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Hepatic enzyme abnormalities in children on triple therapy for tuberculosis
1Department of Respiratory Paediatrics, Royal Hospital for Sick Children, Glasgow, Scotland.
Insights
Elevated liver enzymes are common in children undergoing tuberculosis (TB) triple therapy, often appearing early. Symptoms are rare, and monitoring guidelines appear adequate for pediatric TB treatment.
Area of Science:
- Pediatric Infectious Diseases
- Hepatology
- Pharmacology
Background:
- Standard tuberculosis (TB) chemotherapy in children involves hepatotoxic drugs.
- Existing guidelines for monitoring liver function during TB treatment are often contradictory and not pediatric-specific.
Purpose of the Study:
- To assess the frequency and pattern of liver function test (LFT) abnormalities in children treated with standard triple therapy for TB.
- To evaluate the adequacy of current monitoring guidelines for pediatric TB patients.
Main Methods:
- Prospective monitoring of 43 children (median age 6.6 years) receiving pyrazinamide, rifampicin, and isoniazid for TB.
- Regular measurement of aspartate transaminase (AST), alanine transaminase (ALT), and bilirubin before and during treatment.
- Exclusion of children on other hepatotoxic medications.
Main Results:
- 30% of children (13/43) developed abnormal LFTs, predominantly in those with active TB disease.
- Liver enzyme elevations typically occurred early in treatment (median 1.65 weeks) and were often mild.
- Only two children experienced symptoms, and LFTs normalized in most cases without treatment interruption.
Conclusions:
- Elevated LFTs are common in pediatric TB patients on triple therapy but are usually asymptomatic and transient.
- Current British Thoracic Society and American Thoracic Society guidelines for LFT monitoring appear sufficient for children receiving TB treatment.
Abstract:
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.