Liver injury during antituberculosis treatment: An 11-year study

doi:10.1016/S0962-8479(96)90098-2

Tubercle and Lung Disease

Volume 77, Issue 4, August 1996, Pages 335-340

Tubercle and Lung Di...

https://doi.org/10.1016/S0962-8479(96)90098-2 Get rights and content

Abstract

Setting: Bispebjerg Hospital, Department of Pulmonary Medicine, tuberculosis referral center for the Municipality of Copenhagen.

Objective: To evaluate routine procedure for the management of liver injury during antituberculosis treatment.

Design: From 1983–1993, 765 patients for whom we could trace 752 files (98%) were treated at our ward with standard Danish treatment for tuberculosis. From 1983–1986 they received a three-drug (9-month) regimen and from 1986–1993 a four-drug (6-month) regimen consisting of isoniazid, rifampicin, ethambutol + pyrazinamide. Data from a retrospective chart review.

Results: An increase in aspartate aminotransferase (AST) of more than twice the upper limit of normal (ULN) was recorded in 127 patients (16%). 66 had elevated AST before treatment; most of these were men with a daily alcohol consumption in excess of 60 g. In the remaining 61 patients (8%) AST increased during antituberculosis treatment. 30 of these patients were excessive alcohol consumers, and seven had alcoholic liver cirrhosis. Despite an increase in AST of median 6 × ULN (range 2–25 × ULN), it was possible to continue treatment in 31 (15 excessive alcohol consumers) or reintroduce it fully in 14 (12 excessive alcohol consumers). Only 16 patients (2%), including 11 women with no daily alcohol consumption, needed a modified regimen. These patients were older (P < 0.05), seven were jaundiced, and one had alcoholic liver cirrhosis. Hepatotoxicity was confirmed by challenge with pyrazinamide (n = 7), isoniazid (n = 6) and combined isoniazid/rifampicin (n = 1). No deaths were caused by hepatotoxicity.

Conclusion: In spite of an increase in AST levels to approximately 6 × ULN during antituberculosis treatment, the drugs can be continued or reintroduced in full in most cases. Risk factors of hepatotoxicity included old age, female sex and extensive tuberculosis, and not alcohol consumption. Overall, hepatotoxicity during antituberculosis treatment can be monitored and managed easily.

Résumé

Cadre: Hôpital Bispebjerg, Département de Médecine Respiratoire, centre de référence pour la tuberculose pour la ville de Copenhagen.

Objectif: Evaluer l'attitude adoptée en routine en face d'atteintes hépatiques survenant au cours du traitement antituberculeux.

Schéma: Entre 1983 et 1993, 765 patients (dont 752 dossiers [98%] ont pu être retrouvés) ont été traités dans notre service selon le schéma danois de routine pour la tuberculose. De 1983 à 1986, il s'agissait d'un traitement de 9 mois à 3 drogues et de 1986 à 1993, d'un traitement de 6 mois avec 4 drogues, en l'occurrence isoniazide, rifampicine, ethambutol et éventuellement pyrazinamide. Les données proviennent d'une étude rétrospective des dossiers.

Résultats: L'on a relevé chez 127 patients (16%) une augmentation de l'aspartate amino transférase (AST) supérieure à deux fois la valeur limite supérieure de la normale. Chez 66 patients, l'AST était déjà augmentée avant le traitement, la plupart du temps chez des hommes dont la consommation quotidienne d'alcool était supérieure à 60 grammes. Chez les 61 patients restants (8%), l'augmentation d'AST est survenue au cours du traitement antituberculeux. Chez 30 de ces patients, on note une consommation alcoolique excessive et chez 7 une cirrhose hépatique d'origine alcoolique. Malgré une augmentation médiane des AST de 6 fois la limite supérieure de la normale (extrêmes: 2 à 25 fois la limite supérieure de la normale), l'on a pu poursuivre le traitement chez 31 patients (dont 15 consommateurs de doses excessives d'alcool) ou le réintroduire complétement chez 14 (dont 12 consommateurs de doses excessives d'alcool). Une modification du régime thérapeutique n'a été nécessaire que chez 16 patients (2%) dont 11 femmes sans consommation quotidienne d'alcool. Chez ces patients, l'age est plus élevé (P < 0,05), la jaunisse présente chez 7, et la cirrhose hépatique alcoolique chez 1. La toxicité hépatique du médicament a été confirmée par une épreuve de provocation à la pyrazinamide (n = 7), à l'isoniazide (n = 6) ou à la combinaison d'isoniazide et de rifampicine (n = 1). Aucun décés n'a été provoqué par l'hépatotoxicité.

