Hepatic toxicity during chemotherapy for severe tuberculosis meningitis

Area of Science:

• Pediatrics
• Infectious Diseases
• Hepatology

Background:

• Tuberculous meningitis (TBM) is a severe form of tuberculosis affecting young children.
• Standard treatment regimens involve multiple drugs, including isoniazid, rifampin, pyrazinamide, and ethionamide.
• Hepatotoxicity is a potential concern with these medications, especially at high dosages.

Purpose of the Study:

• To assess the risk of hepatotoxic effects in young children treated for severe TBM with high-dose anti-tuberculosis drugs.
• To evaluate liver function test abnormalities during treatment for TBM.

Main Methods:

• A cohort of 56 young children (median age, 22 months) with severe TBM was studied.
• Liver function tests, including serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase, were monitored.
• Children were observed for varying periods, with a subset followed for at least eight weeks.

Main Results:

• Only one child developed jaundice, likely due to a concurrent hepatitis A infection.
• In 33 children observed for ≥8 weeks, only 15% had consistently normal liver enzymes.
• Elevated AST/ALT levels (>200 U/L) were infrequent (3 patients), and enzyme levels tended to normalize.
• Children with stage III TBM exhibited higher enzyme levels than those with stage II.
• Among 23 children observed for a shorter period (mean 4 weeks), 75% had at least one abnormal liver function test.

Conclusions:

• High-dose anti-tuberculosis drug regimens for severe TBM in young children are generally associated with mild and transient liver enzyme elevations.
• Severe hepatotoxicity is uncommon, but careful monitoring of liver function is warranted, particularly in advanced stages of TBM.