Idiosyncratic drug-induced liver injury(iDILI) encompasses the unexpected harms that prescription and non-prescription drugs,herbal and dietary supplements can cause to the liver.iDILI remains a major public health pr...Idiosyncratic drug-induced liver injury(iDILI) encompasses the unexpected harms that prescription and non-prescription drugs,herbal and dietary supplements can cause to the liver.iDILI remains a major public health problem and a major cause of drug attrition.Given the lack of biomarkers for iDILI prediction,diagnosis and prognosis,searching new models to predict and study mechanisms of iDILI is necessary.One of the major limitations of iDILI preclinical assessment has been the lack of correlation between the markers of hepatotoxicity in animal toxicological studies and clinically significant iDILI.Thus,major advances in the understanding of iDILI susceptibility and pathogenesis have come from the study of well-phenotyped iDILI patients.However,there are many gaps for explaining all the complexity of iDILI susceptibility and mechanisms.Therefore,there is a need to optimize preclinical human in vitro models to reduce the risk of iDILI during drug development.Here,the current experimental models and the future directions in iDILI modelling are thoroughly discussed,focusing on the human cellular models available to study the pathophysiological mechanisms of the disease and the most used in vivo animal iDILI models.We also comment about in silico approaches and the increasing relevance of patient-derived cellular models.展开更多
Introduction Autoimmune diseases result from a breach of immunological self-tolerance and tissue damage by autoreactive T lymphocytes.Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection is characteriz...Introduction Autoimmune diseases result from a breach of immunological self-tolerance and tissue damage by autoreactive T lymphocytes.Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection is characterized by an inflammatory dysregulation that has been associated with the development of autoimmune processes[1].展开更多
基金supported by grants of Instituto de Salud Carlos Ⅲ cofounded by Fondo Europeo de Desarrollo Regional-FEDER (contract numbers: PI18/01804, PI19-00883, PT20/00127,UMA18-FEDERJA-194, PY18-3364, Spain)Consejería de Salud de Andalucía cofounded by FEDER (contract number: PEMP-0127-2020, Spain)+1 种基金SCReN and CIBERehd are funded by ISCⅢ (Spain)based upon work from COST Action “CA17112d Prospective European Drug-Induced Liver Injury Network” supported by COST (European Cooperation in Science and Technology)。
文摘Idiosyncratic drug-induced liver injury(iDILI) encompasses the unexpected harms that prescription and non-prescription drugs,herbal and dietary supplements can cause to the liver.iDILI remains a major public health problem and a major cause of drug attrition.Given the lack of biomarkers for iDILI prediction,diagnosis and prognosis,searching new models to predict and study mechanisms of iDILI is necessary.One of the major limitations of iDILI preclinical assessment has been the lack of correlation between the markers of hepatotoxicity in animal toxicological studies and clinically significant iDILI.Thus,major advances in the understanding of iDILI susceptibility and pathogenesis have come from the study of well-phenotyped iDILI patients.However,there are many gaps for explaining all the complexity of iDILI susceptibility and mechanisms.Therefore,there is a need to optimize preclinical human in vitro models to reduce the risk of iDILI during drug development.Here,the current experimental models and the future directions in iDILI modelling are thoroughly discussed,focusing on the human cellular models available to study the pathophysiological mechanisms of the disease and the most used in vivo animal iDILI models.We also comment about in silico approaches and the increasing relevance of patient-derived cellular models.
基金Instituto de Investigacion Biom-edica de Malaga-IBIMA,Hospital Universitario Virgen de la Victoria,Universidad de Malaga,Malaga,Spain,Centro de Investigacion Biomedica en Red de Enfermedades Hepa ticas y Digestivas(CIBERehd),Madrid,SpainGrants of Instituto de Salud CarlosⅢcofounded by Fondo Europeo de Desarrollo Regional-FEDER[contract numbers:PI18/00901,UMA18-FEDERJA-193],COST ACTION CA17112-Prospective European Drug-Induced Liver Injury Network and IMI2-Translational Safety Biomarker Pipeline(TransBioLine Horizonte 2020)CM21/00074(Rio Hortega contract:J.M.P.B.).
文摘Introduction Autoimmune diseases result from a breach of immunological self-tolerance and tissue damage by autoreactive T lymphocytes.Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection is characterized by an inflammatory dysregulation that has been associated with the development of autoimmune processes[1].