Early detection of nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease by using MR elastography.

PURPOSE To investigate the diagnostic accuracy (area under the receiver operating characteristic curve [AUROC]) of magnetic resonance (MR) elastography for the early detection of nonalcoholic steatohepatitis (NASH) among patients with nonalcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS An institutional review board-approved and HIPAA-compliant retrospective study was conducted in 58 NAFLD patients. Informed consent was waived by the review board. Hepatic stiffness, relative fat fraction, inflammation grade, and fibrosis stage were assessed from MR elastography, in-phase and out-of-phase gradient-echo imaging, and liver biopsy histopathologic review, respectively. Pairwise t testing, receiver operating characteristic analysis, and partial correlation analysis were performed. RESULTS The mean hepatic stiffness for patients with simple steatosis (2.51 kPa) was less (P = .028) than that for patients with inflammation but no fibrosis (3.24 kPa). The mean hepatic stiffness for patients with inflammation but no fibrosis was less (P = .030) than that for patients with hepatic fibrosis (4.16 kPa). Liver stiffness had high accuracy (AUROC = 0.93) for discriminating patients with NASH from those with simple steatosis, with a sensitivity of 94% and a specificity 73% by using a threshold of 2.74 kPa. CONCLUSION In patients with NAFLD, hepatic stiffness measurements with MR elastography can help identify individuals with steatohepatitis, even before the onset of fibrosis; NAFLD patients with inflammation but no fibrosis have greater liver stiffness than those with simple steatosis and lower mean stiffness than those with fibrosis.

[1]  J. Ludwig,et al.  Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. , 1980, Mayo Clinic proceedings.

[2]  F. Schaffner,et al.  Nonalcoholic fatty liver disease. , 1986, Progress in liver diseases.

[3]  B J Ott,et al.  A 21-year experience with major hemorrhage after percutaneous liver biopsy. , 1990, Gastroenterology.

[4]  R. Hanson,et al.  The natural history of nonalcoholic steatohepatitis: A follow‐up study of forty‐two patients for up to 21 years , 1990, Hepatology.

[5]  I. Ranløv,et al.  Regression of liver steatosis following gastroplasty or gastric bypass for morbid obesity. , 1990, Digestion.

[6]  R. Buxton,et al.  Fatty infiltration of the liver: quantification with phase-contrast MR imaging at 1.5 T vs biopsy. , 1991, AJR. American journal of roentgenology.

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

[8]  H. Appelman,et al.  Regression of hepatic steatosis in morbidly obese persons after gastric bypass. , 1995, American journal of clinical pathology.

[9]  A. Scheen,et al.  Liver abnormalities in severely obese subjects: Effect of drastic weight loss after gastroplasty , 1998, International Journal of Obesity.

[10]  B. Neuschwander‐Tetri,et al.  Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions , 1999, American Journal of Gastroenterology.

[11]  J. F. Greenleaf,et al.  Magnetic resonance elastography: Non-invasive mapping of tissue elasticity , 2001, Medical Image Anal..

[12]  R. N. Macsween,et al.  Non-alcoholic steatohepatitis: a common cause of progressive chronic liver injury? , 2002, Journal of clinical pathology.

[13]  G. Leandro,et al.  Impact of liver biopsy size on histological evaluation of chronic viral hepatitis: the smaller the sample, the milder the disease. , 2003, Journal of hepatology.

[14]  P. Hayashi,et al.  The natural history of nonalcoholic fatty liver disease: a clinical histopathological study , 2003, American Journal of Gastroenterology.

[15]  S. Thung,et al.  Effects of surgical treatment of the metabolic syndrome on liver fibrosis and cirrhosis. , 2004, Surgery.

[16]  J. Dixon,et al.  Nonalcoholic fatty liver disease: Improvement in liver histological analysis with weight loss , 2004, Hepatology.

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

[18]  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.

[19]  J. Kench,et al.  Improved prediction of fibrosis in chronic hepatitis C using measures of insulin resistance in a probability index , 2004, Hepatology.

[20]  Wilson Fong Handbook of MRI Pulse Sequences , 2005 .

[21]  J. Hoofnagle,et al.  A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis , 2004, Hepatology.

[22]  E. Fassio,et al.  Natural history of nonalcoholic steathepatitis: A longitudinal study of repeat liver biopsies , 2004, Hepatology.

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

[24]  R. Wells The role of matrix stiffness in hepatic stellate cell activation and liver fibrosis. , 2005, Journal of clinical gastroenterology.

[25]  T. Magnuson,et al.  Roux-en-Y gastric bypass improves liver histology in patients with non-alcoholic fatty liver disease. , 2005, Obesity research.

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

[27]  H. Hussain,et al.  Hepatic fat fraction: MR imaging for quantitative measurement and display--early experience. , 2005, Radiology.

