A prospective study of antituberculous drug-induced hepatotoxicity in an area endemic for liver diseases

Purpose: Identification of risk factors associated with antituberculosis drug-induced hepatotoxicity (anti-TB-DIH) is important, especially in endemic area for TB and liver disease. This study assessed the incidence and risk factors of anti-TB-DIH in upper Egyptian patients treated for active pulmonary and extra-pulmonary TB. Methods: A total of 100 consecutive TB patients were prospectively followed up both clinically and biochemically before and during their course of anti-TB therapy with daily doses of isoniazid, rifampin, ethambutol, and pyrazinamide, or streptomycin. Results: Anti-TB-DIH developed in 15 (15%) patients within 15-60 days (median: 30 days) from the onset of therapy. Liver function normalized in 10 (60%) patients within 2 weeks from cessation of therapy. No recurrence of DIH was observed after reintroduction of therapy. Only 1 patient died from fulminant hepatic failure despite discontinuation of all anti-TB drugs. By univariate analysis, patients with anti-TB-DIH had more pre-existing liver disease (P = 0.024; OR: 3.60; 95% CI: 1.16-11.18), lower body mass index (BMI; P = 0.037; OR: 3.73; 95% CI: 1.04-10.56), lower serum albumin (P = 0.035; OR: 3.31; 95% CI: 1.04-10.56), and more extensive disease (P = 0.033; OR: 3.50; 95% CI: 1.11-11). Age, gender, raised baseline transaminases level, inclusion of pyrazinamide, and inactive hepatitis B or C carrier state were not significant risk factors of DIH. Using multivariate regression analysis, only pre-existing liver disease and lower BMI of 20 kg/m2 or less were independent predictors of DIH (P = 0.024 and P = 0.047, respectively). Conclusion: Anti-TB-DIH is not uncommon, needs early recognition and treatment, and is more in patients with pre-existing liver disease and low BMI. © Asian Pacific Association for the Study of the Liver 2008.