Curtis N. Wiens1, Alan B. McMillan1, Nathan S. Artz1,2, Rashmi Agni3, Michael Peterson4, Nikolaus Szeverenyi5, William Haufe5, Catherine Hooker5, Luke Funk6, Jacob Greenberg6, Guilherme M. Campos7, Santiago Horgan8, Garth Jacobsen8, Tanya Wolfson9, Claude Sirlin5, and Scott B. Reeder1,10,11,12,13
1Radiology, University of Wisconsin, Madison, WI, United States, 2Diagnostic Imaging, St. Jude Children's Research Hospital, Memphis, TN, United States, 3Pathology, University of Wisconsin, Madison, WI, United States, 4Tacoma General Pathology, Tacoma, WA, United States, 5Radiology, University of California, San Diego, CA, United States, 6Surgery, University of Wisconsin, Madison, WI, United States, 7Virginia Commonwealth University, Surgery, VA, United States, 8Surgery, University of California, San Diego, CA, United States, 9Computational and Applied Statistics Laboratory, University of California, San Diego, CA, United States, 10Medical Physics, University of Wisconsin, Madison, WI, United States, 11Biomedical Engineering, University of Wisconsin, Madison, WI, United States, 12Medicine, University of Wisconsin, Madison, WI, United States, 13Emergency Medicine, University of Wisconsin, Madison, WI, United States
Synopsis
This study tracked changes in liver stiffness in morbidly obese
patients undergoing bariatric surgery. 22 patients undergoing bariatric surgery
were recruited for MRI studies including MR elastography (MRE) at 2 time points:
1-2 days
prior to and 6 months
after bariatric surgery. Changes in liver stiffness as measured
by MRE were compared to intraoperative biopsies which were performed to assess
relevant histological features (steatosis, inflammation and fibrosis) and their
relation to liver stiffness. Follow-up measurement of liver stiffness 6 months after bariatric
surgery showed statistically significant reductions in liver stiffness. Patients with biopsy confirmed liver fibrosis,
inflammation and features of NASH exhibited the largest reductions in liver
stiffness. Introduction
The rising incidence
of obesity and metabolic syndrome has led to a dramatic increase in
non-alcoholic fatty liver disease (NAFLD).
NALFD is characterized initially by isolated hepatic steatosis which in
some patients progresses to steatohepatitis (NASH) and eventually cirrhosis. Reductions
in steatosis, fibrosis, and inflammation have been observed histologically as a
result of weight loss surgery (WLS), indicating treatment response (1). Non-invasive biomarkers that track treatment
response are desirable, specifically steatosis using quantitative water-fat
imaging (2) as well as fibrosis and inflammation with MR elastography (3,4).
The
purpose of this study was to measure liver stiffness reduction after WLS
to determine which histological features were predictive of a larger decrease
in liver stiffness.
Methods
Patients undergoing WLS (vertical gastrectomy or Roux-en-Y gastric
bypass) were recruited at the University of California – San Diego and the
University of Wisconsin – Madison for IRB-approved MRI studies at 2 times
points: 1-2 days
prior to surgery and approximately
6 months after surgery. All imaging was performed at either 1.5T or 3T systems
(Signa HDxt and MR750, GE Healthcare, Waukesha. WI).
At both time points, 2D GRE MRE was performed (1.5T/3T): TR=50ms, TE=22/19ms,
in-plane resolution range= 1.9x3.1mm – 3.8x5.0mm, slice thickness=5-10cm, shear
wave frequency=60Hz. In addition, chemical
shift encoded fat quantification was performed (1.5T/3T): 6 echoes, TR=13.4/8.6ms, ΔTE=2.0/1.0ms, flip angle=5°/3°, resolution=1.7x2.8x8 /1.7x3.4x8mm.
Intraoperative biopsies were assessed by two experienced
pathologists for steatosis, inflammation and fibrosis using the NASH CRN
histologic scoring system (5). For each histological feature, the staging score
was reduced to either a feature present or feature absent classification. Patients with stage 0 fibrosis, grade 0
steatosis and grade 0 or 1 NASH CRN were classified as feature absent. Similarly, patients with fibrosis stage ≥ 1, steatosis
grade ≥ 1, and NASH CRN grade ≥ 2 were classified
as feature present.
Wilcoxon rank sum tests were performed to test for statistical
difference in stiffness changes between histologically defined subgroups:
fibrosis, inflammation, steatosis, suspicious or definite NASH. Spearman’s correlations were used to assess
relations between changes in stiffness with changes in proton density fat fraction
(PDFF) and body mass index (BMI).
Results
22
patients were successfully recruited (17 females, 5 males, age = 46.3±10.1 years, BMI at surgery= 41.8±6.1 kg/m
2, BMI at 6 months after surgery=33.5±5.4 kg/m
2) There was a significant overall reduction
in liver stiffness (Figure 1) 6 months after WLS (2.95±1.03 kPa, 2.58±0.72 kPa, p-value = 0.04 ). The reduction in stiffness for patients with
fibrosis was significantly greater than for patients without fibrosis (Figure 2). No statistical difference was observed in
patients with inflammation, steatosis, or suspicious or definite NASH (Table 1). Additionally, no significant correlations between
changes in stiffness with changes in PDFF (r=-0.06, p-value=0.7779) or BMI (r=0.29, p-value=0.1892)
were found.
Discussion and Conclusions
Repeated
measurements of liver stiffness immediately prior to and 6 months after WLS showed
significant reductions in liver stiffness, especially in patients with baseline
fibrosis. These findings suggest that
weight loss and WLS led to improvement in hepatic fibrosis, although future
research with end-of-treatment biopsies are needed for confirmation. If validated by such research, our results
support the use of MRE as a non-invasive biomarker to monitor hepatic treatment
response after weight loss surgery.
Acknowledgements
We acknowledge support from NSERC, NIH (R01 DK083380, R01
DK088925) and GE Healthcare.References
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