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Super paramagnetic iron oxide MRI shows defective Kupffer cell uptake function in non-alcoholic fatty liver disease
  1. Taketoshi Asanuma1,2,
  2. Masafumi Ono3,
  3. Kei Kubota4,
  4. Akira Hirose3,
  5. Yoshihiro Hayashi5,
  6. Toshiji Saibara3,
  7. Osamu Inanami1,
  8. Yasuhiro Ogawa4,
  9. Hideaki Enzan5,
  10. Saburo Onishi3,
  11. Mikinori Kuwabara1,
  12. Jude A Oben6,7
  1. 1Department of Radiology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
  2. 2Department of Veterinary Sciences, University of Miyazaki, Miyazaki, Japan
  3. 3Department of Gastroenterology and Hepatology, Kochi Medical School, Nankoku, Kochi, Japan
  4. 4Department of Radiology, Kochi Medical School, Nankoku, Kochi, Japan
  5. 5Department of Pathology, Kochi Medical School, Nankoku, Kochi, Japan
  6. 6Centre for Hepatology, University College London, UK
  7. 7Guy's and St. Thomas' Hospital, London, UK
  1. Correspondence to Masafumi Ono, Department of Gastroenterology and Hepatology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan; nom{at}


Background The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is incompletely understood. Kupffer cells (KCs), 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 comparative technology dependent on KC phagocytic function.

Objective 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 controls with chronic hepatitis C. SPIO-MRI was then performed in all patients. Normal rats fed a methionine-choline-deficient 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 KCs in patients and rat livers.

Results Relative signal enhancement (RSE), inversely proportional to KC function, was higher in patients with NAFLD than in 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 patients with NAFLD and experimental animals with NASH, worsens with the degree of steatosis and is not due to a reduction of KC numbers.

  • Kupffer cells
  • phagocytosis
  • non-alcoholic steatohepatitis
  • super-paramagnetic iron oxide-MRI
  • non-alcoholic fatty liver disease
  • KCs
  • Kupffer cells
  • RSE
  • relative signal enhancement
  • NASH
  • non-alcoholic steatohepatitis
  • MCD
  • methionine-choline-deficient diets
  • CH-C
  • chronic hepatitis C
  • NAS
  • NAFLD activity score

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  • Supplementary figures are published online only at

  • Funding Grants-in-Aid for Scientific Research (C) 2006 Grant # 17590656, The Ministry of Education, Science, Sports and Culture, Japan; Wellcome Trust, UK (JAO).

  • Competing interests None.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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