Hepatic enzyme abnormalities in children on triple therapy for tuberculosis

Standard chemotherapy for tuberculosis (TB) in children uses hepatotoxic dr ugs. Published data and guidelines on monitoring of liver function during T B treatment are often contradictory and not directly relevant to the pediat ric population. We carefully monitored 43 children (age 6.6 years, 0.7-15.1 [median, range]; 49% male; 72% Caucasian) being treated for TB infection ( n = 8) or disease (n = 35) with triple therapy, using pyrazinamide, rifampi cin, and isoniazid in standard recommended doses. Children on other hepatot oxic drugs were excluded. Measurements of liver function tests (LFT) includ ed aspartate transaminase (AST), alanine transaminase (ALT), and bilirubin, and they were checked before and a median of 5 times (1-23) during treatme nt. Only one child had mildly abnormal LFTs pretreatment, Thirteen children (n = 13, [30%]; age 7.6 years, 1.8-10.9; 54% male; 77% Ca ucasian) developed abnormal LFTs (> mean + 2 SD) and of these 10 had TB dis ease. Eight of the 13 had mildly elevated enzymes (< twice upper limit of n ormal) while in five, all with disease, the enzymes were more markedly rais ed. In the group with normal LFTs (n = 30, [70%]; age 6.6 years 0.7-15.1; 4 7% male; 70% Caucasian) 25 had disease (83%). Liver enzyme elevation occurr ed early (1.65 weeks, 0.6-16.6). Only two children had symptoms tone jaundi ce, one pruritus) with treatment being stopped temporarily only in the jaun diced child. Otherwise, LFTs normalized without interrupting treatment. We conclude that elevated liver enzymes are not uncommon in children receiving triple therapy for TB, generally occurring early in treatment. Symptoms ar e rare. Current British Thoracic Society and American Thoracic Society guid elines (that ii LFTs are normal prior to treatment then further monitoring should only be performed if clinically indicated) seem adequate for childre n. Pediatr Pulmonol. 1999; 27:37-42, (C) 1999 Wiley-Liss, Inc.