Hepatic enzyme abnormalities in children on triple therapy for tuberculosis

Standard chemotherapy for tuberculosis (TB) in children uses hepatotoxic drugs. Published data and guidelines on monitoring of liver function during TB treatment are often contradictory and not directly relevant to the pediatric 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, rifampicin, and isoniazid in standard recommended doses. Children on other hepatotoxic drugs were excluded. Measurements of liver function tests (LFT) included aspartate transaminase (AST), alanine transaminase (ALT), and bilirubin, and they were checked before and a median of 5 times (1-23) during treatment. Only one child had mildly abnormal LFTs pretreatment. Thirteen children (n = 13, [30%]; age 7.6 years, 1.8-10.9; 54% male; 77% Caucasian) developed abnormal LFTs (> mean + 2 SD) and of these 10 had TB disease. Eight of the 13 had mildly elevated enzymes (< twice upper limit of normal) while in five, all with disease, the enzymes were more markedly raised. In the group with normal LFTs (n = 30, [70%]; age 6.6 years 0.7-15.1; 47% male; 70% Caucasian) 25 had disease (83%). Liver enzyme elevation occurred early (1.65 weeks, 0.6-16.6). Only two children had symptoms (one jaundice, one pruritus) with treatment being stopped temporarily only in the jaundiced 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 are rare. Current British Thoracic Society and American Thoracic Society guidelines (that if LFTs are normal prior to treatment then further monitoring should only be performed if clinically indicated) seem adequate for children.