Detection of Reduction in Liver Stiffness as a Result of Weight Loss Surgery using MR Elastography
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/m2, BMI at 6 months after surgery=33.5±5.4 kg/m2) 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

1. Dixon JB, Bhathal PS, Hughes NR, and O'Brien PE. Nonalcoholic fatty liver disease: Improvement in liver histological analysis with weight loss. Hepatology, 2004;39:1647–1654.

2. Hines CDG, Agni R, Roen C, et al. Validation of MRI biomarkers of hepatic steatosis in the presence of iron overload in the ob/ob mouse. J. Magn. Reson. Imaging, 2012;35:844–851.

3. Yin M, Talwalkar JA, Glaser KJ, et al. Assessment of Hepatic Fibrosis With Magnetic Resonance Elastography. Clin. Gastroenterol Hepatol. 2007;5:1207-1213.

4. Talwalkar JA, Yin M, Fidler JL, et al. Magnetic resonance imaging of hepatic fibrosis: emerging clinical applications. Hepatology. 2008;47:332–342.

5. Kleiner, DE, Brunt, EM, Van Natta, M, et al. J. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology, 2005;41:1313–1321.

Figures

Figure 1: The stiffness of the liver of a patient with biopsy confirmed advanced fibrosis decreased 6 months after surgery. Stiffness dropped from 5.9kPa at time of surgery to 4.5kPa 6 months later.

Figure 2: A larger reduction in liver stiffness was observed in patients with liver fibrosis (red) than patients without liver fibrosis (blue).

Table 1: A statistical significant larger decrease in stiffness was observed in patients with fibrosis than patients without fibrosis. No such differences were observed in patients with or without inflammation, with or without steatosis, or with or without suspicious or definite NASH.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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