Cirrhosis with steatohepatitis after adjuvant tamoxifen

Altered expression of fatty acid–metabolizing enzymes in aromatase-deficient mice

“…These studies may further promote adjuvant tamoxifen, as 5-year treatment of tamoxifen for breast cancer undoubtedly outweighs the risks of the adverse effects. However, it was reported that rapidly progressive hepatic steatosis among nonobese nondiabetic breast cancer patients treated with tamoxifen was known to induce NASH and liver cirrhosis on rare occasions (8,(14)(15)(16)(17). The frequency of progressive hepatic steatosis had increased to 36% (18,19), and more than ten patients in our clinic were shown by liver biopsy to have tamoxifeninduced NASH.…”

“…However, evidence implying obesity is a risk for liver diseases has recently been accumulated. For example, liver cirrhosis is approximately sixfold more prevalent in obese individuals than in the general population, and obesity increases the risk of liver cirrhosis (7), and, in addition, gradual progression from hepatic steatosis to NASH and eventually to cirrhosis is supported by epidemiologic findings (8). Thus, a consensus about NASH was recently provided; namely, that hepatic steatosis is regarded as a risk of NASH and that a "second hit" capable of inducing necrosis, inflammation, and fibrosis in the liver is required for NASH, as most patients with hepatic steatosis do not develop liver cirrhosis (2,9,10).…”

Mechanisms of liver steatosis in rats with systemic carnitine deficiency due to treatment with trimethylhydraziniumpropionate

“…Several risk factors have been identified, among them ingestion of certain drugs (2)(3)(4)(5), alcohol abuse (6), viral hepatitis (7), diabetes (8), increased body weight (8,9), and intoxications (10). While impaired mitochondrial ␤ -oxidation is considered to be the principle cause for microvesicular steatosis (11), the mechanisms leading to macrovesicular steatosis have so far not been identified in detail.…”

Gender Difference in Alcoholic Liver Disease

“…Estrogen replacement reduces hepatic steatosis and restores the impairment in mitochondrial and peroxisomal fatty acid -oxidation to a wild-type level (Nemoto et al, 2000). In addition, tamoxifen is a well known antiestrogen used in the hormone treatment of estrogen receptor-positive breast cancer, and it has been shown to be associated with an increased risk of developing fatty liver and NASH in such patients (Oien et al, 1999;Van et al, 1996). Estrogens are potent endogenous antioxidant (Lacort et al, 1995;Yoshino et al, 1987), suppresses hepatic fibrosis in animal models, and attenuates induction of redox sensitive transcription factors, hepatocyte apoptosis and HSC activation by inhibiting the generation of ROS and TGF-in primary cultures (Itagaki et al, 2005;Lu et al, 2004;Shimizu et al, 1999;Yasuda et al, 1999;Zhou et al, 2001).…”