Isoniazid-associated hepatitis in 114 patients

Area of Science:

• Hepatology
• Pharmacology
• Infectious Disease Epidemiology

Background:

• Isoniazid is a key drug for tuberculosis chemoprophylaxis.
• Overt hepatic disease is a known, serious adverse effect of isoniazid therapy.

Purpose of the Study:

• To analyze the characteristics and outcomes of isoniazid-induced hepatic disease.
• To identify risk factors associated with severe or fatal isoniazid hepatotoxicity.

Main Methods:

• Retrospective analysis of 114 patients who developed overt hepatic disease during isoniazid chemoprophylaxis.
• Histological examination of liver tissue from affected patients.
• Correlation of clinical presentation, timing of injury, bilirubin levels, and patient demographics with outcomes.

Main Results:

• The hepatic injury was predominantly hepatocellular, with a 12.3% fatality rate (13 deaths).
• Submassive or massive necrosis was observed in 13 patients.
• Hepatic injury onset after two months and elevated bilirubin levels (>20 mg/dL) were associated with a higher risk of fatal outcomes.
• Black females exhibited a significantly higher case fatality rate compared to other demographic groups.

Conclusions:

• Isoniazid-induced liver injury is a severe complication of tuberculosis chemoprophylaxis.
• Delayed onset and higher bilirubin levels predict a poorer prognosis.
• The findings suggest hepatotoxic metabolites, rather than hypersensitivity, may be responsible for isoniazid hepatotoxicity.