Association between novel MRI-estimated pancreatic fat and liver histology-determined steatosis and fibrosis in non-alcoholic fatty liver disease

Abstract

Background: Ectopic fat deposition in the pancreas and its association with hepatic steatosis have not previously been examined in patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD).

Aim: To quantify pancreatic fat using a novel magnetic resonance imaging (MRI) technique and determine whether it is associated with hepatic steatosis and/or fibrosis in patients with NAFLD.

Methods: This is a cross-sectional study including 43 adult patients with biopsy-proven NAFLD who underwent clinical evaluation, biochemical testing and MRI. The liver biopsy assessment was performed using the NASH-CRN histological scoring system, and liver and pancreas fat quantification was performed using a novel, validated MRI biomarker; the proton density fat fraction.

Results: The average MRI-determined pancreatic fat in patients with NAFLD was 8.5% and did not vary significantly between head, body, and tail of the pancreas. MRI-determined pancreatic fat content increased significantly with increasing histology-determined hepatic steatosis grade; 4.6% in grade 1; 7.7% in grade 2; 13.0% in grade 3 (P = 0.004) respectively. Pancreatic fat content was lower in patients with histology-determined liver fibrosis than in those without fibrosis (11.2% in stage 0 fibrosis vs. 5.8% in stage 1-2 fibrosis, and 6.9% in stage 3-4 fibrosis, P = 0.013). Pancreatic fat did not correlate with age, body mass index or diabetes status.

Conclusions: In patients with NAFLD, increased pancreatic fat is associated with hepatic steatosis. However, liver fibrosis is inversely associated with pancreatic fat content. Further studies are needed to determine underlying mechanisms to understand if pancreatic steatosis affects progression of NAFLD.

Figure 1

Measurement of pancreatic fat using MRI PDFF. A single source image of a magnetic resonance image (MRI) gradient echo sequence of the abdomen is shown. Source image was obtained with a slice thickness of 8 mm. Regions of interest (ROIs) 100 mm² in area obtained in the head, body and tail of the pancreas are shown. For this patient, ROIs of the head, body and tail of the pancreas were obtained in three additional slices of the MRI sequence that are not shown. ROIs from this source image were propagated to registered locations on the corresponding PDFF maps to obtain fat fraction measurements.

Figure 2

MRI-determined pancreatic fat across regions of the pancreas. Mean magnetic resonance image (MRI) proton density fat-fraction (PDFF) is shown for the head, body and tail of the pancreas. Overall mean MRI PDFF was calculated as the mean of all regions of interest (ROIs) in the pancreas. Head, body and tail definitions are described in detail in the methods section. Paired two-tailed t-test showed no statistical difference in MRI PDFF between regions of the pancreas.

Figure 3

MRI-determined pancreatic and liver fat across histology-determined steatosis grade. Mean pancreas and liver fat percentage measured by magnetic resonance image (MRI) proton density fat-fraction (PDFF) are shown according to steatosis grade. Grade 1, grade 2 and grade 3 steatosis were determined using the NASH-CRN histological scoring system. Standard error bars are shown. T-test showed a significant difference between grade 1 and grade 3 steatosis in both pancreas MRI PDFF (P = 0.004) and liver MRI PDFF (P < 0.0001).

Figure 4

MRI-determined pancreatic fat across histology-determined fibrosis grade. Mean pancreas fat percentage measured by magnetic resonance image (MRI) proton density fat-fraction (PDFF) is shown according to fibrosis stage grouped by no fibrosis (stage 0), some fibrosis (stage 1a, 1b, or 2) and advanced fibrosis (stage 3 or 4). Fibrosis stage determined using the NASH-CRN histological scoring system. Standard error bars are shown. T-test showed a significant difference between no fibrosis and the presence of any degree of fibrosis (P = 0.013).