Clinical

Liver tests best to gauge IBD medication hepatotoxicity

Last Updated: 2007-11-15 15:55:08 -0400 (Reuters Health)

By David Douglas

NEW YORK (Reuters Health) - The hepatotoxicity of 6-mercaptopurine (6-MP) and azathioprine treatment, seen in a minority of patients with irritable bowel disease (IBD), is most effectively monitored by means of liver tests rather than serum levels of the 6-MP metabolite, California-based researchers report in the November issue of the American Journal of Gastroenterology.

As senior investigator Dr. Tram T. Tran told Reuters Health, "In adults treated with 6-MP or azathioprine, we shouldn't limit the use of these medications based only on metabolite levels but based on a given individual's liver profile and monitoring."

Dr. Tran of Cedars Sinai Medical Center, Los Angeles and colleagues note that in pediatric patients with IBD treated with 6-MP, about 10% to 15% show hepatotoxicity, which is associated with elevated levels of the 6-MP metabolite 6-methylmercaptopurine ribonucleotide (6-MMPR).

To evaluate the situation in adults, the researchers studied 173 such patients. Hepatoxicity was defined as more than twice normal levels of the aminotransferases AST or ALT, or cholestasis.

Eight patients (8.6%) met these criteria. Their mean 6-MMPR level was significantly greater than in those without hepatotoxicity. Overall, patients with the highest 6-MMPR levels were at 5-times greater risk than those with lower levels.

Nevertheless, elevated 6-MMPR levels were not definitive. Nearly 90% of patients with such levels had no hepatotoxicity, while almost 40% of patients with 6-MMPR levels below the cut-off point did have hepatotoxicity.

Thus the researchers conclude that "dose reduction or cessation of 6-MP/azathioprine, even with high 6-MMPR levels, should be reserved for patients with elevated aminotransferases."

Am J Gastroenterol 2007;102:2488-2494.