Hepatotoxicity of anti-tuberculosis chemotherapy in patients with liver cirrhosis

OBJECTIVE: To determine whether liver cirrhosis patients are at higher risk for drug-induced hepatotoxicity (DIH) than control subjects during treatment for tuberculosis (TB) with standard short-course regimens containing isoniazid (INH), rifampicin (RMP), ethambutol (EMB) and/or pyrazinamide (PZA). METHODS: Fifty liver cirrhosis patients with newly diagnosed active TB treated with INH, RMP, EMB and/or PZA were included in the study, along with 147 patients without liver disease selected as control subjects. DIH was defined as alanine aminotransferase (ALT) > 120 IU/l with hepatitis symptoms or ALT > 200 IU/l. RESULTS: The aetiology of the liver cirrhosis patients consisted of alcoholic liver cirrhosis (n = 37, 74%), hepatitis B (n = 10, 20%) and hepatitis C (n = 3, 6%). The mean Child-Pugh score of all liver cirrhosis patients was 7.0 ± 1.2. DIH was more frequently found in liver cirrhosis patients, but the difference was not statistically significant (8.0% vs. 2.7%, P = 0.115). INH and RMP were successfully rechallenged and maintained until the end of treatment in three of four liver cirrhosis patients with DIH. CONCLUSION: Although DIH developed more frequently in TB patients with liver cirrhosis, the apparent difference in the incidence of DIH did not achieve statistical significance. Most of the patients with DIH were successfully treated with a standard short-course regimen including INH and RMP.