electronic version of RUCAM for the diagnosis of DILI (2022) · cites this paper as [21]

  • Multiple studies from Asia, Europe, and Latin-America have shown that liver injury caused by HMs/HDS is more severe than that caused by other drugs, with a higher risk of death or requirement of liver transplantation.

    “Multiple studies from Asia, Europe, and Latin-America have shown that liver injury caused by HMs/HDS is more severe than that caused by other drugs, with a higher risk of death or requirement of liver transplantation [120,124,134].”

    From Chinese guideline for the diagnosis and treatment of drug-induced liver injury: an update (2024) · cites this paper as [134]

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Research works printed but not linked: 34

  1. 2001, Directive 2001/83/EC of the European Parliament and of the council of 6 November 2001 on the Community code relating to medicinal products for human use, Offic J Eur Union, L311, 67
  2. 2004, Directive 2004/24/EC of the European Parliament and of the Council of 31 March 2004 amending, as regards traditional herbal medicinal products, Directive 2001/83/EC on the Community code relating to medicinal products for human use, Offic J Eur Union, L136, 85
  3. Garcia-Alvarez, 2014, Usage of plant food supplements across six European countries: findings from the PlantLIBRA consumer survey, PLoS One, 9, e92265, 10.1371/journal.pone.0092265 · DOI
  4. Bailey, 2013, Why US adults use dietary supplements, JAMA Intern Med, 173, 355, 10.1001/jamainternmed.2013.2299 · DOI · Paper page
  5. Navarro, 2014, Hepatotoxicity induced by herbal and dietary supplements, Semin Liver Dis, 34, 172, 10.1055/s-0034-1375958 · DOI
  6. Seeff, 2015, Herbal products and the liver: a review of adverse effects and mechanisms, Gastroenterology, 148, 517, 10.1053/j.gastro.2014.12.004 · DOI
  7. Andrade, 2018, Hepatic damage by natural remedies, Semin Liver Dis, 38, 21, 10.1055/s-0038-1623518 · DOI · Paper page
  8. García-Cortés, 2008, Liver injury induced by “natural remedies”: an analysis of cases submitted to the Spanish Liver Toxicity Registry, Rev Esp Enferm Dig, 100, 688
  9. Zhou, 2013, Epidemiology of drug-induced liver injury in China: a systematic analysis of the Chinese literature including 21,789 patients, Eur J Gastroenterol Hepatol, 25, 825, 10.1097/MEG.0b013e32835f6889 · DOI
  10. Suk, 2012, A prospective nationwide study of drug-induced liver injury in Korea, Am J Gastroenterol, 107, 1380, 10.1038/ajg.2012.138 · DOI
  11. Andrade, 2005, Drug-induced liver injury: an analysis of 461 incidences submitted to the Spanish registry over a 10-year period, Gastroenterology, 129, 512, 10.1016/j.gastro.2005.05.006 · DOI
  12. Devarbhavi, 2010, Single-center experience with drug-induced liver injury from India: causes, outcome, prognosis, and predictors of mortality, Am J Gastroenterol, 105, 2396, 10.1038/ajg.2010.287 · DOI · Paper page
  13. Chalasani, 2015, Features and outcomes of 899 patients with drug-induced liver injury: the DILIN prospective study, Gastroenterology, 148, 1340, 10.1053/j.gastro.2015.03.006 · DOI · Paper page
  14. Bessone, 2016, The Latin American DILI registry experience: a successful ongoing collaborative strategic initiative, Int J Mol Sci, 17, 313, 10.3390/ijms17030313 · DOI
  15. Dağ, 2014, Drug- and herb-induced liver injury: a case series from a single center, Turk J Gastroenterol, 25, 41, 10.5152/tjg.2014.4486 · DOI
