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Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry

2021; Elsevier BV; Volume: 75; Issue: 1 Linguagem: Inglês

10.1016/j.jhep.2021.01.029

1600-0641

Camilla Stephens, Mercedes Robles‐Díaz, Inmaculada Medina‐Cáliz, Miren García‐Cortés, Aida Ortega‐Alonso, Judith Sanabria‐Cabrera, A. González-Jiménez, Ismael Álvarez‐Álvarez, Mahmoud Slim, Miguel Jiménez‐Pérez, Rocío González‐Grande, M. Carmen Fernández, Marta Casado, Germán Soriano, Eva Román, Hacibe Hallal, Manuel Romero‐Gómez, Agustín Castiella, Isabel Conde, M. Prieto, J.M. Moreno Planas, Álvaro Giráldez Gallego, J. Miguel Moreno-Sanfiel, Neil Kaplowitz, M. Isabel Lucena, Raúl J. Andrade, Raúl J. Andrade, M. Isabel Lucena, Camilla Stephens, M. García Cortés, Mercedes Robles‐Díaz, Aida Ortega‐Alonso, José Pinazo, B. García Muñoz, R. Alcántara, Arielle G. Hernandez, María Dolores García Escaño, E. del Campo, Inmaculada Medina‐Cáliz, Judith Sanabria‐Cabrera, A. González-Jiménez, Rocío Sanjuán‐Jiménez, Abril Rosario Leal Cueto, Ismael Álvarez‐Álvarez, Elvira Bonilla‐Toyos, D. Di Zeo, Hao Niu, Mercè Villanueva, Alyssa M. Papineau, Miguel Jiménez Pérez, Rocío González Grande, S. López Ortega, Ignacio Obando, Alberto Ocaña, Pierina Zevallos Palomino, M. Carmen Fernández, Gloria Isabel Carvajal Peláez, A. Porcel, Marta Casado, Marta Sánchez‐Soto, Manuel Romero‐Gómez, Raquel Millan‐Domínguez, Blanca Fombuena, R. Gallego, Javier Ampuero, J.A. Del Campo, R. Calle-Sanz, Liliana Rojas, Ángela Rojas, Antonio Gil‐Gómez, Eduardo Vilar, Germán Soriano, Carlos Guarner, Eva Román, M.A. Quijada Manuitt, Rosa M. Antonijoan Arbos, Josué Delgado, Montserrat Gómez, Hacibe Hallal, E. García Oltra, J.C. Titos Arcos, A. Pérez Martínez, C. Sánchez Cobarro, J. Caparrós, Agustín Castiella, Eva Zapata, Juan Arenas, Alvaro Garcia, F.J. Esandi, Sonia Blanco, Pedro Martínez Odriozola, Javier Crespo, Paula Iruzubieta, Joaquín Cabezas, Álvaro Giráldez Gallego, E. del P. Rodríguez Seguel, M. Cuaresma, Javier González‐Gallego, Francisco Jorquera, S. Sánchez Campos, Pedro Otazua, ANTÓN GÓMEZ, Javier Salmerón, A. Gómez Gila, R. Quiles, J. M. González, Sandra Lorenzo, M. Prieto, Imri Amiel, Marina Berenguer, María García‐Eliz, J Primo, J.R. Molés, Ana Garayoa, Miguel F. Carrascosa, Eva Dominguez, Lourdes Cuevas, M. Llobet Farré, Eva Montané, Ana María Barriocanal, Ana Lucía Arellano, Yolanda Sanz, R Morillas, Margarita Sala, Helena Masnou Ridaura, Miguel Bruguera, Pere Ginés, Sabela Lens, J C García, Zoe Mariñó, Marta Guerra, Juan M. Moreno Sanfiel, Columbus Campo, María Teresa Tejedor, Ruth González Ferrer, Carmen Muñoz Fernández, Montserrat Gil, JL Montero, Manuel de la Mata, Javier Fuentes Olmo, Elvira Bonilla‐Toyos, J.M. Moreno Planas, P. Martínez-Rodenas, Marı́a J. Garrido, Clara Oliva, Paloma Rendón, Javier García‐Samaniego, Antonio Madejón, José Luís Calleja, José Luis Martínez Porras, JL Cabriada, J.M. Pérez-Moreno, Carmen Lara,

Drug Transport and Resistance Mechanisms

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.