Hepatotoxicity due to antituberculosis therapy. Clinical profile and reintroduction of therapy

The clinical profile of antituberculosis treatment (ATT)-induced hepatotoxicity is variable, and the reintroduction of ATT in patients who have developed such injury is controversial. We conducted a prospective study to determine the clinical profile in patients with ATT-induced hepatotoxicity and to test a predefined strategy of reintroduction of ATT. Seventy-two consecutive patients with clinical evidence of ATT-induced hepatotoxicity were included. Jaundice was the presenting symptom in 44 (61%) patients; prodromal symptoms were present in 28 (39%). Serious complications developed in 12 (16.6%) patients (fulminant hepatic failure in seven, subacute hepatic failure in four, hepatic encephalopathy in one). Nine patients (three males, six females) died from these complications. The mean duration of treatment before the onset of hepatitis was significantly longer in the group that died (53.22 +/- 36.22 days) than in the rest of the patients (31.07 +/- 30.30 days; p < 0.01). Malnutrition was present in 37 of the 72 patients. After resolution of drug induced hepatitis, reintroduction of isoniazid and rifampicin was possible in 41 of 44 patients. Thus, our results showed that ATT-induced hepatitis carried significant morbidity and mortality, that malnutrition was common in patients with ATT-related hepatitis, and that potentially hepatotoxic antituberculosis agents could be safely reintroduced after recovery from hepatitis.