Magnetic Resonance Elastography Predicts Advanced Fibrosis in Patients With Nonalcoholic Fatty Liver Disease: A Prospective Study

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Abstract

Retrospective studies have shown that two-dimensional magnetic resonance elastography (2D-MRE), a novel MR method for assessment of liver stiffness, correlates with advanced fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). Prospective data on diagnostic accuracy of 2D-MRE in the detection of advanced fibrosis in NAFLD are needed. The aim of this study is to prospectively assess the diagnostic accuracy of 2D-MRE, a noninvasive imaging biomarker, in predicting advanced fibrosis (stage 3 or 4) in well-characterized patients with biopsy-proven NAFLD. This is a cross-sectional analysis of a prospective study including 117 consecutive patients (56% women) with biopsy-proven NAFLD who underwent a standardized research visit: history, exam, liver biopsy assessment (using the nonalcoholic steatohepatitis Clinical Research Network histological scoring system), and 2D-MRE from 2011 to 2013. The radiologist and pathologist were blinded to clinical and pathology/imaging data, respectively. Receiver operating characteristics (ROCs) were examined to assess the diagnostic test performance of 2D-MRE in predicting advanced fibrosis. The mean (± standard deviation) of age and body mass index was 50.1 (± 13.4) years and 32.4 (± 5.0) kg/m ², respectively. The median time interval between biopsy and 2D-MRE was 45 days (interquartile range: 50 days). The number of patients with fibrosis stages 0, 1, 2, 3, and 4 was 43, 39, 13, 12, and 10, respectively. The area under the ROC curve for 2D-MRE discriminating advanced fibrosis (stage 3-4) from stage 0-2 fibrosis was 0.924 ( P < 0.0001). A threshold of >3.63 kPa had a sensitivity of 0.86 (95% confidence interval [CI]: 0.65-0.97), specificity of 0.91 (95% CI: 0.83-0.96), positive predictive value of 0.68 (95% CI: 0.48-0.84), and negative predictive value of 0.97 (95% CI: 0.91-0.99). Conclusions: MRE is accurate in predicting advanced fibrosis and may be utilized for noninvasive diagnosis of advanced fibrosis in patients with NAFLD. (H epatology 2014;60:1920–1928)

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Most cited references 27

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Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis.

P Angulo, J Keach, K P Batts … (1999)

Nonalcoholic steatohepatitis (NASH) may present with increased hepatic fibrosis progressing to end-stage liver disease. No factors that determine increasing fibrosis and histologically advanced disease have been recognized, thus, liver biopsy is recommended in all patients for diagnosis and prognosis. Our aim was to identify independent predictors of severe hepatic fibrosis in patients with NASH. One hundred and forty-four patients were studied. All patients underwent liver biopsy. Clinical and biochemical variables were examined with univariate and multivariate analysis. Thirty-seven (26%) patients had no abnormal fibrosis, 53 (37%) had mild fibrosis, 15 (10%) had moderate fibrosis, 14 (10%) had bridging fibrosis, and 25 (17%) had cirrhosis. In multivariate analysis, older age (P =. 001), obesity (P =.002), diabetes mellitus (P =.009), and aspartate transaminase/alanine transaminase (AST/ALT) ratio greater than 1 (P =.03) were significant predictors of severe liver fibrosis (bridging/cirrhosis). Body mass index (P =.003) was the only independent predictor of the degree of fat infiltration. Increased transferrin saturation correlated positively with the severity of fibrosis (P =.02) in univariate analysis, and there was a trend for more female patients among those with more advanced fibrosis (P =. 09). However, iron studies or gender were not significant when controlled for age, obesity, diabetes, and AST/ALT ratio. In conclusion, older age, obesity, and presence of diabetes mellitus help identify those NASH patients who might have severe liver fibrosis. This is the subgroup of patients with NASH who would be expected to derive the most benefit from having a liver biopsy and considering investigational therapies.

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The natural history of nonalcoholic fatty liver disease: a population-based cohort study.

Joseph Adams, Paul Angulo, Raymond St. Leger … (2005)

The natural history of nonalcoholic fatty liver disease (NAFLD) in the community remains unknown. We sought to determine survival and liver-related morbidity among community-based NAFLD patients. Four hundred twenty patients diagnosed with NAFLD in Olmsted County, Minnesota, between 1980 and 2000 were identified using the resources of the Rochester Epidemiology Project. Medical records were reviewed to confirm diagnosis and determine outcomes up to 2003. Overall survival was compared with the general Minnesota population of the same age and sex. Mean (SD) age at diagnosis was 49 (15) years; 231 (49%) were male. Mean follow-up was 7.6 (4.0) years (range, 0.1-23.5) culminating in 3192 person-years follow-up. Overall, 53 of 420 (12.6%) patients died. Survival was lower than the expected survival for the general population (standardized mortality ratio, 1.34; 95% CI, 1.003-1.76; P = .03). Higher mortality was associated with age (hazard ratio per decade, 2.2; 95% CI, 1.7-2.7), impaired fasting glucose (hazard ratio, 2.6; 95% CI, 1.3-5.2), and cirrhosis (hazard ratio, 3.1, 95% CI, 1.2-7.8). Liver disease was the third leading cause of death (as compared with the thirteenth leading cause of death in the general Minnesota population), occurring in 7 (1.7%) subjects. Twenty-one (5%) patients were diagnosed with cirrhosis, and 13 (3.1%) developed liver-related complications, including 1 requiring transplantation and 2 developing hepatocellular carcinoma. Mortality among community-diagnosed NAFLD patients is higher than the general population and is associated with older age, impaired fasting glucose, and cirrhosis. Liver-related death is a leading cause of mortality, although the absolute risk is low.

