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Drug-induced liver injury: recent advances in diagnosis and risk assessment

Idiosyncratic drug-induced liver injury (IDILI) is a rare but potentially severe adverse drug reaction that should be considered in patients who develop laboratory criteria for liver injury secondary to the administration of a potentially hepatotoxic drug. Although currently used liver parameters ar...

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Autores principales: Kullak-Ublick, Gerd A, Andrade, Raul J, Merz, Michael, End, Peter, Benesic, Andreas, Gerbes, Alexander L, Aithal, Guruprasad P
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5532458/
https://www.ncbi.nlm.nih.gov/pubmed/28341748
http://dx.doi.org/10.1136/gutjnl-2016-313369
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author Kullak-Ublick, Gerd A
Andrade, Raul J
Merz, Michael
End, Peter
Benesic, Andreas
Gerbes, Alexander L
Aithal, Guruprasad P
author_facet Kullak-Ublick, Gerd A
Andrade, Raul J
Merz, Michael
End, Peter
Benesic, Andreas
Gerbes, Alexander L
Aithal, Guruprasad P
author_sort Kullak-Ublick, Gerd A
collection PubMed
description Idiosyncratic drug-induced liver injury (IDILI) is a rare but potentially severe adverse drug reaction that should be considered in patients who develop laboratory criteria for liver injury secondary to the administration of a potentially hepatotoxic drug. Although currently used liver parameters are sensitive in detecting DILI, they are neither specific nor able to predict the patient's subsequent clinical course. Genetic risk assessment is useful mainly due to its high negative predictive value, with several human leucocyte antigen alleles being associated with DILI. New emerging biomarkers which could be useful in assessing DILI include total keratin18 (K18) and caspase-cleaved keratin18 (ccK18), macrophage colony-stimulating factor receptor 1, high mobility group box 1 and microRNA-122. From the numerous in vitro test systems that are available, monocyte-derived hepatocytes generated from patients with DILI show promise in identifying the DILI-causing agent from among a panel of coprescribed drugs. Several computer-based algorithms are available that rely on cumulative scores of known risk factors such as the administered dose or potential liabilities such as mitochondrial toxicity, inhibition of the bile salt export pump or the formation of reactive metabolites. A novel DILI cluster score is being developed which predicts DILI from multiple complimentary cluster and classification models using absorption–distribution–metabolism–elimination-related as well as physicochemical properties, diverse substructural descriptors and known structural liabilities. The provision of more advanced scientific and regulatory guidance for liver safety assessment will depend on validating the new diagnostic markers in the ongoing DILI registries, biobanks and public–private partnerships.
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spelling pubmed-55324582017-07-31 Drug-induced liver injury: recent advances in diagnosis and risk assessment Kullak-Ublick, Gerd A Andrade, Raul J Merz, Michael End, Peter Benesic, Andreas Gerbes, Alexander L Aithal, Guruprasad P Gut Recent Advances in Clinical Practice Idiosyncratic drug-induced liver injury (IDILI) is a rare but potentially severe adverse drug reaction that should be considered in patients who develop laboratory criteria for liver injury secondary to the administration of a potentially hepatotoxic drug. Although currently used liver parameters are sensitive in detecting DILI, they are neither specific nor able to predict the patient's subsequent clinical course. Genetic risk assessment is useful mainly due to its high negative predictive value, with several human leucocyte antigen alleles being associated with DILI. New emerging biomarkers which could be useful in assessing DILI include total keratin18 (K18) and caspase-cleaved keratin18 (ccK18), macrophage colony-stimulating factor receptor 1, high mobility group box 1 and microRNA-122. From the numerous in vitro test systems that are available, monocyte-derived hepatocytes generated from patients with DILI show promise in identifying the DILI-causing agent from among a panel of coprescribed drugs. Several computer-based algorithms are available that rely on cumulative scores of known risk factors such as the administered dose or potential liabilities such as mitochondrial toxicity, inhibition of the bile salt export pump or the formation of reactive metabolites. A novel DILI cluster score is being developed which predicts DILI from multiple complimentary cluster and classification models using absorption–distribution–metabolism–elimination-related as well as physicochemical properties, diverse substructural descriptors and known structural liabilities. The provision of more advanced scientific and regulatory guidance for liver safety assessment will depend on validating the new diagnostic markers in the ongoing DILI registries, biobanks and public–private partnerships. BMJ Publishing Group 2017-06 2017-03-23 /pmc/articles/PMC5532458/ /pubmed/28341748 http://dx.doi.org/10.1136/gutjnl-2016-313369 Text en Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/ This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
spellingShingle Recent Advances in Clinical Practice
Kullak-Ublick, Gerd A
Andrade, Raul J
Merz, Michael
End, Peter
Benesic, Andreas
Gerbes, Alexander L
Aithal, Guruprasad P
Drug-induced liver injury: recent advances in diagnosis and risk assessment
title Drug-induced liver injury: recent advances in diagnosis and risk assessment
title_full Drug-induced liver injury: recent advances in diagnosis and risk assessment
title_fullStr Drug-induced liver injury: recent advances in diagnosis and risk assessment
title_full_unstemmed Drug-induced liver injury: recent advances in diagnosis and risk assessment
title_short Drug-induced liver injury: recent advances in diagnosis and risk assessment
title_sort drug-induced liver injury: recent advances in diagnosis and risk assessment
topic Recent Advances in Clinical Practice
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5532458/
https://www.ncbi.nlm.nih.gov/pubmed/28341748
http://dx.doi.org/10.1136/gutjnl-2016-313369
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