Comparison of two clinical scales for causality assessment in hepatotoxicity.

Servicio de Farmacología Clínica, Hospital Universitario Virgen de la Victoria, Facultad de Medicina, Campus Universitario de Teatinos s/n, Málaga, Spain.
Hepatology (Impact Factor: 11.19). 01/2001; 33(1):123-30. DOI: 10.1053/jhep.2001.20645
Source: PubMed

ABSTRACT This study was performed to compare the assessments of drug-induced liver injury obtained with 2 methods, the Council for International Organizations of Medical Sciences (CIOMS) scale and the recently validated Maria & Victorino (M&V) clinical scale, in cases submitted to a registry of hepatotoxicity. A total of 215 cases of hepatotoxicity reported with a structured reporting form were evaluated by 3 independent experts. Because of the use of multiple drugs, 228 ratings were generated. The probability of the diagnosis was classified as definitive, probable, possible, unlikely, or excluded, and evaluated for consistency with a weighted kappa statistical test. Absolute agreement between the 2 scales was observed in 42 cases (18%, weighted kappa 0.28) with disagreement of 1 level in 108 cases (47%), and of 2 levels in 70 cases (31%). The best correlation between the 2 scales was obtained for drug-induced liver injury involving a suggested immunoallergic mechanism: the disagreement was 1 level or less in 72% of the cases (34 of 48), compared with 60% of the cases (85 of 141) that involved a presumed idiosyncratic metabolic mechanism. The lowest agreement (6%) was observed in cases with evidence of cholestasis. No agreement was found in cases of fulminant hepatitis or death. The CIOMS scale showed better discriminative power and produced assessments closer to those of specialists. The performance of the M&V scale was poor in reactions with long latency periods (i.e., amoxycillin/clavulanic acid), evolution to chronicity after withdrawal (cholestatic pattern), or death.

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    ABSTRACT: . Análisis de todos los casos de toxicidad hepática secundaria a tetrabamato remitidos al registro andaluz de hepatopatías asociadas a medicamentos y comparación con los casos publicados en la bibliografía.Material Y Método. La información se recogió en un protocolo estructurado. La imputabilidad de tetrabamato se estimó en cada uno de los casos mediante la escala diagnóstica del Council for International Organizations of Medical Sciences (CIOMS).Resultados. Se han recogido 7 casos de hepatotoxicidad atribuible a tetrabamato de un total de 327 pacientes (2%), con una edad media 57 años (4 varones). En un 57% de los casos la indicación fue el temblor. El período de latencia osciló entre 15 y 730 días. El patrón de daño hepático fue predominantemente citolítico, sin presentar manifestaciones de hipersensibilidad. Todos los casos evolucionaron a la recuperación sin secuelas en 60-120 días. La imputabilidad de tetrabamato estimada mediante la escala diagnóstica de CIOMS define la relación causal como altamente probable en 6 casos y como probable en uno.Conclusión. Tetrabamato puede inducir hepatotoxicidad probablemente por un mecanismo de idiosincrasia metabólica. Teniendo en cuenta este hecho, y la existencia de alternativas terapéuticas más idóneas, el fármaco no debería indicarse en el tratamiento de la desintoxicación alcohólica.
    Gastroenterología y Hepatología 01/2002; 25(10):589-593. DOI:10.1016/S0210-5705(02)70321-X · 0.83 Impact Factor
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    ABSTRACT: Causality assessment is a critical step in establishing the diagnosis of drug induced liver injury (DILI) during drug development. DILI may resemble almost any type of liver disease, and often presents a serious challenge to clinical investigators and drug makers. The diagnosis of DILI is largely based upon a combination of a compatible clinical course, exclusion of all other reasonable causes, resemblance of clinical and pathological features to known features of liver injury due to the drug (i.e., "drug's signature"), and incidence of liver injury among patients treated with the drug compared to placebo or comparator. Causality assessment for suspected DILI is currently performed using either evaluation by physicians with expertise in liver disorders (i.e., expert opinion) or standardized scoring instruments such as the Roussel Uclaf Causality Assessment Method (RUCAM). Both approaches are widely used in the post marketing setting. Causality assessment based on expert opinion is considered superior to standardized instruments such as RUCAM, in the setting of drug development, and is currently the preferred approach during clinical trials. There is a need for a systematic revision of RUCAM that will render it more suitable for the setting of clinical trials and drug development. Careful monitoring and meticulous data collection during clinical trials are essential in all cases with established liver injury to allow for a proper causality assessment. A workshop was convened to discuss best practices for the assessment of drug-induced liver injury (DILI) in clinical trials. This publication is based on the conclusions of this workshop.
    Drug Safety 11/2014; 37 Suppl 1:47-56. DOI:10.1007/s40264-014-0185-4 · 2.62 Impact Factor
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May 20, 2014