Chest
Volume 99, Issue 2, February 1991, Pages 465-471
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Toxic Hepatitis with Isoniazid and Rifampin: A Meta-analysis

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INH-RELATED HEPATITIS; BRIEF HISTORY AND CLINICAL FEATURES

During the first few years after introduction of INH, only sporadic cases suggesting possible hepatotoxicity were noted, and jaundice developing in patients on treatment was often attributed to concurrent viral hepatitis or the toxic effects of other drugs such as PAS.2, 3, 4, 5, 6, 7 Berté and associates8 in 1959 stated that no case of hepatotoxicity was observed in 513 patients receiving INH, and such was its reputation for safety that in 1963 the American Thoracic Society recommended all

HEPATOTOXICITY ASSOCIATED WITH INH PLUS RMP

Soon after the introduction of RMP, several reports suggested that hepatitis was more frequent and severe in patients receiving both INH and RMP16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26 than in those receiving INH alone. Lesobre and associates16 described 12 cases of jaundice with four deaths among 50 patients receiving INH and RMP, although many of these had pre-existing liver disease. Lees et al17 observed four cases among 50 patients without known antecedent liver disease and stated that in

METHODS

A Medline search of the English language literature was performed. Articles published between 1966 and December, 1989 were searched using the MESH terms “tuberculosis/drug therapy,” “human” and either “isoniazid” or “rifampin.” In addition, “isoniazid” and “rifampin” were searched as text words. The search output included 1,496 potentially relevant citations. The selection was further restricted by choosing only those articles describing clinical trials or surveys of public health departments,

RESULTS

Studies with data on the incidence of toxic hepatitis in adults receiving anti-tuberculosis drugs were sorted according to drug regimen, as indicated in the Methods section. Table 1 lists data on the incidence of hepatitis in adults taking INH chemoprophylaxis, as well as in those taking multiple-drug INH regimens without RMP. Table 2 summarizes data in adults taking multiple-drug RMP regimens without INH, and Table 3 lists studies of adults taking INH plus RMP combination therapy. In Table 3,

DISCUSSION

The data presented above support the opinion that toxic hepatitis complicates TB chemotherapy with INH plus RMP more frequently than regimens including one but not both of these drugs. While this effect was especially striking in children, it was also noted in adults. Unfortunately, the adult data could not be further adjusted according to known risk factors for toxic hepatitis such as age,13,63 acetylator status,19,37,42,43,44 and alcohol use.13,15,42,63 Another potential methodologic problem

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