This paper reviews hepatic toxicity during chemoprophylactic treatment with
isoniazid alone, and during the treatment or
retreatment of active
pulmonary tuberculosis with regimens containing one or more of the drugs
isoniazid,
rifampicin and
pyrazinamide.
Chemoprophylaxis with
isoniazid carries a risk of
drug-induced hepatitis, and this risk needs to be weighed against the advantages of preventing
tuberculosis morbidity. The risks of
hepatitis during standard treatment based on
isoniazid are very small, and most patients who develop
hepatitis recover. Moreover, it is often doubtful whether
hepatitis is in fact
drug-induced, and a proportion of patients who develop it already have
liver disease at the time treatment is started. The risks are acceptable in the treatment of bacteriologically active disease. There is no consistent evidence that giving
rifampicin with
isoniazid in the initial treatment of
tuberculosis increases the risk of
hepatitis; in particular, transient abnormalities in the results of tests of liver function during the early weeks of treatment do not imply serious toxicity; patients who are rapid acetylators of
isoniazid are not, as has been suggested, exposed to any special risk, and patients with known
liver disease can also be treated without undue risk.
Retreatment regimens based on
rifampicin plus
ethambutol carry a low risk of
hepatitis, even though patients who need retreating have often experience toxicity during their initial treatment. Frist-line or second-line regimens containing
pyrazinamide in currently accepted dosages, given daily or intermittently, carry a low and acceptable risk of hepatic toxicity. Finally, current studies of daily and intermittent short-course regimens based on
isoniazid,
rifampicin and
pyrazinamide will extend our knowledge of hepatic toxicity. Because such regimens involve small total quantitites of drugs given over short periods they are likely to give rise to less hepatic toxicity than regimens of standard duration.