Loss of estrogen receptor-alpha (ER-alpha) in the liver is associated with hepatic steatosis and inflammation. We conducted a study in order to investigate the presence and extent of ER-alpha expression in NASH, and its relationship with histological findings. Fifty-four patients with histologically confirmed NASH, 12 patients with simple steatosis (SS), and 6 patients with normal liver tissue (NLT) were included. NASH activity score and fibrosis score were calculated according to biopsy findings. Liver biopsy specimens were immunohistochemically stained for ER-alpha expression. Nuclear ER-alpha expression percentage (staining index) was calculated. Mean staining index was significantly different across the NASH, SS, and NLT groups (6.3 +/- 9.9 vs. 22.1 +/- 26.4 vs. 44.2 +/- 24.8, respectively, p < 0.001 for all comparisons). Staining index was significantly higher in women than in men (19.4 +/- 22.2 vs. 7.9 +/- 15.3, respectively, p = 0.003). Staining index negatively correlated with serum ALT (r=-0.240; p = 0.04), fasting plasma glucose (r=-0.261; p = 0.027), and fibrosis score (r=-0312; p = 0.011). As a conclusion, hepatic nuclear ER-alpha expression percentage (staining index) is lower in patients with NASH when compared to SS and NLT groups. Staining index is negatively correlated with serum ALT levels, plasma glucose, and fibrosis score. Further studies are required to clarify the significance of ER-alpha expression in NASH. (C) 2013 Elsevier GmbH. All rights reserved.