Camilla Stephens1, Mercedes Robles-Diaz1, Inmaculada Medina-Caliz2, Miren Garcia-Cortes1, Aida Ortega-Alonso1, Judith Sanabria-Cabrera3, Andres Gonzalez-Jimenez2, Ismael Alvarez-Alvarez2, Mahmoud Slim2, Miguel Jimenez-Perez4, Rocio Gonzalez-Grande4, M Carmen Fernández5, Marta Casado5, German Soriano6, Eva Román7, Hacibe Hallal8, Manuel Romero-Gomez9, Agustin Castiella10, Isabel Conde11, Martin Prieto11, Jose Maria Moreno-Planas12, Alvaro Giraldez13, J Miguel Moreno-Sanfiel14, Neil Kaplowitz15, M Isabel Lucena16, Raúl J Andrade1. 1. UGC Aparato Digestivo and Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain. 2. UGC Aparato Digestivo and Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain. 3. UGC Aparato Digestivo and Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain; Platform ISCiii for Clinical Research and Clinical Trials UICEC- IBIMA, Málaga, Spain. 4. UGC Aparato Digestivo, Complejo Hospitalario Regional de Málaga, IBIMA, Málaga, Spain. 5. UGC Farmacia, Hospital Universitario Torrecárdenas, Almeria, Spain. 6. Servicio de Gastroenterología, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain. 7. Servicio de Gastroenterología, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain; Escola Universitària d'Infermeria EUI-Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain. 8. Servicio Aparato Digestivo, Hospital General Universitario J.M. Morales Meseguer, Murcia, Spain. 9. UGC Aparato Digestivo, SeLiver Group IBIS, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Sevilla, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain. 10. Servicio de Aparato Digestivo, Hospital Universitario de Donostia, San Sebastian, Spain. 11. Unidad de Hepatología, Servicio de Aparato Digestivo, Hospital Universitari i Politècnic La Fe, Valencia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain. 12. Servicio de Digestivo, Complejo Hospitalario Universitario de Albacete, Albacete, Spain. 13. Servicio de Aparato Digestivo. Hospital Virgen del Rocío, Sevilla, Spain. 14. Servicio de Aparato Digestivo. Hospital Universitario de Canarias, Tenerife, Spain. 15. University of Southern California Research Center for Liver Diseases, Keck School of Medicine, Los Angeles, California, USA. 16. UGC Aparato Digestivo and Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain; Platform ISCiii for Clinical Research and Clinical Trials UICEC- IBIMA, Málaga, Spain. Electronic address: lucena@uma.es.
Abstract
BACKGROUND & AIMS: Prospective drug-induced liver injury (DILI) registries are important sources of information on idiosyncratic DILI. We aimed to present a comprehensive analysis of 843 patients with DILI enrolled into the Spanish DILI Registry over a 20-year time period. METHODS: Cases were identified, diagnosed and followed prospectively. Clinical features, drug information and outcome data were collected. RESULTS: A total of 843 patients, with a mean age of 54 years (48% females), were enrolled up to 2018. Hepatocellular injury was associated with younger age (adjusted odds ratio [aOR] per year 0.983; 95% CI 0.974-0.991) and lower platelet count (aOR per unit 0.996; 95% CI 0.994-0.998). Anti-infectives were the most common causative drug class (40%). Liver-related mortality was more frequent in patients with hepatocellular damage aged ≥65 years (p = 0.0083) and in patients with underlying liver disease (p = 0.0221). Independent predictors of liver-related death/transplantation included nR-based hepatocellular injury, female sex, higher onset aspartate aminotransferase (AST) and bilirubin values. nR-based hepatocellular injury was not associated with 6-month overall mortality, for which comorbidity burden played a more important role. The prognostic capacity of Hy's law varied between causative agents. Empirical therapy (corticosteroids, ursodeoxycholic acid and MARS) was prescribed to 20% of patients. Drug-induced autoimmune hepatitis patients (26 cases) were mainly females (62%) with hepatocellular damage (92%), who more frequently received immunosuppressive therapy (58%). CONCLUSIONS: AST elevation at onset is a strong predictor of poor outcome and should be routinely assessed in DILI evaluation. Mortality is higher in older patients with hepatocellular damage and patients with underlying hepatic conditions. The Spanish DILI Registry is a valuable tool in the identification of causative drugs, clinical signatures and prognostic risk factors in DILI and can aid physicians in DILI characterisation and management. LAY SUMMARY: Clinical information on drug-induced liver injury (DILI) collected from enrolled patients in the Spanish DILI Registry can guide physicians in the decision-making process. We have found that older patients with hepatocellular type liver injury and patients with additional liver conditions are at a higher risk of mortality. The type of liver injury, patient sex and analytical values of aspartate aminotransferase and total bilirubin can also help predict clinical outcomes.
