Hepatotoxicidad secundaria a “productos naturales”: análisis de los casos notificados al Registro Español de Hepatotoxicidad / No disponible

Introducción: la toxicidad hepática asociada al uso crecientede productos de “remedios naturales” es un fenómeno emergente.Objetivos: valoración de las características epidemiológicas,clínicas y demográficas de los casos de hepatotoxicidad secundariosa productos herbales (PH) y suplementos dietéticos(SD).Pacientes y métodos: análisis de los casos de hepatotoxicidaddebida a PH y SD incluidos en el Registro Español de Hepatotoxicidad.Resultados: trece casos de un total de 521 casos (2%) dereacciones adversas hepáticas incluidas en el registro entre1994 y 2006, eran secundarios a PH/SD, representando el décimogrupo terapéutico responsable por orden de frecuencia,por delante de analgésicos, ansiolíticos y antipsicóticos. Nuevepacientes (69%) eran mujeres y la edad media fue de 45 años.Nueve pacientes (69%) presentaron ictericia. El tipo de dañomás frecuente fue el hepatocelular (12; 92%) y un 31% de loscasos presentaron datos de hipersensibilidad. La sustancia máscomúnmente involucrada en los casos de daño hepático fue laCamellia sinensis (23%) seguida de Rhamnus purshianus eisoflavonas (Fitosoja®, Biosoja®) con dos casos cada uno (15%).Tres casos (23%) presentaron re-exposición positiva.Conclusiones: la hepatotoxicidad originada por PH/SD noes excepcional, y su perfil es la hepatitis aguda hepatocelular ictéricapredominantemente en mujeres. La frecuente ocurrenciade reexposición positiva en estos pacientes indica un bajo índicede sospecha y un retraso o ausencia de diagnóstico de estetipo de reacción adversa

Background: toxic liver damage associated with the use ofnatural remedies is a growing health problem.Objectives: to analyze the demographics, and clinical andepidemiological characteristics of patients developing liver injuryrelated to these remedies.Patients and methods: all DILI cases associated with the useof herbal remedies (HR) or dietary supplements (DS) submitted tothe Spanish Registry were analyzed. Type of liver damage, severity,and outcome were specifically evaluated.Results: thirteen cases out of 521 DILI cases (2%) submittedto the Spanish Liver Toxicity Registry between 1994 and2006 were related to HR/DS, which ranked as the 10th therapeuticgroup with a greater number of cases and above painkillers, anxiolytics, and antipsychotic drugs. Nine patients (69%)were female (mean age 45 years). Nine cases (69%) had jaundiceat presentation. The predominating type of liver damagewas hepatocellular (12; 92%), and 31% of cases exhibited thecommon features of hypersensitivity. Camellia sinensis (3,23%) was the main causative herb, followed by Rhamnus purshianusand isoflavones (Fitosoja®, Biosoja®) (2 cases each,15%). Three cases (23%) were rechallenged with the offendingproduct.Conclusions: the incidence of hepatic damage related toHR/DS is not so rare, the most common profile of affected patientsbeing a woman with acute hepatocellular hepatitis. Lowsuspicion regarding the putative role of herbs in hepatotoxicitymakes diagnosis more difficult, and probably increases the incidenceof inadvertent rechallenge in these patients

[An analysis of the causes, characteristics, and consequences of reexposure to a drug or compound responsible for a hepatotoxicity event]. / Análisis de las causas, características y consecuencias de la reexposición al fármaco o compuesto responsable de un episodio de hepatotoxidad.

INTRODUCTION: reexposure to a causal agent represents a potentially serious event in hepatotoxicity. OBJECTIVES: to assess the characteristics and outcome of cases with positive reexposure. MATERIAL AND METHODS: a retrospective study of cases with evidence of positive reexposure included in Registro Español de Hepatopatías Asociadas a Medicamentos, and an analysis of their relation to demographic and clinical variables, causality, course, and consequences. RESULTS: of a total of 520 cases 31 (6%) met reexposure criteria. Fatal outcomes, needs for admission, and mean recovery time were all higher for hepatocellular-type toxic injury. The most commonly identified drug class was antibiotics. On most occasions (73%) reexposure to the causal compound escaped notice because of: absence of index case diagnosis, lack of information to patients and their physicians, and (12%) development of cross reactions between structurally similar drugs. CONCLUSIONS: accidental reexposure to a drug or a structurally-related compound after an initial hepatotoxicity event is common and may have serious consequences, particularly in hepatocellular-type toxicity. Careful history taking and reflecting diagnostic suspicion in the initial episode s record may reduce the incidence of this iatrogenic event.

