A cholestatic liver chemistry profile (elevations in alkaline phosphatase and bilirubin) is commonly encountered in patients with hepatic venous outflow obstruction due to right heart failure. Liver biopsies from these patients demonstrate varying degrees of sinusoidal dilatation, red blood cell extravasation and sinusoidal congestion. Recently, a bile ductular reaction mimicking biliary tract disease has been identified in ∼ 50% of patients with venous outflow obstruction possibly explaining the cholestatic profile encountered in these patients. In this study, we evaluated the liver biopsies from 22 patients with heart failure. Marked sinusoidal dilatation involving zones 2 and 3 was observed in 15 patients. Similar to a previous study, 7 of 22 patients had histologic evidence of a mild ductular reaction. Cytokeratin 7 immunohistochemistry revealed a mild ductular reaction in an additional two cases. Strikingly, CK7 was aberrantly expressed in perivenular hepatocytes in 20 of 22 cases. Perivenular CK7 immunoreactivity was focal in most cases; however, in five cases it was quite extensive and extended into zone 2. There was no significant association between marked sinusoidal dilatation and extensive perivenular CK7 positivity. Extensive perivenular CK7 positivity was significantly associated with both elevated bilirubin, as well as the presence of fibrosis. However, a ductular reaction was not associated with a cholestatic liver chemistry profile.