title: Causality assessment methods in drug induced liver injury: strengths and weaknesses.
abstract: Diagnosis of drug-induced liver injury (DILI) remains a challenge and eagerly awaits the development of reliable hepatotoxicity biomarkers. Several methods have been developed in order to facilitate hepatotoxicity causality assessments. These methods can be divided into three categories: (1) expert judgement, (2) probabilistic approaches, and (3) algorithms or scales. The last category is further divided into general and liver-specific scales. The Council for International Organizations of Medical Sciences (CIOMS) scale, also referred to as the Roussel Uclaf Causality Assessment Method (RUCAM), although cumbersome and difficult to apply by physicians not acquainted with DILI, is used by many expert hepatologists, researchers, and regulatory authorities to assess the probability of suspected causal agents. However, several limitations of this scale have been brought to light, indicating that a number of adjustments are needed. This review is a detailed timely criticism to alert the readers of the limitations and give insight into what would be needed to improve the scale. Instructions on how to approach DILI diagnosis in practice are provided, using CIOMS as an aid to emphasize the topics to be addressed when assessing DILI cases. Amendments of the CIOMS scale in the form of applying authoritative evidence-based criteria, a simplified scoring system and appropriate weighting given to individual parameters based on statistical evaluations with large databases will provide wider applicability in the clinical setting.
authors.affiliation: Unidad de Hepatología, Servicio de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Campus Universitario de Teatinos sn, 29010 Málaga, Spain.
authors.forename: Miren
authors.initials: M
authors.lastname: García-Cortés
authors.affiliation: Servicio de Farmacología Clínica, Grupo de Estudio para las Hepatopatías Asociadas a Medicamentos, Co-ordinating Centre, Hospital Universitario Virgen de la Victoria, Facultad de Medicina, Campus Universitario de Teatinos s/n, Málaga, Spain.
authors.forename: Camilla
authors.initials: C
authors.lastname: Stephens
authors.affiliation: Servicio de Farmacología Clínica, Grupo de Estudio para las Hepatopatías Asociadas a Medicamentos, Co-ordinating Centre, Hospital Universitario Virgen de la Victoria, Facultad de Medicina, Campus Universitario de Teatinos s/n, Málaga, Spain. Electronic address: lucena@uma.es.
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Lucena
authors.affiliation: Unidad de Hepatología, Servicio de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Campus Universitario de Teatinos sn, 29010 Málaga, Spain.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Fernández-Castañer
authors.affiliation: Unidad de Hepatología, Servicio de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Campus Universitario de Teatinos sn, 29010 Málaga, Spain.
authors.forename: Raúl J
authors.initials: RJ
authors.lastname: Andrade
mesh_terms: D000465:Algorithms; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis* / Q000209:etiology*; D006801:Humans; D008099:Liver / Q000187:drug effects