  16. Hillman, 2016, Clinical features and outcomes of complementary and alternative medicine Induced acute liver failure injury, Am J Gastroenterol, 111, 958, 10.1038/ajg.2016.114 · DOI
  17. Goldberg, 2015, Population-representative incidence of drug-induced acute liver failure based on an analysis of an integrated health care system, Gastroenterology, 148, 1353, 10.1053/j.gastro.2015.02.050 · DOI
  18. Robles-Diaz, 2015, Distinct phenotype of hepatotoxicity associated with illicit use of anabolic androgenic steroids, Aliment Pharmacol Ther, 41, 116, 10.1111/apt.13023 · DOI · Paper page
  19. Benichou, 1990, Criteria of drug-induced liver disorders. Report of an international consensus meeting, J Hepatol, 11, 272, 10.1016/0168-8278(90)90124-A · DOI · Paper page
  20. Aithal, 2011, Case definition and phenotype standardization in drug-induced liver injury, Clin Pharmacol Ther, 89, 806, 10.1038/clpt.2011.58 · DOI
  21. Danan, 1993, Causality assessment of adverse reactions to drugs I. A novel method based on the conclusions of international consensus meeting: application to drug-induced liver injures, J Clin Epidemiol, 43, 1323, 10.1016/0895-4356(93)90101-6 · DOI · Paper page
  22. Bruguera, 2007, Hepatitis aguda asociada al consumo de Copalchi. A propósito de 5 casos, Gastroenterol Hepatol, 30, 66, 10.1157/13099265 · DOI
  23. Navarro, 2017, Liver injury from herbal and dietary supplements, Hepatology, 65, 363, 10.1002/hep.28813 · DOI
  24. 2002, Directive 2002/46/EC of the European Parliament and of the Council of 10 June 2002 on the approximation of the laws of the Member States relating to food supplements, Offic J Eur Union, L183, 51
  25. Douros, 2016, Herb-induced liver injury in the Berlin case-control surveillance study, Int J Mol Sci, 17, E114, 10.3390/ijms17010114 · DOI
  26. Flegal, 2016, Trends in obesity among adults in the United States, 2005 to 2014, JAMA, 315, 2284, 10.1001/jama.2016.6458 · DOI · Paper page
  27. Esteghamati, 2015, Complementary and alternative medicine for the treatment of obesity: a critical review, Int J Endocrinol Metab, 13, e19678, 10.5812/ijem.19678 · DOI
  28. Pillitteri, 2008, Use of dietary supplements for weight loss in the United States: results of a national survey, Obesity, 16, 790, 10.1038/oby.2007.136 · DOI
  29. Robles-Diaz, 2014, Use of Hy's law and a new composite algorithm to predict acute liver failure in patients with drug-induced liver injury, Gastroenterology, 147, 109, 10.1053/j.gastro.2014.03.050 · DOI · Paper page
  30. Pachkoria, 2008, Analysis of IL-10, IL-4 and TNF-alpha polymorphisms in drug-induced liver injury (DILI) and its outcome, J Hepatol, 49, 107, 10.1016/j.jhep.2008.03.017 · DOI
  31. Fernández-Castañer, 2008, An analysis of the causes, characteristics, and consequences of reexposure to a drug or compound responsible for a hepatotoxicity event, Rev Esp Enferm Dig, 100, 278
  32. Teschke, 2016, Drug, Herb, and Dietary Supplement Hepatotoxicity, Int J Mol Sci, 17, 1488, 10.3390/ijms17091488 · DOI
  33. Verma, 2007, Complementary and alternative medicine in hepatology: review of the evidence of efficacy, Clin Gastroenterol Hepatol, 5, 408, 10.1016/j.cgh.2006.10.014 · DOI
  34. García-Cortés, 2011, Causality assessment methods in drug induced liver injury: strengths and weaknesses, J Hepatol, 55, 683, 10.1016/j.jhep.2011.02.007 · DOI · Paper page

