The team of researchers leading this proposal also belongs to the Centro de Investigación Biomédica en Red - Enfermedades Hepáticas y Digestivas (CIBERehd), attached to the Instituto de Salud Carlos III.
Researchers from the Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina (IBIMA Plataforma BIONAND), the Hospital Universitario Virgen de la Victoria and the Centro de Investigación Biomédica en Red - Enfermedades Hepáticas y Digestivas (CIBERehd), part of the Instituto de Salud Carlos III, together with other international experts, have carried out a comprehensive analysis to address one of the biggest challenges in drug development, the early identification of drug-induced hepatotoxicity (DILI).
Las colaboraciones internacionales son clave para lograr impacto en la investigación traslacional, y los resultados de este esfuerzo colaborativo han llevado a la publicación de los resultados publicados en la revista ‘Journal of Hepatology’
Liver toxicity (DILI) is a complex and unpredictable event that can be caused by drugs as well as herbal or dietary supplements. Identifying DILI in preclinical stages of drug development remains a significant challenge for the pharmaceutical industry. To address this issue, the researchers conducted a systematic review of compounds used in evaluations of DILI in preclinical drug development. in vitro DILI in order to establish a list of positive (clearly hepatotoxic) control drugs and negative (without evidence of liver toxicity) for the validation of models in vitro of drug-induced hepatotoxicity.
The study, which was conducted according to the 2020 PRISMA guidelines, examined a wide range of original research articles focusing on drug-induced hepatotoxicity that used models of drug-induced hepatotoxicity. in vitro human subjects. Of the nearly 3,000 studies reviewed, 51 met the inclusion criteria, with 30 considered unrestrictedly reliable.
One of the main findings of the study was the lack of agreement among the researchers on the control compounds used in the evaluation. in vitro de la hepatotoxicidad inducida por fármacos. Sin embargo, tras un análisis exhaustivo de los datos clínicos y experimentales, junto con la colaboración del comité de expertos de la red ProEuroDILI Network, se propuso una lista final de 10 fármacos positivos y negativos para validar los modelos ‘in vitro’, con el objetivo de mejorar los regímenes de pruebas de seguridad preclínicas de medicamentos.
The impact and potential implications of this study are significant. The ability to predict human toxicity in the preclinical drug development process is crucial, and the new models in vitro with human samples play an increasingly important role in this regard. By establishing a consensus list of control drugs, this study provides a scientifically justified framework for improving the consistency of preclinical testing, an important challenge in the early identification of the risk of developing hepatotoxicity.
These findings are of utmost importance to all stakeholders involved in drug development, and can guide researchers in assessing safety profiles of new drugs, as well as inform regulatory agencies on possible improvements in regulatory guidelines, ensuring a more systematic and efficient approach to drug safety assessment.
The objectives set for this study would not have been possible without the joint effort of researchers belonging to several groups of the Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas - CIBEREHD (Raúl J. Andrade, M. Isabel Lucena, Antonio Segovia-Zafra, Marina Villanueva-Paz, Ismael Álvarez-Álvarez (CB07/04/2008), Javier Cubero, Universidad Complutense de Madrid (CB06/04/0082) and José C Fernández-Checa, Instituto de Investigaciones Biomédicas de Barcelona (CB06/04/0035)), as well as leading European researchers from the University of Lisbon (Portugal), the University of Ljubljana (Slovenia), and the University of Edinburgh (UK), under the COST action ProEuroDILINet consortium ( Translated with www.DeepL.com/Translator (free version)https://proeurodilinet.eu/), EASL DHILI Consortium (https://easldhiliconsortium.eu/) y Halt-RONIN (UKRI-Horizon Europe) https://halt-ronin.com/.
ARTICLE REFERENCE
Segovia-Zafra A, Villanueva-Paz M, Serras AS, Matilla-Cabello G, Bodoque-García A, Di Zeo-Sánchez D, Niu H, Álvarez-Álvarez I, Sanz-Villanueva L, Godec S, Milisav I, Bagnaninchi P, Andrade RJ, Lucena MI*, Fernández-Checa JC*, Cubero FJ, Miranda JP, Nelson LJ. Control Compounds for Preclinical Drug-Induced Liver Injury Assessment: Consensus-driven systematic review by the ProEuroDILI Network.
J Hepatol. 2024 May 2:S0168-8278(24)00325-8. doi: 10.1016/j.jhep.2024.04.026
Raúl J. Andrade Bellido, es Investigador Responsable del grupo consolidado ‘Hepatogastroenterología, Farmacología y Terapéutica Clínica Traslacional’ de IBIMA Plataforma BIONAND, Catedrático y Director del Departamento de Medicina en la Facultad de Medicina de la Universidad de Málaga, Jefe de Servicio Aparato Digestivo del Hospital Universitario Virgen de la Victoria en Málaga. Además, es el Responsable del Grupo Español de Hepatopatias asociadas a medicamentos (Spanish DILI Registry), el Coordinador de la Red Ibero-Americana de Hepatopatías asociadas a medicamentos (SLATINDILI) y también del Registro europeo de Hepatopatías asociadas a Medicamentos (Pro-Euro DILI Registry). Chair de la COST Action CA17112 – Prospective European Drug-Induced Liver Injury Network (PRO-EURO DILI NET) y del EASL DHILI Consortium. Horizonte2020. Framework Programme (European Union).
