Pratt and associates [1] reported the first case of tamoxifen-induced nonalcoholic steatohepatitis, emphasizing the importance of this diagnosis and the possibility of progression to cirrhosis.

A 72-year-old woman had right mastectomy for breast cancer. Results of liver function tests and ultrasonography of the liver done before surgery were normal. She began receiving tamoxifen, 20 mg/d, after surgery. Her medical history was unremarkable. She consumed no alcohol and had no risk factors for the acquisition of viral hepatitis. Seven months after surgery, the patient had an alanine aminotransferase level of 35 IU/L (normal less than 25 IU/L) and an aspartate aminotransferase level of 36 IU/L (normal less than 21 IU/L). During the next 16 months, liver enzyme levels remained mildly elevated. Thereafter, a new biochemical work-up showed not only persistently elevated aminotransferase levels but also thrombocytopenia (platelet count, 125 x 10³/mm³; normal, 150 to 300 x 10³/mm³) and decreased prothrombin time (63%; normal, 70% to 100%). An ultrasonogram of the upper abdomen showed repermeabilization of the umbilic vein, and esophageal varices were discovered during endoscopy. Until that time, tamoxifen was the only drug given to the patient. Results of serologic tests for hepatitis, iron studies, and tests for antimitochondrial and anti-smooth-muscle antibodies were normal or negative. Examination of a percutaneous liver biopsy specimen showed diffuse macrovacuolar steatosis, lobular inflammation, Mallory bodies, extensive fibrosis, and micronodular cirrhosis (Figure 1).

View larger version (146K): [in this window] [in a new window]   Figure 1. Percutaneous liver biopsy specimen showing macrovesicular steatosis, lobular inflammation, and extensive fibrosis. (Hematoxylin-eosin stain. Original magnification x 175.).

These histologic features, characteristic of nonalcoholic steatohepatitis, are indistinguishable from those of alcohol-induced liver disease [2]. The absence of alcohol consumption is thus the cornerstone of this diagnosis. Predisposing factors for the disease include obesity, diabetes, hyperlipidemia, and female sex [3, 4]. However, such factors are not always present, and several drugs have been associated with nonalcoholic steatohepatitis.

Liver function tests should thus be regularly done during tamoxifen treatment, and, in the case of prolonged and unexplained elevations of aminotransferase levels, liver biopsy must be done.