CD14 expression and Kupffer cell dysfunction in non‐alcoholic steatohepatitis: Superparamagnetic iron oxide‐magnetic resonance image and pathologic correlation

Abstract

Kupffer cell (KC) function and CD14 expression contributes to pathogenesis of non-alcoholic steatohepatitis (NASH). However, these relationships remain unclear. We investigated the relationship of KC function with superparamagnetic iron oxide-enhanced magnetic resonance imaging (SPIO-MRI), histopathological severity of NASH, and number of CD14-positive KCs in NASH. This retrospective study included 32 patients (24 with NASH and eight with simple steatosis) who had previously undergone SPIO-MRI with T2-weighted gradient-recalled echo sequence. All subjects were diagnosed pathologically and were evaluated for necroinflammation grade, fibrosis stage, and number of CD14-positive KCs. Patients with NASH and simple steatosis were compared by using the Mann-Whitney test to determine differences in percent reduction of liver-to-muscle signal intensity ratio (reduction-%LMR), as a surrogate parameter of KC function, and number of CD14-positive KCs. Kruskal-Wallis test and Pearson's correlation coefficient were used to analyze relation among reduction-%LMR, histopathological severity and number of CD14-positive KCs. There were statistically significant differences in reduction-%LMR and number of CD14-positive KCs between NASH and simple steatosis patients (Mann-Whitney test, P < 0.001 for all comparisons). Reduction-%LMR decreased with an increase in necroinflammation grade or fibrosis stage. The number of CD14-positive KCs increased with an increase in necroinflammation grade and fibrosis stage (Kruskal-Wallis test, both, P < 0.001). A high correlation was seen between number of CD14-positive KCs and reduction-%LMR (Pearson r = 0.81; P < 0.001). KC phagocytic function evaluated with SPIO-MRI correlated with histopathological severity and number of CD14-positive KCs. These results support the concept that KC phagocytic dysfunction contributes to the pathogenesis of NASH.