Gastroenterology
Volume 129, Issue 2 , Pages 512-521 , August 2005

Drug-Induced Liver Injury: An Analysis of 461 Incidences Submitted to the Spanish Registry Over a 10-Year Period

  • Raúl J. Andrade

      Affiliations

    • Unidad de Hepatología y Grupo de Estudio para las Hepatopatías Asociadas a Medicamentos, Coordinating Centre, Hospital Universitario Virgen de la Victoria, Facultad de Medicina, Campus Universitario de Teatinos s/n, Málaga, Spain
    • Corresponding Author InformationAddress requests for reprints to: Raúl J Andrade, MD, Prof, Unidad de Hepatología, Departamento de Medicina, Facultad de Medicina, Campus de Teatinos s/n, 29071-Málaga, Spain.fax: (34) 952 131511
  • ,
  • M. Isabel Lucena

      Affiliations

    • Servicio de Farmacología Clínica, Grupo de Estudio para las Hepatopatías Asociadas a Medicamentos, Coordinating Centre, Hospital Universitario Virgen de la Victoria, Facultad de Medicina, Campus Universitario de Teatinos s/n, Málaga, Spain
  • ,
  • M. Carmen Fernández

      Affiliations

    • Unidad de Farmacología Clínica y Servicio de Aparato Digestivo, Hospital Torrecárdenas, Almeria, Spain
  • ,
  • Gloria Pelaez

      Affiliations

    • Unidad de Farmacología Clínica y Servicio de Aparato Digestivo, Hospital Torrecárdenas, Almeria, Spain
  • ,
  • Ketevan Pachkoria

      Affiliations

    • Servicio de Farmacología Clínica, Grupo de Estudio para las Hepatopatías Asociadas a Medicamentos, Coordinating Centre, Hospital Universitario Virgen de la Victoria, Facultad de Medicina, Campus Universitario de Teatinos s/n, Málaga, Spain
  • ,
  • Elena García-Ruiz

      Affiliations

    • Unidad de Hepatología y Grupo de Estudio para las Hepatopatías Asociadas a Medicamentos, Coordinating Centre, Hospital Universitario Virgen de la Victoria, Facultad de Medicina, Campus Universitario de Teatinos s/n, Málaga, Spain
  • ,
  • Beatriz García-Muñoz

      Affiliations

    • Unidad de Hepatología y Grupo de Estudio para las Hepatopatías Asociadas a Medicamentos, Coordinating Centre, Hospital Universitario Virgen de la Victoria, Facultad de Medicina, Campus Universitario de Teatinos s/n, Málaga, Spain
  • ,
  • Rocio González-Grande

      Affiliations

    • Unidad de Hepatología y Grupo de Estudio para las Hepatopatías Asociadas a Medicamentos, Coordinating Centre, Hospital Universitario Virgen de la Victoria, Facultad de Medicina, Campus Universitario de Teatinos s/n, Málaga, Spain
  • ,
  • Angeles Pizarro

      Affiliations

    • Unidad de Hepatología y Grupo de Estudio para las Hepatopatías Asociadas a Medicamentos, Coordinating Centre, Hospital Universitario Virgen de la Victoria, Facultad de Medicina, Campus Universitario de Teatinos s/n, Málaga, Spain
  • ,
  • José Antonio Durán

      Affiliations

    • Unidad de Farmacología Clínica y Servicio de Aparato Digestivo, Hospital Virgen de la Macarena, Sevilla, Spain
  • ,
  • Manuel Jiménez

      Affiliations

    • Unidad de Farmacología Clínica y Servicio de Aparato Digestivo, Hospital Virgen de la Macarena, Sevilla, Spain
  • ,
  • Luis Rodrigo

      Affiliations

    • Servicio de Aparato Digestivo, Hospital Central de Asturias, Oviedo, Spain
  • ,
  • Manuel Romero-Gomez

