Advanced fibrosis in nonalcoholic fatty liver disease: noninvasive assessment with MR elastography.

PURPOSE To evaluate the diagnostic accuracy of magnetic resonance (MR) elastography as a method to help diagnose clinically substantial fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) and, by using MR elastography as a reference standard, to compare various laboratory marker panels in the identification of patients with NAFLD and advanced fibrosis. MATERIALS AND METHODS This retrospective study was institutional review board approved and HIPAA complaint. Informed consent was waived. This study was conducted in patients with NAFLD, who were identified by imaging characteristics consistent with steatosis in a prospective database that tracks all MR elastographic examinations. Six laboratory-based models of fibrosis were compared with MR elastographic results as well as fibrosis stage from liver biopsy results. The area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, positive predictive value, and negative predictive value of each data set were compared. RESULTS Among 325 patients with NAFLD with MR elastographic data, there were 142 patients who underwent liver biopsy within 1 year of MR elastography. When comparing MR elastography results with liver biopsy results, the best cutoff for advanced fibrosis (stage F3-F4, 46 [32.4%] of 142) was 4.15 kPa (AUROC = 0.954, sensitivity = 0.85, specificity = 0.929). This cutoff value identified 104 patients with advanced fibrosis (32.0% of 325 patients). The FIB-4 score (AUROC = 0.827) and NAFLD fibrosis score (AUROC = 0.821) had the best diagnostic accuracy for advanced fibrosis, with high negative predictive values (NAFLD fibrosis score = 0.90 and FIB-4 score = 0.899). CONCLUSION MR elastography is a useful diagnostic tool for detecting advanced fibrosis in NAFLD. Of the laboratory-based methods, the NAFLD fibrosis and FIB-4 scores can most reliably detect advanced fibrosis.

[1]  Julien Vergniol,et al.  Relative performances of FibroTest, Fibroscan, and biopsy for the assessment of the stage of liver fibrosis in patients with chronic hepatitis C: a step toward the truth in the absence of a gold standard. , 2012, Journal of hepatology.

[2]  Armando Manduca,et al.  Feasibility of in vivo MR elastographic splenic stiffness measurements in the assessment of portal hypertension. , 2009, AJR. American journal of roentgenology.

[3]  Sabrina Fox‐Bosetti,et al.  Test–retest repeatability of MR elastography for noninvasive liver fibrosis assessment in hepatitis C , 2011, Journal of magnetic resonance imaging : JMRI.

[4]  Scott B Reeder,et al.  Repeatability of magnetic resonance elastography for quantification of hepatic stiffness , 2010, Journal of magnetic resonance imaging : JMRI.

[5]  A. Pollett,et al.  Feasibility and diagnostic performance of the FibroScan XL probe for liver stiffness measurement in overweight and obese patients , 2012, Hepatology.

[6]  F. Brunello,et al.  Reliability of transient elastography for the detection of fibrosis in non-alcoholic fatty liver disease and chronic viral hepatitis. , 2011, Journal of hepatology.

[7]  Ewout W Steyerberg,et al.  Internal and external validation of predictive models: a simulation study of bias and precision in small samples. , 2003, Journal of clinical epidemiology.

[8]  E. Schiff,et al.  Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection , 2002, American Journal of Gastroenterology.

[9]  F. Carrat,et al.  How to measure the diagnostic accuracy of noninvasive liver fibrosis indices: the area under the ROC curve revisited. , 2008, Clinical chemistry.

[10]  J. Talwalkar,et al.  Noninvasive assessment of liver fibrosis , 2011, Hepatology.

[11]  B. Neuschwander‐Tetri,et al.  Development and validation of a simple NAFLD clinical scoring system for identifying patients without advanced disease , 2008, Gut.

[12]  M. Ziol,et al.  Novel controlled attenuation parameter for noninvasive assessment of steatosis using Fibroscan®: validation in chronic hepatitis C , 2012, Journal of viral hepatitis.

