Isoniazid-associated hepatitis

Abstract

The pathogenesis, incidence and prevention of isoniazid-associated hepatitis are reviewed. The cause of this disorder has been attributed to acetylhydrazine, a metabolite of isoniazid. Studies done with animals have shown that acetylhydrazine can be converted to an acylating agent capable of producing hepatic necrosis. The onset of isoniazid-associated hepatitis may involve overt signs or symptoms of toxicity or it may be more insidious and revealed only by abnormal liver-function test results. The reported incidence of elevated SGOT levels associated with isoniazid therapy is approximately 20%. Usually, these elevations are transient, and they will return to normal without a change in therapy; however, the condition of some patients can progress to overt hepatic necrosis. The incidence of hepatitis associated with isoniazid rises with increasing age and in individuals who are regular or excessive consumers of alcohol. An increase in the risk of developing isoniazid-associated hepatitis with the concurrent use of rifampin has not been proven. There is indisputable evidence that isoniazid can be hepatotoxic. If serum transamine levels are determined to be three times the normal concentration, discontinuation of isoniazid therapy is recommended. The importance of regular monitoring for isoniazid-associated hepatitis is crucial to the prevention of severe liver disease and death.