Background: The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is incompletely understood. Kupffer cells (KC), phagocytic liver-resident macrophages, provide a protective barrier against egress of endotoxin from the portal to the systemic circulation. It is not known if KC phagocytic function is impaired in NAFLD. Super-paramagnetic Iron Oxide (SPIO) magnetic resonance imaging is a comparatively technology dependent on KC phagocytic function. The aim of the present study was to evaluate KC uptake function, in patients and experimental animals with NAFLD, using SPIO.
Methods: Abdominal CT and histological examination of liver biopsy specimens were used to estimate the degree of steatosis in patients with NAFLD and chronic hepatitis C controls. SPIO-MRI was then performed in all patients. Normal rats fed a methionine-choline deficient (MCD) diet to induce non-alcoholic steatohepatitis (NASH), the more severe stage of NAFLD, and obese, insulin resistant, Zucker fa/fa rats with steatohepatitis, were also studied with SPIO-MRI and analysed for hepatic uptake of fluorescent microbeads. Immunohistochemical analysis evaluated the numbers of KC in patients and rat livers.
Results: Relative signal enhancement (RSE), inversely proportional to KC function, was higher in patients with NAFLD compared to controls and with the degree of steatosis on CT. RSE also positively correlated with the degree of steatosis on histology and was similarly higher in rats with induced severe NAFLD (NASH). On immunohistochemistry defective phagocytic function was the result of reduced phagocytic uptake and not due to reduced KC numbers in rats or patients with NAFLD. Conclusions: KC uptake function is significantly impaired in NAFLD patients and experimental animals with NASH, worsens with the degree of steatosis and is not due to a reduction of KC numbers.