LIVER-INJURY DURING ANTITUBERCULOSIS TREATMENT - AN 11-YEAR STUDY

Setting: Bispebjerg Hospital, Department of Pulmonary Medicine, tuberc ulosis referral center for the Municipality of Copenhagen. Objective: To evaluate routine procedure for the management of liver injury durin g antituberculosis treatment. Design: From 1983-1993, 765 patients for whom we could trace 752 files (98%) were treated at our ward with sta ndard Danish treatment for tuberculosis. From 1983-1986 they received a three-drug (9-month) regimen and from 1986-1993 a four-drug (6-month ) regimen consisting of isoniazid, rifampicin, ethambutol + pyrazinami de. Data from a retrospective chart review. Results: An increase in as partate aminotransferase (AST) of more than twice the upper limit of n ormal (ULN) was recorded in 127 patients (16%). 66 had elevated AST be fore treatment; most of these were men with a daily alcohol consumptio n in excess of 60 g. In the remaining 61 patients (8%) AST increased d uring antituberculosis treatment. 30 of these patients were excessive alcohol consumers, and seven had alcoholic liver cirrhosis. Despite an increase in AST of median 6 x ULN (range 2-25 x ULN), it was possible to continue treatment in 31 (15 excessive alcohol consumers) or reint roduce it fully in 14 (12 excessive alcohol consumers). Only 16 patien ts (2%), including 11 women with no daily alcohol consumption, needed a modified regimen. These patients were older (P < 0.05), seven were j aundiced, and one had alcoholic liver cirrhosis. Hepatotoxicity was co nfirmed by challenge with pyrazinamide (n = 7), isoniazid (n = 6) and combined isoniazid/rifampicin (n = 1). No deaths were caused by hepato toxicity. Conclusion: In spite of an increase in AST levels to approxi mately 6 x ULN during antituberculosis treatment, the drugs can be con tinued or reintroduced in full in most cases. Risk factors of hepatoto xicity included old age, female sex and extensive tuberculosis, and no t alcohol consumption. Overall, hepatotoxicity during antituberculosis treatment can be monitored and managed easily.