Clinical

Glucose intolerance predicts tamoxifen-induced hepatotoxicity

Last Updated: 2004-07-05 11:45:02 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Glucose intolerance seems to predict tamoxifen-induced hepatotoxicity in breast cancer patients with preexisting liver steatosis, according to a report in the June European Journal of Gastroenterology and Hepatology.

More than 30% of breast cancer patients who receive adjuvant tamoxifen treatment develop nonalcoholic fatty liver disease, the authors explain, but tamoxifen's hepatotoxic effects have not been investigated in large studies.

Dr. Ioannis S. Elefsiniotis from Hippokration Hospital, Athens, Greece and colleagues investigated predisposing factors for nonalcoholic fatty liver disease in patients with breast cancer patients who were treated with adjuvant tamoxifen therapy.

Of 60 patients, 26 (43.3%) had tamoxifen-induced hepatotoxicity and 34 (56.7%) did not, the authors report. Age, duration of treatment, percentage of premenopausal women, and baseline liver function test results were comparable between the two groups.

Body-mass index, baseline fasting glucose, and cholesterol and triglyceride levels were significantly higher in women who developed tamoxifen-induced hepatotoxicity than in women who did not, the report indicates.

Women with impaired glucose tolerance at baseline were nearly 2.5 times as likely as women without IGT to exhibit tamoxifen-induced hepatotoxicity, the researchers note. Glucose intolerance predicted tamoxifen-induced hepatotoxicity even after matching for body-mass index.

Six of 9 patients with tamoxifen-induced hepatotoxicity who underwent liver biopsy had mild to moderate steatosis, two had cirrhosis with ongoing liver inflammation, and one had macrovesicular liver steatosis, the investigators report. All nine women had impaired glucose tolerance before receiving tamoxifen.

Liver function tests normalized within 6 months in all 18 patients with tamoxifen-induced hepatotoxicity who discontinued tamoxifen treatment, the results indicate.

"Tamoxifen-induced hepatotoxicity is observed in a great proportion of breast cancer patients with preexisting liver steatosis, especially those with higher body mass index and higher glucose and lipid levels at baseline control," the authors conclude. "Glucose intolerance before the beginning of tamoxifen treatment seems to be a predictor of the hepatotoxicity of the drug, unrelated to baseline body-mass index, a finding that needs further investigation."

Eur J Gastroenterol Hepatol 2004;16:593-598.