Teaching Case

A 54-year-old female veteran with a history of right-sided breast cancer underwent modified radical right-sided mastectomy. She was on venlafaxine for depression. Few months after starting Tamoxifen she presented with elevated liver enzymes. She denies a history of dyslipidemia, diabetes mellitus, or herbal, over the counter medications, or alcohol use.

CT abdomen with liver measuring 21 HU (Hounsfield Units) consistent with diffuse severe steatosis(figure 1 and 2).
Two years after stopping Tamoxifen, CT imaging showed complete reversibility of steatosis(figure 2).

A)Background:
Tamoxifen is an estrogen-receptor antagonist, the most commonly used adjuvant treatment in management of breast cancer. It has a statistically significant influence on hepatic fat content and is associated with frequent development of hepatic steatosis[1].

B)Clinical Perspective:
Drug induced steatosis largely remains asymptomatic and may present with fatigue, abdominal pain, weakness or loss of appetite. Drugs commonly associated with hepatic steatosis are aspirin, valproate, NSAID, tetracycline, glucocorticoids, amiodarone with some of the proposed mechanisms being arrested beta oxidation, inhibition of ATP synthesis and arrested ETC(Electron Transport Chain) or indirectly through promotion of weight gain and glucose intolerance[2].

C)Imaging Perspective:
Ultrasound is the most common modality of investigation for fatty liver and is evaluated based on its echogenicity in comparison with that of spleen and the renal cortex[3]. It is limited due to its operator dependence and inability to detect mild steatosis.
With contrast-enhanced CT, a difference between liver and spleen attenuation has a sensitivity of 93%, a specificity of 93%, and a receiver operating curve of 0.98[4].
MRI is in use since two decades to detect fatty liver with utilization of in-phase and opposed-phase images. These images are similar in normal liver, with loss on opposed-phase signal in fatty liver[5].
MR Spectroscopy is by far the most accurate imaging modality for fatty liver.
Diffuse severe steatosis of liver was seen on CT abdominal imaging(figure 1 and 2) in our patient and two years after stopping Tamoxifen, liver showed complete reversibility of steatosis(figure 3).
Liver biopsy is the most definitive diagnostic tool.

D)Outcome:
Our case shows dramatic improvement in the appearance of the liver and normalization of her liver enzymes after discontinuation of tamoxifen.
It is found that tamoxifen has a strong influence on hepatic fat content and is strongly associated with frequent development and rapid reversal of hepatic steatosis in patients with breast cancer after stopping the medication. Annual CT studies are useful for detecting and monitoring the clinical course of tamoxifen-induced hepatic steatosis[1].

E)Teaching Points:
The importance of screening lies in the fact that most of the patients remain asymptomatic despite steatosis.
Radiologists should be able to differentiate steatosis from metastasis in postoperative patients with breast cancer, as focal fat deposition may resemble localized mass[1].It can be differentiated based on fat content, location, no mass effect, margins, geographic configuration of the lesion, and no contrast enhancement[5].
Primary care physicians and other specialties should be aware of the transient characteristics of tamoxifen induced steatosis before deciding on further investigations and liver biopsy.

Written informed patient consent for publication has been obtained.