Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry
Authors: Camilla Stephens, Mercedes Robles-Diaz, Inmaculada Medina-Caliz, Miren Garcia-Cortes, Aida Ortega-Alonso, Judith Sanabria-Cabrera, Andres Gonzalez-Jimenez, Ismael Alvarez-Alvarez, Mahmoud Slim, Miguel Jimenez-Perez, Rocio Gonzalez-Grande, M. Carmen Fernández, Marta Casado, German Soriano, Eva Román, Hacibe Hallal, Manuel Romero-Gomez, Agustin Castiella, Isabel Conde, Martin Prieto, Jose Maria Moreno-Planas, Alvaro Giraldez, J. Miguel Moreno-Sanfiel, Neil Kaplowitz, M. Isabel Lucena, Raúl J. Andrade, R.J. Andrade, M.I. Lucena, C. Stephens, M. García Cortés, M. Robles-Díaz, A. Ortega-Alonso, J. Pinazo, B. García Muñoz, R. Alcántara, A. Hernández, M.D. García Escaño, E. del Campo, I. Medina-Cáliz, J. Sanabria-Cabrera, A. González-Jiménez, R. Sanjuán-Jiménez, A. Cueto, I. Álvarez-Álvarez, E. Bonilla, D. Di Zeo, H. Niu, M. Villanueva, A. Papineau, M. Jiménez Pérez, R. González Grande, S. López Ortega, I. Santaella, A. Ocaña, P. Palomino, M.C. Fernández, G. Peláez, A. Porcel, M. Casado, M. González Sánchez, M. Romero-Gómez, R. Millán-Domínguez, B. Fombuena, R. Gallego, J. Ampuero, J.A. del Campo, R. Calle-Sanz, L. Rojas, A. Rojas, A. Gil Gómez, E. Vilar, G. Soriano, C. Guarner, E.M. Román, M.A. Quijada Manuitt, R.M. Antonijoan Arbos, J. Sánchez Delgado, M. Vergara Gómez, H. Hallal, E. García Oltra, J.C. Titos Arcos, A. Pérez Martínez, C. Sánchez Cobarro, J.M. Egea Caparrós, A. Castiella, E. Zapata, J. Arenas, A. Gómez García, F.J. Esandi, S. Blanco, P. Martínez Odriozola, J. Crespo, P. Iruzubieta, J. Cabezas, A. Giráldez Gallego, E. del P. Rodríguez Seguel, M. Cuaresma, J. González Gallego, F. Jorquera, S. Sánchez Campos, P. Otazua, A. de Juan Gómez, J. Salmerón, A. Gila, R. Quiles, J.M. González, S. Lorenzo, M. Prieto, I. Conde Amiel, M. Berenguer, M. García-Eliz, J. Primo, J.R. Molés, A. Garayoa, M. Carrascosa, E. Gómez Domínguez, L. Cuevas, M. Farré, E. Montané, A.M. Barriocanal, A.L. Arellano, Y. Sanz, R.M. Morillas, M. Sala, H. Masnou Ridaura, M. Bruguera, P. Gines, S. Lens, J.C. García, Z. Mariño, M. Hernández Guerra, J.M. Moreno Sanfiel, C. Boada Fernández del Campo, M. Tejedor, R. González Ferrer, C. Fernández, M. Fernández Gil, J.L. Montero, M. de la Mata, J. Fuentes Olmo, E.M. Fernández Bonilla, J.M. Moreno, P. Martínez-Rodenas, M. Garrido, C. Oliva, P. Rendón, J. García Samaniego, A. Madejón, J.L. Calleja, J.L. Martínez Porras, J.L. Cabriada, J.M. Pérez-Moreno, C. Lara
Journal: Journal of Hepatology (2021)

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.Cases were identified, diagnosed and followed prospectively. Clinical features, drug information and outcome data were collected.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%).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.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.