[28]  A. Krasinskas,et al.  Surgically-Induced Weight Loss Significantly Improves Nonalcoholic Fatty Liver Disease and the Metabolic Syndrome , 2005, Annals of surgery.

[29]  F. Kinjo,et al.  Clinical usefulness of biochemical markers of liver fibrosis in patients with nonalcoholic fatty liver disease. , 2005, World journal of gastroenterology.

[30]  Christos Christidis,et al.  Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C , 2005, Hepatology.

[31]  G. Marchesini,et al.  A Randomized Controlled Trial of Metformin versus Vitamin E or Prescriptive Diet in Nonalcoholic Fatty Liver Disease , 2005, The American Journal of Gastroenterology.

[32]  H. Conjeevaram,et al.  One-Year Intense Nutritional Counseling Results in Histological Improvement in Patients with Nonalcoholic Steatohepatitis: A Pilot Study , 2005, The American Journal of Gastroenterology.

[33]  R. Standish,et al.  An appraisal of the histopathological assessment of liver fibrosis , 2006, Gut.

[34]  X. Forns,et al.  Transient elastography for diagnosis of advanced fibrosis and portal hypertension in patients with hepatitis C recurrence after liver transplantation , 2006, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[35]  R. Malekzadeh,et al.  Noninvasive Markers of Liver Fibrosis and Inflammation in Chronic Hepatitis B-Virus Related Liver Disease , 2006, The American Journal of Gastroenterology.

[36]  Giacomo Belli,et al.  Liver stiffness measurement predicts severe portal hypertension in patients with HCV‐related cirrhosis , 2007, Hepatology.

[37]  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.

[38]  P. Janmey,et al.  Increased stiffness of the rat liver precedes matrix deposition: implications for fibrosis. , 2007, American journal of physiology. Gastrointestinal and liver physiology.

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

[40]  J. Dranoff,et al.  Transforming growth factor‐β and substrate stiffness regulate portal fibroblast activation in culture , 2007, Hepatology.

[41]  H. Aburatani,et al.  Plasma Pentraxin3 is a Novel Marker for Nonalcoholic Steatohepatitis (NASH) , 2008, BMC gastroenterology.

[42]  B. Hillner,et al.  A decision analysis study of the value of a liver biopsy in nonalcoholic steatohepatitis , 2008, Liver international : official journal of the International Association for the Study of the Liver.

[43]  I. Sporea,et al.  Why, who and how should perform liver biopsy in chronic liver diseases. , 2008, World journal of gastroenterology.

[44]  Dieter Klatt,et al.  Assessment of liver viscoelasticity using multifrequency MR elastography , 2008, Magnetic resonance in medicine.

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

[46]  Azmat Ali,et al.  Magnetic resonance imaging and spectroscopy for monitoring liver steatosis , 2008, Journal of magnetic resonance imaging : JMRI.

[47]  J M Peron,et al.  Transient elastography accurately predicts presence of significant portal hypertension in patients with chronic liver disease , 2008, Alimentary pharmacology & therapeutics.

[48]  R. Wells The role of matrix stiffness in regulating cell behavior , 2008, Hepatology.

[49]  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.

[50]  J. Talwalkar Elastography for detecting hepatic fibrosis: options and considerations. , 2008, Gastroenterology.

[51]  Richard L Ehman,et al.  Magnetic resonance imaging of hepatic fibrosis: Emerging clinical applications , 2007, Hepatology.

[52]  D. Schuppan,et al.  The clinical utility of biomarkers and the nonalcoholic steatohepatitis CRN liver biopsy scoring system in patients with nonalcoholic fatty liver disease , 2009, Journal of gastroenterology and hepatology.

[53]  A. Feldstein,et al.  Cytokeratin‐18 fragment levels as noninvasive biomarkers for nonalcoholic steatohepatitis: A multicenter validation study , 2009, Hepatology.

[54]  H. Saitsu,et al.  Validity of FibroScan values for predicting hepatic fibrosis stage in patients with chronic HCV infection , 2009, Journal of digestive diseases.

[55]  Lungen Lu,et al.  Assessment of fibrosis in chronic liver diseases , 2009, Journal of digestive diseases.

[56]  J. Talwalkar One step at a time: Identification and validation of biomarkers for nonalcoholic steatohepatitis , 2009, Hepatology.

[57]  Mathias Fink,et al.  Early detection of steatohepatitis in fatty rat liver by using MR elastography. , 2009, Radiology.

[58]  R. Ehman,et al.  Science to practice: can MR elastography be used to detect early steatohepatitis in fatty liver disease? , 2009, Radiology.

[59]  Z. Sparchez,et al.  Performance of unidimensional transient elastography in staging non-alcoholic steatohepatitis. , 2010, Journal of gastrointestinal and liver diseases : JGLD.

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