Is drug-induced hepatitis related to the severity of tuberculous meningitis?

Abstract

Drug-induced hepatitis (DIH) occurs more commonly in tuberculous meningitis (TBM) than non-CNS tuberculosis. We evaluate DIH in TBM and its relationship with disease severity and surrogate markers of stress. Sixty-seven patients with TBM were included prospectively. The diagnosis of DIH was based on five times elevation of alanine amino transferase (ALT) in asymptomatic and three times in symptomatic patients, serum bilirubin 1.5 mg/dL or more occurring after 3 days of antitubercular drugs without any other cause of liver dysfunction; and improvement in liver function upon drug withdrawal. Stage of TBM, Glasgow Coma Scale (GCS) score, signs of raised intracranial pressure (ICP), ESR, C-reactive protein (CRP), systemic inflammatory response syndrome (SIRS), serum cortisol and MRI findings were noted on admission and during DIH. A total of 32.8% (22/67) patients with TBM developed DIH that was associated with worsening in GCS score (p=0.01), stage TBM (p=0.02), SIRS parameters (p=0.04), ESR (p=0.04) and CRP (p<0.01) compared with their baseline. Stage of TBM independently predicted DIH (OR=0.42, 95% CI, 0.18-1.0; p=0.04)]. Drug-induced hepatitis occurred with paradoxical worsening in 11 patients and had higher mortality (32% vs 7%; p=0.01). DIH occurred in 32.8% (22/67) of patients with TBM, and was related to the severity of TBM and possibly to the accompanying 'physiological stress'.