title: Drug Induced Liver Injury: Can Biomarkers Assist RUCAM in Causality Assessment?
abstract: Drug induced liver injury (DILI) is a potentially serious adverse reaction in a few susceptible individuals under therapy by various drugs. Health care professionals facing DILI are confronted with a wealth of drug-unrelated liver diseases with high incidence and prevalence rates, which can confound the DILI diagnosis. Searching for alternative causes is a key element of RUCAM (Roussel Uclaf Causality Assessment Method) to assess rigorously causality in suspected DILI cases. Diagnostic biomarkers as blood tests would be a great help to clinicians, regulators, and pharmaceutical industry would be more comfortable if, in addition to RUCAM, causality of DILI can be confirmed. High specificity and sensitivity are required for any diagnostic biomarker. Although some risk factors are available to evaluate liver safety of drugs in patients, no valid diagnostic or prognostic biomarker exists currently for idiosyncratic DILI when a liver injury occurred. Identifying a biomarker in idiosyncratic DILI requires detailed knowledge of cellular and biochemical disturbances leading to apoptosis or cell necrosis and causing leakage of specific products in blood. As idiosyncratic DILI is typically a human disease and hardly reproducible in animals, pathogenetic events and resulting possible biomarkers remain largely undisclosed. Potential new diagnostic biomarkers should be evaluated in patients with DILI and RUCAM-based established causality. In conclusion, causality assessment in cases of suspected idiosyncratic DILI is still best achieved using RUCAM since specific biomarkers as diagnostic blood tests that could enhance RUCAM results are not yet available.
authors.affiliation: Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, D-63450 Hanau, Germany. rolf.teschke@gmx.de.|Teaching Hospital of the Medical Faculty, Goethe University Frankfurt, D-60590 Frankfurt, Germany. rolf.teschke@gmx.de.
authors.forename: Rolf
authors.initials: R
authors.lastname: Teschke
authors.affiliation: Institute of Occupational, Environmental and Social Medicine, Medical Faculty, Goethe University Frankfurt, D-60590 Frankfurt, Germany. j.schulze@em.uni-frankfurt.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Schulze
authors.affiliation: Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, D-63450 Hanau, Germany. Axel_Eickhoff@klinikum-hanau.de.|Teaching Hospital of the Medical Faculty, Goethe University Frankfurt, D-60590 Frankfurt, Germany. Axel_Eickhoff@klinikum-hanau.de.
authors.forename: Axel
authors.initials: A
authors.lastname: Eickhoff
authors.affiliation: Pharmacovigilance Consultancy, F-75020 Paris, France. gaby.danan@gmail.com.
authors.forename: Gaby
authors.initials: G
authors.lastname: Danan
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis*; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis*; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D012680:Sensitivity and Specificity; D015262:Xenobiotics / Q000009:adverse effects* / Q000145:classification
chemical_list: D015415:Biomarkers; D015262:Xenobiotics
keywords: DILI; RUCAM; Roussel Uclaf Causality Assessment Method; diagnostic biomarkers; drug induced liver injury; pathogenesis