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Magnetic resonance elastography of liver: technique, analysis, and clinical applications.

Sudhakar K. Venkatesh, Meng Yin, Richard L. Ehman (2013)

Many pathological processes cause marked changes in the mechanical properties of tissue. MR elastography (MRE) is a noninvasive MRI based technique for quantitatively assessing the mechanical properties of tissues in vivo. MRE is performed by using a vibration source to generate low frequency mechanical waves in tissue, imaging the propagating waves using a phase contrast MRI technique, and then processing the wave information to generate quantitative images showing mechanical properties such as tissue stiffness. Since its first description in 1995, published studies have explored many potential clinical applications including brain, thyroid, lung, heart, breast, and skeletal muscle imaging. However, the best-documented application to emerge has been the use of MRE to assess liver disease. Multiple studies have demonstrated that there is a strong correlation between MRE-measured hepatic stiffness and the stage of fibrosis at histology. The emerging literature indicates that MRE can serve as a safer, less expensive, and potentially more accurate alternative to invasive liver biopsy which is currently the gold standard for diagnosis and staging of liver fibrosis. This review describes the basic principles, technique of performing a liver MRE, analysis and calculation of stiffness, clinical applications, limitations, and potential future applications. Copyright © 2012 Wiley Periodicals, Inc.

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Author and article information

Journal

Journal ID (nlm-ta): Hepatology

Journal ID (iso-abbrev): Hepatology

Journal ID (publisher-id): hep

Title: Hepatology (Baltimore, Md.)

Publisher: BlackWell Publishing Ltd (Oxford, UK )

ISSN (Print): 0270-9139

ISSN (Electronic): 1527-3350

Publication date (Print): December 2014

Publication date (Electronic): 29 October 2014

Volume: 60

Issue: 6

Pages: 1920-1928

Affiliations

[1 ]Division of Gastroenterology, University of California at San Diego La Jolla, CA

[2 ]NAFLD Translational Research Unit, Department of Medicine, University of California at San Diego La Jolla, CA

[3 ]Division of Epidemiology, Department of Family and Preventive Medicine, University of California at San Diego La Jolla, CA

[4 ]Departments of Mathematics, University of California at San Diego La Jolla, CA

[5 ]Pathology, University of California at San Diego La Jolla, CA

[6 ]Department of Pathology, Sharp Health System, San Diego, CA

[7 ]Department of Radiology, Mayo Clinic Rochester, MN

[8 ]Liver Imaging Group, Department of Radiology, University of California at San Diego La Jolla, CA

Author notes

Address reprint requests to: Rohit Loomba, M.D., M.H.Sc., Division of Gastroenterology and Epidemiology, University of California at San Diego, 9500 Gilman Drive, MC 0063, La Jolla, CA 92093. E-mail: roloomba@ 123456ucsd.edu ; fax: +1-858-534-3338 or Claude Sirlin, M.D., Liver Imaging Group, Department of Radiology, University of California at San Diego, 408 Dickinson Street, San Diego, CA 92103-8226. E-mail: csirlin@ 123456ucsd.edu ; Fax: +1-619-471-0503.

* These authors contributed equally to this work.

** Correction added after publication October 29, 2014: Author name Jonathan Booker was changed to Jonathan Hooker.

Additional Supporting Information may be found at onlinelibrary.wiley.com/doi/10.1002/hep.27362/suppinfo.

The study was conducted at the Clinical and Translational Research Institute, University of California at San Diego. R.L. is supported, in part, by the American Gastroenterological Association (AGA) Foundation (Sucampo) ASP Designated Research Award in Geriatric Gastroenterology and by a T. Franklin Williams Scholarship Award; funding provided by: Atlantic Philanthropies, Inc; the John A. Hartford Foundation, the Association of Specialty Professors, and the American Gastroenterological Association and grant K23-DK090303. Additional funding provided by R01DK088925 (principal investigator [PI]: C.S.) and National Institutes of Health grant EB001981 (PI: R.E.).

The study sponsor(s) had no role in the study design, collection, analysis, interpretation of the data, and/or drafting of the manuscript.

View this article online at wileyonlinelibrary.com.

Potential conflict of interest: Dr. Ehman owns stock in, holds intellectual property rights to, and received grants from Resoundant, Inc. Dr. Sirlin consults, advises, and is on the speakers’ bureau for Bayer. He received grants from GE Healthcare.

Article

DOI: 10.1002/hep.27362

PMC ID: 4245360

PubMed ID: 25103310

SO-VID: 1ce10574-515d-4ecd-bd08-80c59ad5631c

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This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Magnetic Resonance Elastography Predicts Advanced Fibrosis in Patients With Nonalcoholic Fatty Liver Disease: A Prospective Study

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Most cited references 27

Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis.

The natural history of nonalcoholic fatty liver disease: a population-based cohort study.

Magnetic resonance elastography of liver: technique, analysis, and clinical applications.

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