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Authors
Medina-Caliz, I., Garcia-Cortes, M., Gonzalez-Jimenez, A., Cabello, M. R., Robles-Diaz, M., Sanabria-Cabrera, J., Sanjuan-Jimenez, R., Ortega-Alonso, A., García-Muñoz, B., Moreno, I., Jimenez-Perez, M., Fernandez, M. C., Ginés, P., Prieto, M., Conde, I., Hallal, H., Soriano, G., Roman, E., Castiella, A., Blanco-Reina, E., Montes, M. R., Quiros-Cano, M., Martin-Reyes, F., Lucena, M. I., Andrade, R. J., Andrade, R., Lucena, M., Stephens, C., García-Cortés, M., Robles-Díaz, M., Medina-Cáliz, I., Sanabria, J., García-Muñoz, B., Alcántara, R., Moreno, I., Gonzalez-Jimenez, A., Ortega-Alonso, A., Sanjuán-Jiménez, R., Quirós, M., Martín-Reyes, F., Papineau, A., Jiménez-Pérez, M., González-Grande, R., Fernández, M., Peláez, G., Casado, M., González-Sánchez, M., Romero-Gómez, M., Calle-Sanz, R., Millán-Domínguez, R., Fombuena, B., Gallego, R., Rojas, L., Rojas, A., Ampuero, J., del Campo, J., Gil Gómez, A., Vilar, E., Castiella, A., Zapata, E., Zubiaurre, L., Navarro, J., Méndez-Sánchez, I., Chaves, A., Soriano, G., Guarner, C., Román, E., Hallal, H., García-Oltra, E., Titos-Arcos, J., Pérez-Martínez, A., Sánchez-Cobarro, C., Egea-Caparrós, J., Arenas, J., Gomez-Osua, M., Gómez-García, A., Esandi, F., Blanco, S., Martínez-Odriozola, P., Otazua, P., Salmerón, J., Gila, A., Quiles, R., González, J., Lorenzo, S., Prieto, M., Conde, I., Amiel, Berenguer, M., García-Eliz, M., Primo, J., Molés, Jr., Garayoa, A., Carrascosa, M., Gómez- Domínguez, E., Montané, E., Arellano, A., Barriocanal, A., Sanz, Y., Morillas, R., Sala, M., Masnou, H., Farré, M., Bruguera, M., Gines, P., Lens, S., García, J., Aldea-Perona, A., Hernández-Guerra, M., Moreno-San Fiel, M., Boada-Fernández del Campo, C., Tejedor, M., González-Ferrer, R., Fernández, C., Fernández-Gil, M., Montero, J., de la Mata, M., Fuentes-Olmo, J., Fernández-Bonilla, E., González-Gallego, J., Jorquera, F., Moreno, J., Martínez-Rodenas, P., Garrido, M., Rendón, P., Vergara, M., Sánchez Delgado, J., García Samaniego, J., Madejón, A., Cabriada, J., Crespo, J., Giráldez Gallego, A., Cuaresma, M., & Ruíz, R.
Affiliations
  • Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (ES)
  • Spanish Clinical Research Network (ES)
  • Hospital El Cruce (AR)
  • Complejo Hospitalario Torrecárdenas (ES)
  • Hospital Regional Universitario de Málaga (ES)
  • Hospital de Sant Pau (ES)
  • Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno (AR)
Corresponding author
  • Lucena, M. Isabel
  • Lucena, MI
ORCID
Venue
Clinical Gastroenterology and Hepatology
Publisher
Elsevier BV
Published
2018-09
Volume
16
Issue
9
Pages
1495-1502
ISSN
1542-3565 (ISSN-L)
DOI
10.1016/j.cgh.2017.12.051
OpenAlex
W2782039472
Cited by
111
References
3
Citations by year
2026: 10 · 2025: 7 · 2024: 11 · 2023: 8 · 2022: 11 · 2021: 16 · 2020: 11 · 2019: 27 · 2018: 9
FWCI
11.09
Type
journal article
Language
en
Open access
Licence
Locations
  • Clinical Gastroenterology and Hepatology (publishedVersion)
  • PubMed (publishedVersion)
  • Repositorio Institucional de la Universidad de Málaga (University of Málaga) (submittedVersion, cc-by-nc-nd)
Funders
  • Servicio Andaluz de Salud
  • Instituto de Salud Carlos III (CD20/00083, PI18/01804, PI18/00901, PI-0274-2016, PI-0285-2016)
  • European Regional Development Fund (PI18/01804, PI18-00901, PI-0285-2016, PI-0274-2016)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
  • Health Sciences › Medicine › Complementary and alternative medicine › Complementary and Alternative Medicine Studies
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Plant Toxicity and Pharmacological Properties
Keywords
drug-induced liver injury, herbal supplements, dietary supplements, hepatotoxicity, acute liver failure, anabolic steroids, jaundice, transaminases, re-exposure
MeSH terms
Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Child, Drugs, Chinese Herbal, Female, Humans, Male, Middle Aged, Risk Factors, Sex Factors, Spain, Dietary Supplements, Young Adult, Chemical and Drug Induced Liver Injury

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