Conclusion: Malgré l'augmentation des AST jusqu'à des valeurs environ six fois supérieures à la limite normale supérieure au cours du traitement antituberculeux, la médication a pu être poursuivie ou reprise complètement dans la plupart des cas. Les facteurs de risque pour l'hépatotoxicité comportent l'âge avancé, le sexe féminin et une tuberculose étendue et non la consommation d'alcool. Dans l'ensemble, l'hépatotoxicité au cours du traitement antituberculeux peut être facilement surveillée et maîtrisée.

Resumen

Marco de referencia: Departamento de Medicina Pulmonar, Hospital Bispebjerg, centro de referencia en tuberculosis de la Municipalidad de Copenhague.

Objetivo: Evaluar los procedimientos de rutina para el manejo del compromiso hepático durante el tratamiento antituberculoso.

Método: De 1983 a 1993, tratamos 765 enfermos, de los cuales 752 (98%) tenían registros, con el tratamiento de rutina para la tuberculosis de Dinamarca ; entre 1983 y 1986 se utilizó un régimen de 9 meses con tres medicamentos y entre 1986 y 1993 un regimen de 6 meses con cuatro medicamentos : isoniacida, rifampicina, etambutol + pirazinamida. Se estudian los datos de las fichas clínicas en forma retrospectiva.

Resultados: En 127 pacientes (16%) se registró un aumento de la aminotransferasa aspartato (AST) de más de 2 veces el límite superior normal (ULN). En 66 pacientes la AST había aumentado antes del tratamiento, la mayoría de éstos siendo hombres con consumo diario de alcohol de más de 60 g. En los 61 pacientes restantes (8%) la AST aumentó durante el tratamiento antituberculoso. Treinta (30) de estos pacientes eran consumidores excesivos de alcohol y 7 tenían cirrosis hepática de origen alcohólico. A pesar de un aumento de la AST con una mediana de 6 × ULN (rango 2–25 × ULN), el tratamiento se pudo continuar en 31 pacientes (15 consumidores excesivos de alcohol), o bien volver a comenzar a dosis normales en 14 (12 consumidores excesivos de alcohol). Sólo 16 pacientes (2%), incluyendo 11 mujeres sin consumo diario de alcohol, tuvieron que recibir un régimen de tratamiento modificado. Estos pacientes tenían más edad (P < 0,05), 7 tenían ictericia y uno tenía cirrosis hepática alcohólica. La hepatotoxicidad fue confirmada con prueba de provocación a la pirazinamida (n = 7), isoniacida (n = 6) y asociación isoniacida-rifampicina (n = 1). No se constataron muertes debidas a la hepatotoxicidad.

Conclusión: A pesar de un aumento de la AST a alrededor de 6 × ULN durante el tratamiento antituberculoso, la administración de los medicamentos pudo continuarse o reanudarse a dosis normales en la mayoría de los casos. Los factores de riesgo de hepatotoxicidad incluyen la edad avanzada, el sexo femenino y enfermedad tuberculosa extensiva, pero no el consumo de alcohol. En su conjunto, la hepatotoxicidad durante el tratamiento antituberculoso puede ser manejada con facilidad.

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Original articleLiver injury during antituberculosis treatment: An 11-year study

Abstract

Résumé

Resumen

Tubercle

J Hepatol

Gastroenterol

Tubercle Lung Dis

Tubercle

Lancet

The hepatic toxicity of antituberculosis regimens containing isoniazid, rifampicin and pyrazinamide

Tubercle

Predisposing factors in hepatitis induced by isoniazid-rifampicin treatment of tuberculosis

Am Rev Respir Dis

Hepatic dysfunction in undernourished patients receiving isoniazid and rifampicin

Top Geograph Med

Pulmonary tuberculosis with chemotherapy related dysfunction

Kakkaku

Hepatotoxicidad del tratamiento de la tuberculosis

Med Clin (Barc)

Hepatic complications of antituberculous therapy

Quat J Med

Short-course chemotherapy

Chest

Six-month isoniazid-rifampicin therapy for tuberculosis

Am Rev Respir Dis

USPHS tuberculosis short-course chemotherapy trial 21: effectiveness, toxicity, and acceptability

Ann Int Med

Toxic affects of isoniazid in tuberculosis chemoprophylaxis

J Am Med Ass

Original article
Liver injury during antituberculosis treatment: An 11-year study