      Affiliations

    • Unidad de Hepatología, Hospital Universitario de Valme, Sevilla, Spain
  • ,
  • José María Navarro

      Affiliations

    • Servicio de Aparato Digestivo, Hospital Costa del Sol, Málaga, Spain
  • ,
  • Ramón Planas

      Affiliations

    • Servicios de Farmacología Clínica y Servicio de Aparato Digestivo, Hospital Germans Trias i Puyol, Barcelona, Spain
  • ,
  • Joan Costa

      Affiliations

    • Servicios de Farmacología Clínica y Servicio de Aparato Digestivo, Hospital Germans Trias i Puyol, Barcelona, Spain
  • ,
  • Africa Borras

      Affiliations

    • Servicios de Farmacología Clínica y Servicio de Aparato Digestivo, Hospital Germans Trias i Puyol, Barcelona, Spain
  • ,
  • Aina Soler

      Affiliations

    • Servicios de Farmacología Clínica y Servicio de Aparato Digestivo, Hospital Germans Trias i Puyol, Barcelona, Spain
  • ,
  • Javier Salmerón

      Affiliations

    • Servicio de Aparato Digestivo, Hospital Universitario San Cecilio, Granada, Spain
  • ,
  • Rafael Martin-Vivaldi

      Affiliations

    • Servicio de Aparato Digestivo, Hospital Virgen de las Nieves, Granada, Spain
  • ,
  • Spanish Group for the Study of Drug-Induced Liver Disease

Received 2 December 2004 ,Accepted 20 April 2005.