[13]  J. Habbema,et al.  Internal validation of predictive models: efficiency of some procedures for logistic regression analysis. , 2001, Journal of clinical epidemiology.

[14]  M. Charlton Nonalcoholic fatty liver disease: a review of current understanding and future impact. , 2004, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[15]  A. Feldstein,et al.  Diagnosis of Nonalcoholic Fatty Liver Disease: Invasive versus Noninvasive , 2008, Seminars in liver disease.

[16]  S. Sanderson,et al.  The natural history of nonalcoholic fatty liver disease: a population-based cohort study. , 2005, Gastroenterology.

[17]  J. Montaner,et al.  Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection , 2006, Hepatology.

[18]  Richard L Ehman,et al.  Cross‐validation of magnetic resonance elastography and ultrasound‐based transient elastography: A preliminary phantom study , 2009, Journal of magnetic resonance imaging : JMRI.

[19]  E. DeLong,et al.  Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. , 1988, Biometrics.

[20]  M. Colombo,et al.  Complications following percutaneous liver biopsy. A multicentre retrospective study on 68,276 biopsies. , 1986, Journal of hepatology.

[21]  Ralph Sinkus,et al.  Magnetic resonance elastography for the noninvasive staging of liver fibrosis. , 2008, Gastroenterology.

[22]  P. Giral,et al.  Sampling variability of liver biopsy in nonalcoholic fatty liver disease. , 2005, Gastroenterology.

[23]  Nancy A Obuchowski,et al.  Estimating and comparing diagnostic tests' accuracy when the gold standard is not binary. , 2005, Academic radiology.

[24]  D. Rockey,et al.  Noninvasive measures of liver fibrosis , 2006, Hepatology.

[25]  G. Casola,et al.  MR imaging of liver fibrosis: current state of the art. , 2009, Radiographics : a review publication of the Radiological Society of North America, Inc.

[26]  J. Kalbfleisch,et al.  A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C , 2003, Hepatology.

[27]  V. de Lédinghen,et al.  Standardization of ROC curve areas for diagnostic evaluation of liver fibrosis markers based on prevalences of fibrosis stages. , 2007, Clinical chemistry.

[28]  U. Motosugi,et al.  Cross‐validation of MR elastography and ultrasound transient elastography in liver stiffness measurement: discrepancy in the results of cirrhotic liver , 2012, Journal of magnetic resonance imaging : JMRI.

[29]  O. Cummings,et al.  Design and validation of a histological scoring system for nonalcoholic fatty liver disease , 2005, Hepatology.

[30]  V. de Lédinghen,et al.  Pitfalls of liver stiffness measurement: A 5‐year prospective study of 13,369 examinations , 2010, Hepatology.

[31]  A. Manduca,et al.  Magnetic resonance elastography by direct visualization of propagating acoustic strain waves. , 1995, Science.

[32]  Jonathan C. Cohen,et al.  Prevalence of hepatic steatosis in an urban population in the United States: Impact of ethnicity , 2004, Hepatology.

[33]  A. Manduca,et al.  Assessment of hepatic fibrosis with magnetic resonance elastography. , 2007, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[34]  I. Guha,et al.  Noninvasive markers of fibrosis in nonalcoholic fatty liver disease: Validating the European Liver Fibrosis Panel and exploring simple markers , 2007, Hepatology.

[35]  L. Ferrell,et al.  Correlation of paired liver biopsies in morbidly obese patients with suspected nonalcoholic fatty liver disease , 2006, Hepatology.

[36]  F. Pattou,et al.  Validation of noninvasive biomarkers (FibroTest, SteatoTest, and NashTest) for prediction of liver injury in patients with morbid obesity , 2011, European journal of gastroenterology & hepatology.

[37]  R. Ehman,et al.  Early detection of nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease by using MR elastography. , 2011, Radiology.

[38]  T. Therneau,et al.  The NAFLD fibrosis score: A noninvasive system that identifies liver fibrosis in patients with NAFLD , 2007, Hepatology.