Incidence of hepatotoxicity due to antitubercular medicines and assessment of risk factors

BACKGROUND: Antitubercular drugs cause derangement of hepatic function revealed by clinical examination and abnormal liver function test results. Potential hepatotoxicity of some of the first-line antitubercular agents remains a problem, especially during the initial period of treatment. OBJECTIVE: To determine the incidence of antitubercular drug-induced hepatotoxicity in a Nepalese urban population and assess the risk factors. METHOD: Fifty patients diagnosed with active tuberculosis infection with normal pretreatment liver function were monitored clinically as well as biochemically in a prospective cohort analysis. RESULTS: Antitubercular drugs were found to be associated with derangement of hepatic function, resulting in elevation of liver enzymes to a variable extent (t = -4.550, p < 0.01 for aspartate aminotransferase [AST]; t = -5.467, p < 0.01 for alanine aminotransferase [ALT] at 95% CI). Thirty-eight percent of patients had 2 times and 30% had >3 times elevation of ALT. Similarly, 40% and 29% of patients showed 2 and >3 times elevation of the AST level, respectively. Four patients (8%) developed drug-induced hepatotoxicity. Jaundice was the presenting symptom in all patients. The time interval for onset of hepatotoxicity after initiation of therapy was 12-60 days (median 28). Antitubercular drug-induced hepatotoxicity was found more often in younger patients (6% vs 2%; p = 0.368, OR 2.75). Female gender was also a higher risk (p = 0.219, OR 4.2). Most patients who had developed hepatitis were diagnosed per sputum-smear positive reactions. Nutritional status, assessed by body mass index and serum albumin level, was the next predisposing factor. CONCLUSIONS: A finding of an 8% incidence of hepatotoxicity is considerably high. Risk factors of hepatotoxicity included female gender, disease extent, and poor nutritional status. Timely detection and temporary withdrawal of the offending agent can completely cure antitubercular drug-induced hepatotoxicity.