Hepatitis aguda por ticlopidina. Presentación de 12 casos y revisión de la literatura / Acute hepatitis due to ticloidine. A report of 12 cases and review of the literature

Objetivo. Analizar las características de la hepatotoxicidad por ticlopidina. Pacientes y métodos. Describimos todos los casos de hepatotoxicidad atribuidos a ticlopidina y remitidos al Registro de Hepatopatías asociadas a medicamentos e identificamos por MEDLINE e Índice Médico Español los casos publicados durante el período 1982-2001. Resultados. Se remitieron 12 casos de alteración hepática relacionada con ticlopidina, que constituyeron un 5 por ciento del total de casos de hepatotoxicidad notificados al Registro. El 83 por ciento de los pacientes eran varones con una edad media de 68 años. El 66 por ciento de éstos precisó ingreso hospitalario. El período de latencia varió de 2 a 13 semanas. El patrón de lesión hepática fue de tipo colestásico en el 75 por ciento de los casos, hepatocelular en el 16,6 por ciento y mixto en el 8,3 por ciento. El 25 por ciento de los pacientes recibió una dosis subterapéutica. Conclusiones. Ticlopidina se relaciona frecuentemente con hepatotoxicidad, que parece obedecer a un mecanismo idiosincrásico y es predominantemente de carácter colestásico. La utilización de dosis menores a la recomendadas, además de carecer del efecto terapéutico esperado, no protege del desarrollo de hepatotoxicidad. Los médicos que prescriben este medicamento deben estar informados de este potencial para establecer una correcta relación beneficio-riesgo (AU)

Flutamide-induced hepatotoxicity: report of a case series.

OBJECTIVE: To evaluate the characteristics of flutamide induced hepatotoxicity. MATERIAL AND METHODS: In this retrospective study we have analyzed all cases of flutamide hepatotoxicity submitted to the Andalucian Registry of drug-induced liver disease. Data were collected using a structured reporting form. Causality assessment was performed using two clinical scales: the standard CIOMS scale and the recently developed María and Victorino scale. RESULTS: Nine of 185 patients (4.9%) were identified. In 8 male patients, mean age 75 years (range 65-83), flutamide was indicated for palliative therapy of disseminated prostatic carcinoma, and in one young female (14 years) was given for the treatment of facial hirsutism. The mean duration of the flutamide therapy was 151 days (range 4-443). All patients presented with overt liver injury, the most frequent features being asthenia, anorexia, weight loss, nausea, vomiting and jaundice. No patient showed hypersensitivity features. In two patients (22%) the hepatic damage evolved to fulminant liver failure, one of them undergoing a liver transplantation and the other subsequently died. An additional patient died of a non-hepatic related cause when his liver function was improving. Causality assessment by the two clinical scales did not exclude any case, but the two patients who died where classified as unlikely by the María and Victorino scale. CONCLUSIONS: Flutamide can induce severe acute hepatitis, probably due to an idiosyncratic metabolic mechanism. Liver tests monitoring should probably be mandatory during the first months of flutamide therapy and the drug withdrawn if transaminases began to increase.

Hepatotoxicidad por flutamida: análisis de una serie / Flutamide-induced hepatotoxicity: report of a case series

Objetivo: evaluar las características de la hepatotoxicidad por flutamida.Material y métodos: análisis de 9 casos de toxicidad hepática secundaria a este fármaco remitidos al Registro Andaluz de Hepatopatías asociadas a medicamentos. La información se recogió en un protocolo estructurado. La imputabilidad de la flutamida se estimó en cada uno de los casos por dos escalas diagnósticas; Council for International Organization of Medical Sciences (CIOMS) y una recientemente validada (María y Victorino).Resultados: 9 de 185 casos (4,9 por ciento) de hepatotoxicidad remitidos al registro eran debidos a flutamida. En 8 pacientes varones con edad media de 75 años (rango 65-83), la flutamida se indicó para la paliación del carcinoma de próstata metastásico, y en una mujer de 14 años para el tratamiento del hirsutismo facial. El tiempo medio de duración del tratamiento fue de 151 días (rango 4-433). El episodio de hepatotoxicidad tuvo expresión clínica en todos los pacientes, siendo las manifestaciones más frecuentes: astenia, anorexia, pérdida de peso, náuseas, vómitos e ictericia. Ningún paciente presentó manifestaciones de hipersensibilidad. Dos pacientes (22 por ciento) presentaron fallo hepático fulminante, falleciendo uno y realizándose transplante hepático en el otro. Un tercer paciente falleció cuando la lesión hepática estaba en fase de resolución. No hubo ningún caso excluido en la evaluación de im putabilidad, pero los dos casos de éxitus fueron clasificados como dudosos por la escala de María y Victorino. Conclusiones: flutamida puede producir hepatitis aguda grave, ocasionalmente fulminante, por un mecanismo presuntamente de idiosincrasia metabólica. Debería monitorizarse el perfil hepático durante los primeros meses de tratamiento con flutamida, suspendiéndose el fármaco en caso de detectarse alteraciones (AU)

[Acute hepatitis due to ticlopidine. A report of 12 cases and review of the literature]. / Hepatitis aguda por ticlopidina. Presentación de 12 casos y revisión de la literatura.

