Isoniazid Administration and Liver Injury

Abstract

Isoniazid has been recognized as a cause of liver dysfunction in some patients receiving antituberculous therapy. The medical literature contains reports of isoniazid-induced hepatic injury in adults, but essentially none in children. We used this drug to treat a 6\ x =r eq-\ year-old Caucasian boy for active tuberculosis, and he suffered a reaction characterized by high fever, a morbilliform exanthem, peripheral eosinophilia, enlargement of the liver, and abnormal liver function and histologic findings. The histologic appearance of the liver lesion and the clinical manifestations were suggestive of a hypersensitivity reaction, probably of the delayed type.

Isoniazid liver injury during chemoprophylaxis in children.

“…Until recently no data ofhepatic function had been reported in children receiving INH for prophylaxis and the ad hoc Committee on Isoniazid and Liver Disease in Atlanta, Georgia, USA, stated in a report issued in 1971 that 'isoniazid-associated liver disease does not appear to occur in children.' Since then reports have suggested that severe hepatic injury (Rudoy et al, 1973) or even death (Vanderhoof and Ament, 1976) might occur in children taking INH. Beaudry et al (1974) who studied SGOT levels in 369 children on INH prophylaxis reported increased levels of SGOT in 6 8 % of them.…”

Antituberculosis Drug-Induced Hepatotoxicity in Children

“…Dosages of drugs reduced and INH continued at 10 mg/kgSurvivedLiver biopsy:Inflammation, intralobular and intracellular bile retention and fatty infiltrationRudoy et al 1973 109 6 yearsMale20 mg/kg SM 10 mg/kg-PAS 300 mg,4 weeksFever, arthralgia, maculopapular rash, abdominal pain. Role of INH confirmed on rechallengeSurvivedLiver biopsy:Focal mesenchymal reaction with non-tuberculous granulomasMerlin et al 1974 110 3.75 yearsFemale10 mg/kgSM 400 mg10 monthsRoutine liver evaluation found raised transaminase values, findings; resolved when INH stopped.SurvivedLiver biopsy:Histological evidence of hepatitis, infectious and drug-induced hepatitis indistinguishable.Casteels-VanDaele et al 1975 111 13 yearsFemale12 mg/kg11 mg/kgEMB 20 mg/kg7 daysLethargy, confusion.…”

Isoniazid-Hepatitis im Kindesalter

“…In adults, hepatotoxic side effects of isoniazid, especially when given simultaneously with rifampicin, are not unusual (5,17). In children, however, isoniazid hepatotoxieity has rarely been reported (7,10,26,31). In two children aged 4 and 13 years, respectively, we observed transaminase values rising above 1000 V/Ion the 7th resp.…”

“…Ausgeprägte hepatotoxische Nebenwirkungen des Isoniazid, insbesondere bei Kombination mit Rifampicin, sind bei Erwachsenen nicht selten (5,17), bei Kindern aber nur in vereinzelten Fällen beobachtet worden (7,10,26,31). Wir beobachteten zwei Kinder im Alter von 4 und 13 Jahren, bei denen 7 bzw.…”

“…Das Risiko für Erwachsene wurde mit weniger als 1%angegeben, bei Kindern sei eine Lebertoxizität von INH nicht zu erwarten (2). In den folgenden Jahren mehrten sich aber die Mitteilungen über schwere, teilweise letal verlaufende INH-Hepatitiden (11,16), vereinzelt wurden schwere Leberschädigungen auch bei Kindern beobachtet (6,7,10,26,30,31,32) Nach Verlegung in eine Tuberkuloseheilstätte wurde dort später eine INH-Monotherapie ( (21). Nach einer Woche bereits klinisch erheblich gebessertes Befinden, Appetit-und Gewichtszunahme, Laborwerte am 4.8.: GOT 47, GPT 406, GlDH 1,1 V/I, ChE 1084 V/I, Gallensäuren 461Jrnol/1.…”