Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry
Por:
Stephens, C, Robles-Diaz, M, Medina-Caliz, I, Garcia-Cortes, M, Ortega-Alonso, A, Sanabria-Cabrera, J, Gonzalez-Jimenez, A, Alvarez-Alvarez, I, Slim, M, Jimenez-Perez, M, Gonzalez-Grande, R, Fernandez, MC, Casado, M, Soriano, G, Roman, E, Hallal, H, Romero-Gomez, M, Castiella, A, Conde, I, Prieto, M, Moreno-Planas, JM, Giraldez, A, Moreno-Sanfiel, JM, Kaplowitz, N, Lucena, MI, Andrade, RJ, Participating Clinical Ctr
Publicada:
1 jul 2021
Ahead of Print:
1 jun 2021
Resumen:
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. (C) 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Filiaciones:
Stephens, C:
Univ Malaga, Hosp Univ Virgen de la Victoria, Inst Invest Biomed Malaga IBIMA, UGC Aparato Digest, Malaga, Spain
Univ Malaga, Hosp Univ Virgen de la Victoria, Inst Invest Biomed Malaga IBIMA, Serv Farmacol Clin, Malaga, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Robles-Diaz, M:
Univ Malaga, Hosp Univ Virgen de la Victoria, Inst Invest Biomed Malaga IBIMA, UGC Aparato Digest, Malaga, Spain
Univ Malaga, Hosp Univ Virgen de la Victoria, Inst Invest Biomed Malaga IBIMA, Serv Farmacol Clin, Malaga, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Medina-Caliz, I:
Univ Malaga, Hosp Univ Virgen de la Victoria, Inst Invest Biomed Malaga IBIMA, UGC Aparato Digest, Malaga, Spain
Univ Malaga, Hosp Univ Virgen de la Victoria, Inst Invest Biomed Malaga IBIMA, Serv Farmacol Clin, Malaga, Spain
Garcia-Cortes, M:
Univ Malaga, Hosp Univ Virgen de la Victoria, Inst Invest Biomed Malaga IBIMA, UGC Aparato Digest, Malaga, Spain
Univ Malaga, Hosp Univ Virgen de la Victoria, Inst Invest Biomed Malaga IBIMA, Serv Farmacol Clin, Malaga, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Ortega-Alonso, A:
Univ Malaga, Hosp Univ Virgen de la Victoria, Inst Invest Biomed Malaga IBIMA, UGC Aparato Digest, Malaga, Spain
Univ Malaga, Hosp Univ Virgen de la Victoria, Inst Invest Biomed Malaga IBIMA, Serv Farmacol Clin, Malaga, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Sanabria-Cabrera, J:
Univ Malaga, Hosp Univ Virgen de la Victoria, Inst Invest Biomed Malaga IBIMA, UGC Aparato Digest, Malaga, Spain
Univ Malaga, Hosp Univ Virgen de la Victoria, Inst Invest Biomed Malaga IBIMA, Serv Farmacol Clin, Malaga, Spain
Platform ISCiii Clin Res & Clin Trials UICEC IBIM, Malaga, Spain
Gonzalez-Jimenez, A:
Univ Malaga, Hosp Univ Virgen de la Victoria, Inst Invest Biomed Malaga IBIMA, UGC Aparato Digest, Malaga, Spain
Univ Malaga, Hosp Univ Virgen de la Victoria, Inst Invest Biomed Malaga IBIMA, Serv Farmacol Clin, Malaga, Spain
Alvarez-Alvarez, I:
Univ Malaga, Hosp Univ Virgen de la Victoria, Inst Invest Biomed Malaga IBIMA, UGC Aparato Digest, Malaga, Spain
Univ Malaga, Hosp Univ Virgen de la Victoria, Inst Invest Biomed Malaga IBIMA, Serv Farmacol Clin, Malaga, Spain
Slim, M:
Univ Malaga, Hosp Univ Virgen de la Victoria, Inst Invest Biomed Malaga IBIMA, UGC Aparato Digest, Malaga, Spain
Univ Malaga, Hosp Univ Virgen de la Victoria, Inst Invest Biomed Malaga IBIMA, Serv Farmacol Clin, Malaga, Spain
Jimenez-Perez, M:
Complejo Hosp Reg Malaga, IBIMA, UGC Aparato Digest, Malaga, Spain
Gonzalez-Grande, R:
Complejo Hosp Reg Malaga, IBIMA, UGC Aparato Digest, Malaga, Spain
Fernandez, MC:
Hosp Univ Torrecardenas, UGC Farm, Almeria, Spain
Casado, M:
Hosp Univ Torrecardenas, UGC Farm, Almeria, Spain
Soriano, G:
Univ Autonoma Barcelona, Serv Gastroenterol, Hosp Santa Creu & St Pau, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Roman, E:
Univ Autonoma Barcelona, Serv Gastroenterol, Hosp Santa Creu & St Pau, Barcelona, Spain
Univ Autonoma Barcelona, Escola Univ Infermeria EUI St Pau, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Hallal, H:
Hosp Gen Univ JM Morales Meseguer, Serv Aparato Digest, Murcia, Spain
Romero-Gomez, M:
Univ Seville, Hosp Univ Virgen del Rocio, SeLiver Grp IBIS, UGC Aparato Digest, Seville, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Castiella, A:
Hosp Univ Donostia, Serv Aparato Digest, San Sebastian, Spain
Conde, I:
Hosp Univ & Politecn La Fe, Serv Aparato Digest, Unidad Hepatol, Valencia, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Prieto, M:
Hosp Univ & Politecn La Fe, Serv Aparato Digest, Unidad Hepatol, Valencia, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Moreno-Planas, JM:
Complejo Hosp Univ Albacete, Serv Digest, Albacete, Spain
Giraldez, A:
Hosp Virgen del Rocio, Serv Aparato Digest, Seville, Spain
Moreno-Sanfiel, JM:
Hosp Univ Canarias, Serv Aparato Digest, Tenerife, Spain
Kaplowitz, N:
Univ Southern Calif, Keck Sch Med, Res Ctr Liver Dis, Los Angeles, CA 90007 USA
Lucena, MI:
Univ Malaga, Hosp Univ Virgen de la Victoria, Inst Invest Biomed Malaga IBIMA, UGC Aparato Digest, Malaga, Spain
Univ Malaga, Hosp Univ Virgen de la Victoria, Inst Invest Biomed Malaga IBIMA, Serv Farmacol Clin, Malaga, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
Platform ISCiii Clin Res & Clin Trials UICEC IBIM, Malaga, Spain
Andrade, RJ:
Univ Malaga, Hosp Univ Virgen de la Victoria, Inst Invest Biomed Malaga IBIMA, UGC Aparato Digest, Malaga, Spain
Univ Malaga, Hosp Univ Virgen de la Victoria, Inst Invest Biomed Malaga IBIMA, Serv Farmacol Clin, Malaga, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain
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