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Copyright ©The Author(s) 2017.
World J Hepatol. Jan 8, 2017; 9(1): 30-37
Published online Jan 8, 2017. doi: 10.4254/wjh.v9.i1.30
Table 1 Similarities and differences between drug-induced torsade de pointes and drug-induced liver injury
DITdPDILI
Endpoint/biomarkerSurrogate, but well defined biomarker of risk (QT prolongation with specific thresholds)Surrogate, but well defined biomarker of risk (transaminase elevation with specific thresholds)
Key mechanismLargely described (dose-dependent hERG K+ channel inhibition)Only partially understood (different hypotheses)
Dose-response relationshipDose dependent (with only a few exceptions)Idiosyncratic, although dose-dependence exists
Regulatory impactPre-clinical and clinical guidelines (pre-marketing)Clinical guideline (pre-marketing)
Clinical impactSignificant (a leading cause of drug withdrawal worldwide)Significant (a leading cause of drug withdrawal worldwide)
Predictivity of pre-clinical assaysReasonably good (new models under investigation)Sub-optimal (especially for in vivo models)
Predictivity of clinical studiesGood (thorough QT study), albeit imperfectGood (Hy’s law), albeit imperfect
Role of geneticsImportant (long QT syndrome)Partially defined (only for some drugs)
Awareness (clinicians, regulators, drug developers, researchers)Significant at all levelsSignificant at some levels (drug developers, researchers)
Risk assessment tools (clinical)Drug- and patient-related risk factors are well recognized (https://www.crediblemeds.org/); CDSSs are under implementationDrug- and patient-related risk factors are only partially recognized (https://livertox.nlm.nih.gov/)
Causality assessment tools (clinical)Not present, but the majority of TdP cases are drug induced (the so-called designated medical event); phenotype standardizedSpecific, but challenging (several differential diagnoses)
TherapyMagnesium sulphate, electrical cardioversion or isoproterenol (isoprenaline) or transvenous pacing (refractory TdP cases); removal or correction of precipitants, including drugsNo specific treatment other than drug discontinuation; liver transplantation may be required in acute liver failure cases