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.

Currently, pharmaceutical preparations are serious contributors to liver disease; hepatotoxicity ranking as the most frequent cause for acute liver failure and postcommercialization regulatory decisions. The diagnosis of hepatotoxicity remains a difficult task because of the lack of reliable markers for use in general clinical practice. To incriminate any given drug in an episode of liver dysfunction is a step-by-step process that requires a high degree of suspicion, compatible chronology, awareness of the drug's hepatotoxic potential, the exclusion of alternative causes of liver damage and the ability to detect the presence of subtle data that favors a toxic etiology. This process is time-consuming and the final result is frequently inaccurate. Diagnostic algorithms may add consistency to the diagnostic process by translating the suspicion into a quantitative score. Such scales are useful since they provide a framework that emphasizes the features that merit attention in cases of suspected hepatic adverse reaction as well. Current efforts in collecting bona fide cases of drug-induced hepatotoxicity will make refinements of existing scales feasible. It is now relatively easy to accommodate relevant data within the scoring system and to delete low-impact items. Efforts should also be directed toward the development of an abridged instrument for use in evaluating suspected drug-induced hepatotoxicity at the very beginning of the diagnosis and treatment process when clinical decisions need to be made. The instrument chosen would enable a confident diagnosis to be made on admission of the patient and treatment to be finetuned as further information is collected.

RESUMENIntroducción: la reexposición al agente causal constituye un incidente potencialmente grave en hepatotoxicidad.Objetivos: evaluar las características y la evolución de los casos con reexposición positiva.Material y métodos: estudio retrospectivo de una serie de casos con evidencia de reexposición positiva incluidos en el Registro Español de Hepatopatías Asociadas a Medicamentos, analizando su relación con variables demográficas y clínicas, causalidad, evolución y consecuencias.Resultados: de un total de 520 casos, 31 (6%) cumplían los criterios de reexposición. La evolución fatal, la necesidad de hospitalización y el tiempo medio de recuperación fueron mayores en la lesión tóxica de tipo hepatocelular. El grupo farmacológico identificado con mayor frecuencia fue el de los antibióticos. En la mayoría de los casos la reexposición con el compuesto responsable fue inadvertida (73%) debido a: la ausencia de diagnóstico del caso índice, la carencia de información al paciente o a su médico y también (12%) por el desarrollo de una reacción cruzada entre fármacos estructuralmente similares.Conclusiones: la reexposición accidental a un mismo fárma-co o a otro estructuralmente relacionado tras un primer episodio de hepatotoxicidad no es infrecuente y sus consecuencias pueden ser graves, especialmente en el tipo de lesión hepatocelular. Una minuciosa historia clínica y la sospecha diagnóstica reflejada en el informe del primer episodio podrían disminuir la incidencia de este evento iatrogénico.Palabras clave: Reexposición. Hepatotoxicidad. Enfermedad hepática inducida por fármacos. Efectos adversos hepáticos.

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