Non-cirrhotic hepatocellular carcinoma during Crohn’s disease therapy with azathioprine : possible involvement of focal hepatocyte glycogenosis in hepatocarcinogenesis

Hepatocellular carcinoma (HCC) rarely develops in patients with Crohn's disease (CD) without cirrhosis. Focal hepatic glycogenosis (FHG), characterized by localized hepatocellular glycogen accumulation, has been proposed as a potential preneoplastic lesion, particularly in the setting of long-term azathioprine (AZA) therapy. We report two non-cirrhotic CD patients who developed HCC during prolonged AZA treatment; both exhibited FHG in their background livers. A review of the literature identified only 13 previously reported HCC cases in CD patients, most of which were associated with AZA use or FHG. These findings suggest a possible link between CD, AZA therapy, FHG, and hepatocarcinogenesis. Long-term AZA therapy in CD may be involved in the development of FHG and may contribute to HCC development, even in non-cirrhotic livers, underscoring the need for careful liver surveillance in CD patients receiving prolonged AZA treatment.