OBJECTIVE: To analyze the characteristics of hepatotoxicity due to ticlopidine. PATIENTS AND METHODS: We describe all the case of hepatotoxicity attributed to ticlopidine and reported to the Register of drug associated hepatopathies. We also obtained data from MEDLINE and the Spanish Medical Index regarding cases reported during the period 1982 2001. RESULTS: We reported twelve cases of hepatopathy related to the use of ticlopidine. These made up 5% of all the cases notified to the Register. Eighty three percent of the patients were male, and of an average age of 68 years. Sixty six percent required hospital admission. The latent period varied between 2 and 13 weeks. The liver lesion was of cholestatic type in 75% of the cases, hepatocellular in 16.6% and mixed in 8.3%. Twenty five percent of the patients had received sub therapeutic doses. CONCLUSIONS: Ticlopidine is often related to hepatotoxicity. This seems to be due to an idiosyncratic mechanism and is mainly cholestatic. The use of lower dosage than that recommended means that the desired therapeutic effect is not attained but does not protect against the development of hepatotoxicity. Doctors who use this drug should be aware of this so as to establish the true risk benefit relation.

[Pneumonitis caused by mesalazine]. / Neumonitis por mesalazina.

5-aminosalicylic acid (5-ASA) has been used to treat inflammatory bowel disease satisfactorily. Lung disease related to 5-ASA administration has been described only rarely. We report a case of alveolitis related to 5-ASA treatment in a woman with Crohn's disease. We review the literature and describe clinical, biological and radiological manifestations, along with the clinical course of this complication.

[Treatment of chronic non-A, non-B-C hepatitis]. / Tratamiento de la hepatitis crónica NANB-C.

Preventive measures, and particularly screening for anti-HCV donors, have diminished the incidence of HCV infections, however, a vaccine against the disease is necessary for an effective prevention. The most active treatment at this time, seems to be alpha-interferon, at the dosage of 3 MU during 6 months. Possibly larger doses during longer periods of time might improve response and recurrence indexes, but not sufficiently as to give indiscriminate treatment to all patients at great cost and with many adverse reactions. While waiting for better predictive factors, the most convenient therapy remains the indicated dosage during 6 months, followed by periodic assessment during 2-3 months of transaminase levels: if they remain normal, the patient should be reassessed later on, if there is a recurrence, another course of treatment should be tried; non-responders should not be treated again with single interferon; other combinations or different treatments should be tried.

[Epidemiology of primary biliary cirrhosis in the South area of Granada]. / Epidemiología de la cirrosis biliar primaria en el área sur de Granada.

BACKGROUND: The epidemiology of primary biliary cirrhosis (PBC) in Spain is still poorly known. In fact, remarkable differences between areas have been found. METHODS: The epidemiology of PBC was investigated in the South area of the city and the province of Granada from 1976 through 1989. Several clinical and epidemiological data were collected from 25 patients who met the criteria for PBC and the yearly incidence and prevalence were calculated. RESULTS: The ages of patients which PBC ranged from 31 to 74 years (mean age 50 +/- 10.5); 88% were females and 28% were diagnosed in the asymptomatic phase of the disease. The incidence for the study period was variable, with a maximum of 6.8 cases/million and an overall yearly incidence rate of 4.1 +/- 2.3 cases/million (7.1 +/- 4.3 cases/million for females). When the risk population was considered (people over 25 years) the respective values were 11.5 and 6.9 +/- 3.7 cases/million (12.1 +/- 7.2 cases/million for females). The prevalence showed a progressive increase, being 36.4 cases/million at the end of the study; for the "risk" population it was 61.5/million (100 cases/million for females). CONCLUSIONS: Incidence and prevalence of PBC in the area of study are within medium and medium-high values for Spain and Europe. As in other studies, personal environmental or social factors with epidemiological significance were not identified.

[Acute pseudo-obstruction of the colon, a problem of old age. A study of 5 cases treated medically]. / La pseudobstrucción aguda del colon, un problema de la tercera edad. Estudio de cinco casos tratados médicamente.

Acute partial obstruction of the colon is a frequent complaint among elderly patients, this being the reason for the increase in incidence. 5 cases which were medically treated successfully are presented. The proper terminology is briefly discussed, describing the typical clinical features and the associated diseases which appear in 80-90% of cases. The diagnosis is basically clinical and plain abdominal X-Ray, barium enema and/or colonoscopy are the most helpful tests to make a differential diagnosis between mechanical and nonmechanical obstruction. An in-depth view on colonoscopy as a diagnostic and therapeutic method is presented.