A cohort of 82 patients who underwent PD at Okayama University Hospital between 2003 and 2009 was enrolled and the clinicopathological features were compared between patients with and without
NAFLD after PD. Computed tomography (CT) images were evaluated every 6 mo after PD for follow-up. Hepatic steatosis was diagnosed on CT when hepatic attenuation values were 40 Hounsfield units. Liver biopsy was performed for 4 of 30 patients with
NAFLD after PD who consented to undergo biopsies. To compare
NAFLD after PD with
NAFLD associated with
metabolic syndrome, liver samples were obtained from 10 patients with
NAFLD associated with
metabolic syndrome [
fatty liver, n = 5; non-
alcoholic steatohepatitis (NASH), n = 5] by percutaneous ultrasonography-guided liver biopsy. Double-fluorescence immunohistochemistry was applied to examine CD14 expression as a marker of
lipopolysaccharide (LPS)-sensitized macrophage cells (Kupffer cells) in liver biopsy specimens.
RESULTS: The incidence of postoperative
NAFLD was 36.6% (30/82). Univariate analysis identified
cancer of the pancreatic head, sex, diameter of the main pancreatic duct, and dissection of the nerve plexus as factors associated with the development of
NAFLD after PD. Those patients who developed
NAFLD after PD demonstrated significantly decreased levels of
serum albumin, total
protein,
cholesterol and
triglycerides compared to patients without
NAFLD after PD, but no
glucose intolerance or
insulin resistance. Liver biopsy was performed in four patients with
NAFLD after PD. All four patients showed moderate-to-severe steatosis and NASH was diagnosed in two. Numbers of cells positive for CD68 (a marker of Kupffer cells) and CD14 (a marker of LPS-sensitized Kupffer cells) were counted in all biopsy specimens. The number of CD68+ cells in specimens of
NAFLD after PD was significantly increased from that in specimens of
NAFLD associated with
metabolic syndrome specimens, which indicated the presence of significantly more Kupffer cells in
NAFLD after PD than in
NAFLD associated with
metabolic syndrome. Similarly, more CD14+ cells, namely, LPS-sensitized Kupffer cells, were observed in
NAFLD after PD than in
NAFLD associated with
metabolic syndrome. Regarding NASH, more CD68+ cells and CD14+ cells were observed in NASH after PD specimens than in NASH associated with
metabolic syndrome. This showed that more Kupffer cells and more LPS-sensitized Kupffer cells were present in NASH after PD than in NASH associated with
metabolic syndrome. These observations suggest that after PD, Kupffer cells and LPS-sensitized Kupffer cells were significantly upregulated, not only in NASH, but also in simple
fatty liver.
CONCLUSION:
NAFLD after PD is characterized by both
malnutrition and the up-regulation of CD14 on Kupffer cells. Gut-derived
endotoxin appears central to the development of
NAFLD after PD.