Does Farnesoid X receptor (FXR) Have a Role in NAFLD Progression ?

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is the emerging cause of chronic liver disease. In addition, steatosis may lead to failure of obtaining sustained virological response after hepatitis C virus eradication. Therefore, there is a trend to identify effective strategies for managing hepatic steatosis. Farnesoid X receptor (FXR) agonists are reported to play a role in NAFLD treatment. Objective: This study aimed to explore the immunohistochemical expression of FXR in NAFLD spectrum in association with the clinicopathological data. Material and method: This was a retrospective study including 50 cases of NAFLD and 23 cases of normal liver. The NAFLD group was subdivided into 11 cases of NAFL (simple steatosis) and 39 cases of non-alcoholic steatohepatitis (NASH). Results: Hepatocyte FXR nuclear expression was significantly decreased in NASH group (P=0.001) with no significant decrease in NAFL group compared to normal liver (P=0.149). Bile duct FXR expression was significantly lower in NAFL group compared to normal liver (P= 0.009) to reach the lowest level in NASH group (P= 0.017). In NAFLD group, there was an inverse correlation between hepatocyte FXR nuclear expression and the ALT/AST ratio (r=-0.349 and P=0.013). However, hepatocyte FXR nuclear expression was significantly associated with moderate grade of steatosis and severe fibrosis (P= 0.044 and P= 0.033, respectively). Conclusion: Hepatocyte FXR nuclear expression showed a stepwise decrease in its expression from normal to NASH passing with NAFL. Therefore, FXR has a protective role against NAFLD progression. Elevated liver enzymes could be used as a non-invasive method for monitoring FXR agonists' efficacy.