Unrecognized hepatic steatosis and non-alcoholic steatohepatitis in adjuvant tamoxifen for breast cancer patients

Adjuvant tamoxifen has become the treatment of choice against estrogen rece ptor-positive breast cancer. Adverse effects are rarely observed and since symptoms of hepatic steatosis, non-alcoholic steatohepatitis and cirrhosis are usually negligible, such effects are not well characterized despite lar ge cohort studies of adjuvant tamoxifen. This issue remains to be systemati cally studied. The present study consisted of 136 breast cancer patients tr eated with or without tamoxifen. Patients had laboratory tests once each mo nth and underwent abdominal computed tomography (CT) annually for 5 years. The extent of hepatic steatosis was assessed by CT as the liver/spleen rati o. While receiving adjuvant tamoxifen, 40 of 105 patients developed hepatic steatosis (liver/spleen ratio <0.9) without obvious changes in body mass i ndex. Twenty-one had a liver spleen ratio of <0.5, whereas none of the 31 p atients treated without tamoxifen had a ratio <0.9 or <0.5 (p<0.0001 and p< 0.0001, respectively). Hepatic steatosis was recognized in 35 of the 40 pat ients within the first 2 years of receiving adjuvant tamoxifen and 21 of th e 40 had increased transaminase levels. Liver biopsy revealed NASH in 6 of 7 patients among the 21 with a liver/spleen ratio of <0.5. A subset of indi viduals given adjuvant tamoxifen developed progressive hepatic steatosis wi thout significant changes in the body mass index. We suggest a liver/spleen ratio of <0.5 as a criterion upon which liver biopsy should be recommended since NASH frequently occurred in such patients.