BACKGROUND & AIMS: Prospective drug-induced liver injury (DILI) registries are important sources of information on idiosyncratic DILI. We aimed to present a comprehensive analysis of 843 patients with DILI enrolled into the Spanish DILI Registry over a 20-year time period. METHODS: Cases were identified, diagnosed and followed prospectively. Clinical features, drug information and outcome data were collected. RESULTS: A total of 843 patients, with a mean age of 54 years (48% females), were enrolled up to 2018. Hepatocellular injury was associated with younger age (adjusted odds ratio [aOR] per year 0.983; 95% CI 0.974-0.991) and lower platelet count (aOR per unit 0.996; 95% CI 0.994-0.998). Anti-infectives were the most common causative drug class (40%). Liver-related mortality was more frequent in patients with hepatocellular damage aged ≥65 years (p = 0.0083) and in patients with underlying liver disease (p = 0.0221). Independent predictors of liver-related death/transplantation included nR-based hepatocellular injury, female sex, higher onset aspartate aminotransferase (AST) and bilirubin values. nR-based hepatocellular injury was not associated with 6-month overall mortality, for which comorbidity burden played a more important role. The prognostic capacity of Hy's law varied between causative agents. Empirical therapy (corticosteroids, ursodeoxycholic acid and MARS) was prescribed to 20% of patients. Drug-induced autoimmune hepatitis patients (26 cases) were mainly females (62%) with hepatocellular damage (92%), who more frequently received immunosuppressive therapy (58%). CONCLUSIONS: AST elevation at onset is a strong predictor of poor outcome and should be routinely assessed in DILI evaluation. Mortality is higher in older patients with hepatocellular damage and patients with underlying hepatic conditions. The Spanish DILI Registry is a valuable tool in the identification of causative drugs, clinical signatures and prognostic risk factors in DILI and can aid physicians in DILI characterisation and management. LAY SUMMARY: Clinical information on drug-induced liver injury (DILI) collected from enrolled patients in the Spanish DILI Registry can guide physicians in the decision-making process. We have found that older patients with hepatocellular type liver injury and patients with additional liver conditions are at a higher risk of mortality. The type of liver injury, patient sex and analytical values of aspartate aminotransferase and total bilirubin can also help predict clinical outcomes.
Authors: Antonio Segovia-Zafra; Daniel E Di Zeo-Sánchez; Carlos López-Gómez; Zeus Pérez-Valdés; Eduardo García-Fuentes; Raúl J Andrade; M Isabel Lucena; Marina Villanueva-Paz Journal: Acta Pharm Sin B Date: 2021-11-18 Impact factor: 11.413
Authors: Paul H Hayashi; M Isabel Lucena; Robert J Fontana; Einar S Bjornsson; Guruprasad P Aithal; Huiman Barnhart; Andres Gonzalez-Jimenez; Qinghong Yang; Jiezhun Gu; Raul J Andrade; Jay H Hoofnagle Journal: Hepatology Date: 2022-03-22 Impact factor: 17.298