References 

  1. Bakke OM , Manocchia M , De Abajo F , Kaitin KI , Lasagna L . Drug safety discontinuations in the United Kingdom, the United States, and Spain from 1974 through 1993 (a regulatory perspective) . Clin Pharmacol Ther . 1995;58:108–117
  2. Larrey D . Epidemiology and individual susceptibility to adverse drug reactions affecting the liver . Semin Liver Dis . 2002;22:145–155
  3. Sgro C, Clinard F, Ouazir K, Chanay H, Allard C, Guilleminet C, et al. Incidence of drug-induced hepatic injuries (a French population-based study) . Hepatology . 2002;36:451–455
  4. Aithal GP , Rawlins MD , Day CP . Accuracy of hepatic adverse drug reaction reporting in one English health region . BMJ . 1999;319:1541
  5. Zimmerman HJ . Hepatotoxicity. The adverse effects of drugs and other chemicals on the liver. 2nd ed . Philadelphia: Lippincott Williams & Wilkins; 1999;
  6. Andrade RJ, Lucena MI, Martín-Vivaldi R, Fernandez MC, Nogueras F, Pelaez G, et al. Acute liver injury associated with the use of ebrotidine, a new H2- receptor antagonist . J Hepatol . 1999;31:641–646
  7. Andrade RJ , Lucena MI , Alcantara R , Fraile JM . Bentazepam-associated chronic liver disease . Lancet . 1994;343:860
  8. Andrade RJ , Lucena MI , Rodriguez-Mendizabal M . Hepatic injury caused by acarbose . Ann Intern Med . 1996;124:931
  9. Cahalan D . Quantifying alcohol consumption (patterns and problems) . Circulation . 1981;64:7–14
  10. Benichou C . Criteria of drug-induced liver disorders. Report of an international consensus meeting . J Hepatol . 1990;11:272–276
  11. World Health Organization Collaborating Center for drugs statistics methodology . Anatomical Therapeutic Chemical (ATC) classification index including defined daily dose (DDDs) for plain substances . Oslo: World Health Organization Collaborating Center for drugs statistics methodology; 2002;
  12. Kaplowitz N . Causality assessment versus guilt-by-association in drug hepatotoxicity . Hepatology . 2001;33:308–310
  13. 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;46:1323–1330
  14. Lucena MI , Camargo R , Andrade RJ , Perez-Sanchez C , Sanchez De La Cuesta F . Comparison of two clinical scales for causality assessment in hepatotoxicity . Hepatology . 2001;33:123–130
  15. Arnaiz JA , Carne X , Riba N , Codina C , Ribas J , Trilla A . The use of evidence in pharmacovigilance. Case reports as the reference source for drug withdrawals . Eur J Clin Pharmacol . 2001;57:89–91
  16. Hoofnagle JH . Drug-induced liver injury network (DILIN) . Hepatology . 2004;40:773
  17. Peire MA , Lucena MI , Ruiz-Extremera A , Jara P , Romero-Gonzalez J , Andrade RJ . Toxicidad hepatica por fármacos. Donde estamos y hacia donde caminamos . An Esp Pediatr . 2002;56:434–442
  18. Ibáñez L , Pérez E , Vidal X , Laporte JR  Grup d’Estudi Multicentric d’Hepatotoxicitat Aguda de Barcelona (GEMHAB) . Prospective surveillance of acute serious liver disease unrelated to infectious, obstructive, or metabolic diseases (epidemiological and clinical features, and exposure to drugs) . J Hepatol . 2002;37:592–600
  19. Friis H , Andreasen PB . Drug-induced hepatic injury (an analysis of 1100 cases reported to the Danish Committee on Adverse Drug Reactions between 1978 and 1987) . J Intern Med . 1992;232:133–138
  20. Almdal TP , Sorensen TI  The Danish Association for the Study of the Liver . Incidence of parenchymal liver disease in Denmark, 1981 to 1985 (analysis of hospitalization registry data) . Hepatology . 1991;13:650–655
  21. Ostapowicz G, Fontana RJ, Schiodt FV, Larson A, Davern TJ, Han SH, et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States . Ann Intern Med . 2002;137:947–957
  22. 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;10:1018–1023
  23. Garcia Rodriguez LA , Williams R , Derby LE , Dean AD , Jick H . Acute liver injury associated with nonsteroidal anti-inflammatory drugs and the role of risk factors . Arch Intern Med . 1994;154:311–316
  24. de Abajo FJ , Montero D , Madurga M , Garcia Rodriguez LA . Acute and clinically relevant drug-induced liver injury (a population based case-control study) . Br J Clin Pharmacol . 2004;58:71–80
  25. Pham BN, Bernuau J, Durand F, Sauvanet A, Degott C, Prin L, et al. Eotaxin expression and eosinophil infiltrate in the liver of patients with drug-induced liver disease . J Hepatol . 2001;34:537–547
  26. Larrey D . Drug-induced liver disease . J Hepatol . 2000;32:77–88
  27. Maria VA , Victorino RM . Immunological investigation in hepatic drug reactions . Clin Exp Allergy . 1998;28:71–77
  28. Andrade RJ , Lucena MI . Drug-induced hepatotoxicity . N Engl J Med . 2003;349:1974–1976
  29. Andrade RJ, Lucena MI, Alonso A, Garcia-Cortes M, Garcia-Ruiz E, Benitez R, et al. HLA class II genotype influences the type of liver injury in drug-induced idiosyncratic liver disease . Hepatology . 2004;39:1603–1612
  30. Aithal PG , Day CP . The natural history of histologically proved drug induced liver disease . Gut . 1999;44:731–735
  31. Lopez-Torres E, Lucena MI, Andrade RJ, Garcia-Ruiz E, Fernandez MC, Pelaez G, et al. Tetrabamate-induced hepatotoxicity. Report of seven cases and literature review . Gastroenterol Hepatol . 2002;25:589–593
  32. Lucena MI , Andrade RJ , Gomez-Outes A , Rubio M , Cabello MR . Acute liver failure after treatment with nefazodone . Dig Dis Sci . 1999;44:2577–2579

 Supported in part by a research grant from the Agencia Española del Medicamento.

PII: S0016-5085(05)00876-0

doi: 10.1053/j.gastro.2005.05.006

Gastroenterology
Volume 129, Issue 2 , Pages 512-521 , August 2005