Análisis de las causas, características y consecuencias de la reexposición al fármaco o compuesto responsable de un episodio de hepatotoxicidad / No disponible

Introducción: la reexposición al agente causal constituye unincidente potencialmente grave en hepatotoxicidad.Objetivos: evaluar las características y la evolución de los casoscon reexposición positiva.Material y métodos: estudio retrospectivo de una serie decasos con evidencia de reexposición positiva incluidos en el RegistroEspañol de Hepatopatías Asociadas a Medicamentos, analizandosu relación con variables demográficas y clínicas, causalidad,evolución y consecuencias.Resultados: de un total de 520 casos, 31 (6%) cumplían loscriterios de reexposición. La evolución fatal, la necesidad de hospitalizacióny el tiempo medio de recuperación fueron mayores enla lesión tóxica de tipo hepatocelular. El grupo farmacológicoidentificado con mayor frecuencia fue el de los antibióticos. En lamayoría de los casos la reexposición con el compuesto responsablefue inadvertida (73%) debido a: la ausencia de diagnóstico delcaso índice, la carencia de información al paciente o a su médicoy también (12%) por el desarrollo de una reacción cruzada entrefármacos estructuralmente similares.Conclusiones: la reexposición accidental a un mismo fármacoo a otro estructuralmente relacionado tras un primer episodiode hepatotoxicidad no es infrecuente y sus consecuencias puedenser graves, especialmente en el tipo de lesión hepatocelular. Unaminuciosa historia clínica y la sospecha diagnóstica reflejada en elinforme del primer episodio podrían disminuir la incidencia deeste evento iatrogénico

Introduction: reexposure to a causal agent represents a potentiallyserious event in hepatotoxicity.Objectives: to assess the characteristics and outcome of caseswith positive reexposure.Material and methods: a retrospective study of cases withevidence of positive reexposure included in Registro Español deHepatopatías Asociadas a Medicamentos, and an analysis of theirrelation to demographic and clinical variables, causality, course,and consequences.Results: of a total of 520 cases 31 (6%) met reexposure criteria.Fatal outcomes, needs for admission, and mean recovery timewere all higher for hepatocellular-type toxic injury. The most commonlyidentified drug class was antibiotics. On most occasions(73%) reexposure to the causal compound escaped notice becauseof: absence of index case diagnosis, lack of information topatients and their physicians, and (12%) development of cross reactionsbetween structurally similar drugs.Conclusions: accidental reexposure to a drug or a structurally-related compound after an initial hepatotoxicity event is commonand may have serious consequences, particularly in hepatocellular-type toxicity. Careful history taking and reflectingdiagnostic suspicion in the initial episode’s record may reduce the incidence of this iatrogenic event (AU)

Evaluation of naranjo adverse drug reactions probability scale in causality assessment of drug-induced liver injury.

BACKGROUND: Causality assessment in hepatotoxicity is challenging. The current standard liver-specific Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale is complex and difficult to implement in daily practice. The Naranjo Adverse Drug Reactions Probability Scale is a simple and widely used nonspecific scale, which has not been specifically evaluated in drug-induced liver injury. AIM: To compare the Naranjo method with the standard liver-specific Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale in evaluating the accuracy and reproducibility of Naranjo Adverse Drug Reactions Probability Scale in the diagnosis of hepatotoxicity. METHODS: Two hundred and twenty-five cases of suspected hepatotoxicity submitted to a national registry were evaluated by two independent observers and assessed for between-observer and between-scale differences using percentages of agreement and the weighted kappa (kappa(w)) test. RESULTS: A total of 249 ratings were generated. Between-observer agreement was 45% with a kappa(w) value of 0.17 for the Naranjo Adverse Drug Reactions Probability Scale, while there was a higher agreement when using the Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale (72%, kappa(w): 0.71). Concordance between the two scales was 24% (kappa(w): 0.15). The Naranjo Adverse Drug Reactions Probability Scale had low sensitivity (54%) and poor negative predictive value (29%) and showed a limited capability to distinguish between adjacent categories of probability. CONCLUSION: The Naranjo scale lacks validity and reproducibility in the attribution of causality in hepatotoxicity.

[Liver injury induced by "natural remedies": an analysis of cases submitted to the Spanish Liver Toxicity Registry]. / Hepatotoxicidad secundaria a "productos naturales": análisis de los casos notificados al Reigstro Español de Hepatotoxicidad.

BACKGROUND: toxic liver damage associated with the use of natural remedies is a growing health problem. OBJECTIVES: to analyze the demographics, and clinical and epidemiological characteristics of patients developing liver injury related to these remedies. PATIENTS AND METHODS: all DILI cases associated with the use of herbal remedies (HR) or dietary supplements (DS) submitted to the Spanish Registry were analyzed. Type of liver damage, severity, and outcome were specifically evaluated. RESULTS: thirteen cases out of 521 DILI cases (2%) submitted to the Spanish Liver Toxicity Registry between 1994 and 2006 were related to HR/DS, which ranked as the 10th therapeutic group with a greater number of cases and above pain killers, anxiolytics, and antipsychotic drugs. Nine patients (69%) were female (mean age 45 years). Nine cases (69%) had jaundice at presentation. The predominating type of liver damage was hepatocellular (12; 92%), and 31% of cases exhibited the common features of hypersensitivity. Camellia sinensis (3, 23%) was the main causative herb, followed by Rhamnus purshianus and isoflavones (Fitosoja(R), Biosoja(R)) (2 cases each, 15%). Three cases (23%) were rechallenged with the offending product. CONCLUSIONS: the incidence of hepatic damage related to HR/DS is not so rare, the most common profile of affected patients being a woman with acute hepatocellular hepatitis. Low suspicion regarding the putative role of herbs in hepatotoxicity makes diagnosis more difficult, and probably increases the incidence of inadvertent rechallenge in these patients.