Shear Wave Elastography for Assessment of Steatohepatitis and Hepatic Fibrosis in Rat Models of Non-Alcoholic Fatty Liver Disease.

The purpose of this study was to evaluate shear wave elastography (SWE) as a method for determining the severity of non-alcoholic fatty liver disease (NAFLD) and the stage of hepatic fibrosis, as well as the major determinants of liver elasticity among the various histologic and biomolecular changes associated with NAFLD. Rat NAFLD models with various degrees of NAFLD severity were created and imaged using SWE. The explanted livers were subjected to histopathologic evaluation and RNA expression analysis. Among the histologic and biomolecular findings, the fibrosis stage and the collagen RNA level were significant independent factors associated with liver elasticity (p < 0.001). Liver elasticity was effective in detecting non-alcoholic steatohepatitis (NASH) and in determining fibrosis stage, and the corresponding areas under the receiver operating characteristic curves were 0.963 and 0.927-0.997, respectively. In conclusion, SWE is a potential non-invasive method for the detection of NASH and staging of hepatic fibrosis in patients with NAFLD.

[1]  Virginia Nguyen,et al.  Kuppfer Cells Trigger Nonalcoholic Steatohepatitis Development in Diet-induced Mouse Model through Tumor Necrosis Factor-α Production* , 2012, The Journal of Biological Chemistry.

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

[3]  Simona Bota,et al.  The role of ultrasound elastographic techniques in chronic liver disease: current status and future perspectives. , 2014, European journal of radiology.

[4]  A. Feldstein,et al.  Noninvasive diagnosis and monitoring of nonalcoholic steatohepatitis: Present and future , 2007, Hepatology.

[5]  B. Neuschwander‐Tetri,et al.  Nonalcoholic steatohepatitis: Summary of an AASLD Single Topic Conference , 2003, Hepatology.

[6]  Anil T Ahuja,et al.  Quantitative elastography of liver fibrosis and spleen stiffness in chronic hepatitis B carriers: comparison of shear-wave elastography and transient elastography with liver biopsy correlation. , 2013, Radiology.

[7]  Ioan Sporea,et al.  Value of acoustic radiation force impulse imaging elastography for non-invasive evaluation of patients with nonalcoholic fatty liver disease. , 2013, Ultrasound in medicine & biology.

[8]  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.

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

[10]  Huiman X Barnhart,et al.  Applications of the repeatability of quantitative imaging biomarkers: a review of statistical analysis of repeat data sets. , 2009, Translational oncology.

[11]  Yongping Lu,et al.  Evaluation of fatty liver fibrosis in rabbits using real-time shear wave elastography , 2014, Experimental and therapeutic medicine.

[12]  M. Tanter,et al.  Investigating liver stiffness and viscosity for fibrosis, steatosis and activity staging using shear wave elastography. , 2015, Journal of hepatology.

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

[14]  Viv Bewick,et al.  Statistics review 13: Receiver operating characteristic curves , 2004, Critical care.

[15]  G. Ferraioli,et al.  Accuracy of real‐time shear wave elastography for assessing liver fibrosis in chronic hepatitis C: A pilot study , 2012, Hepatology.

[16]  Eva Herrmann,et al.  Liver fibrosis in viral hepatitis: noninvasive assessment with acoustic radiation force impulse imaging versus transient elastography. , 2009, Radiology.

[17]  H. Tilg,et al.  Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis , 2010, Hepatology.

[18]  P. Angulo.  GI Epidemiology: nonalcoholic fatty liver disease , 2007, Alimentary pharmacology & therapeutics.

[19]  Gabriela Marinoschi,et al.  Acoustic radiation force imaging sonoelastography for noninvasive staging of liver fibrosis. , 2009, World journal of gastroenterology.

[20]  P. Cheah,et al.  Performance of transient elastography (TE) and factors associated with discordance in non‐alcoholic fatty liver disease , 2013, Journal of digestive diseases.

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

[22]  K. Nightingale,et al.  Derivation and analysis of viscoelastic properties in human liver: impact of frequency on fibrosis and steatosis staging , 2015, IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control.

[23]  Hyoung-Ki Lee,et al.  Principles and clinical application of ultrasound elastography for diffuse liver disease , 2014, Ultrasonography.

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

[25]  Julien Vergniol,et al.  Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease , 2010, Hepatology.

[26]  Ned C. Rouze,et al.  Noninvasive evaluation of hepatic fibrosis using acoustic radiation force-based shear stiffness in patients with nonalcoholic fatty liver disease. , 2011, Journal of hepatology.

[27]  Kunihiro Hosono,et al.  Nonalcoholic fatty liver disease: US-based acoustic radiation force impulse elastography. , 2010, Radiology.

[28]  P. Angulo,et al.  Nonalcoholic fatty liver disease. , 2002, Revista de gastroenterologia de Mexico.

[29]  M. Fink,et al.  Supersonic shear imaging: a new technique for soft tissue elasticity mapping , 2004, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[30]  H. Kirikoshi,et al.  Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with nonalcoholic fatty liver disease (NAFLD). , 2008, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[31]  T. Luedde,et al.  Pharmacological inhibition of the chemokine CCL2 (MCP-1) diminishes liver macrophage infiltration and steatohepatitis in chronic hepatic injury , 2011, Gut.

[32]  Anthony Gamst,et al.  Magnetic Resonance Elastography Predicts Advanced Fibrosis in Patients With Nonalcoholic Fatty Liver Disease: A Prospective Study , 2014, Hepatology.

[33]  Jian-Gao Fan,et al.  Commonly used animal models of non-alcoholic steatohepatitis. , 2009, Hepatobiliary & pancreatic diseases international : HBPD INT.

[34]  Peter Neuhaus,et al.  Surgical anatomy of the liver, hepatic vasculature and bile ducts in the rat , 2007, Liver international : official journal of the International Association for the Study of the Liver.

[35]  W. An,et al.  Roles of liver innate immune cells in nonalcoholic fatty liver disease. , 2010, World journal of gastroenterology.

[36]  F. Piscaglia,et al.  Expression of reelin in hepatic stellate cells and during hepatic tissue repair: a novel marker for the differentiation of HSC from other liver myofibroblasts. , 2002, Journal of hepatology.