title: Hepatic Alanine Differentiates Nonalcoholic Steatohepatitis From Simple Steatosis in Humans and Mice: A Proton MR Spectroscopy Study With Long Echo Time.
abstract: To evaluate the hepatic metabolic alterations in nonalcoholic fatty liver disease (NAFLD) by using1H-MRS (proton magnetic resonance spectroscopy) with long echo time and to test the reproducibility of human study in an animal model. Liver biopsy is the gold standard for diagnosing NAFLD but with practical constraints.1H-MRS allows in vivo assessment of hepatocellular metabolism and has shown potential for biochemical differentiation in diffuse liver disease.
  
  
  
  In all, 32 subjects (11 patients with nonalcoholic steatohepatitis [NASH], 15 with simple steatosis [SS], and six healthy controls) were studied. For test reproducibility, 36 C57BL/6 mice, including 10 mice with streptozotocin-induced NASH, 15 with SS, and 11 high-fat diet controls, were studied.1H-MRS measurements at 3T and 4.7T MRI were performed on a localized voxel of the liver using PRESS sequence. Hepatic alanine (Ala), lactate+triglyceride (Lac+TG), and TG levels were compared between NASH, SS, and control groups using analysis of variance (ANOVA) tests. Diagnostic accuracy was determined by calculating the area under the receiver operating characteristics (ROC) curve. The associations between metabolite levels and pathologic grades or NAFLD activity scores (NAS) were assessed using Pearson's correlation.
  
  
  
  NASH patients had higher levels of Ala (P < 0.001), Lac+TG (P < 0.001), and TG (P < 0.05) than SS patients or controls. The AUROC curve to distinguish NASH from SS was 1.00 (95% confidence interval [CI] 1.00-1.00) for Ala and 0.782 (95% CI 0.61-0.96) for Lac+TG. Ala and Lac+TG concentrations were positively correlated with steatosis grade (Ala Pearson's r = 0.723; Lac+TG r = 0.446), lobular inflammation (Ala r = 0.513), and NAS (Ala r = 0.743; Lac+TG r = 0.474).
  
  
  
  1H-MRS is potentially useful for noninvasive diagnosis of NASH and simple steatosis by hepatic metabolite quantification.
  
  
  
  2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1298-1310.
authors.affiliation: Imaging Science Research Center, Wonkwang University, Iksan, Republic of Korea.
authors.forename: Tae-Hoon
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Imaging Science Research Center, Wonkwang University, Iksan, Republic of Korea.
authors.forename: Hong Young
authors.initials: HY
authors.lastname: Jun
authors.affiliation: Department of Radiology, Wonkwang University School of Medicine, Iksan, Republic of Korea.
authors.forename: Ki-Jong
authors.initials: KJ
authors.lastname: Kim
authors.affiliation: Imaging Science Research Center, Wonkwang University, Iksan, Republic of Korea.|Department of Radiology, Wonkwang University School of Medicine, Iksan, Republic of Korea.
authors.forename: Young Hwan
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Imaging Science Research Center, Wonkwang University, Iksan, Republic of Korea.|Department of Internal Medicine, Wonkwang University School of Medicine, Iksan, Republic of Korea.
authors.forename: Myeung Su
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Department of Pathology, Wonkwang University School of Medicine, Iksan, Republic of Korea.
authors.forename: Keum Ha
authors.initials: KH
authors.lastname: Choi
authors.affiliation: Department of Pathology, Wonkwang University School of Medicine, Iksan, Republic of Korea.
authors.forename: Ki Jung
authors.initials: KJ
authors.lastname: Yun
authors.affiliation: Department of Radiology, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Yong Yeon
authors.initials: YY
authors.lastname: Jeong
authors.affiliation: Department of Internal Medicine, Chonnam National University Hospital, Gwangju, Republic of Korea.
authors.forename: Chung Hwan
authors.initials: CH
authors.lastname: Jun
authors.affiliation: Department of Internal Medicine, Wonkwang University School of Medicine, Iksan, Republic of Korea.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Cho
authors.affiliation: Imaging Science Research Center, Wonkwang University, Iksan, Republic of Korea.|Department of Radiology, Wonkwang University School of Medicine, Iksan, Republic of Korea.
authors.forename: Kwon-Ha
authors.identifier: 0000-0002-2634-8510
authors.initials: KH
authors.lastname: Yoon
mesh_terms: D000328:Adult; D000409:Alanine / Q000378:metabolism*; D000818:Animals; D019540:Area Under Curve; D001706:Biopsy; D016022:Case-Control Studies; D005234:Fatty Liver / Q000000981:diagnostic imaging* / Q000378:metabolism; D005260:Female; D022781:Hepatocytes / Q000166:cytology; D006801:Humans; D008099:Liver / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D011446:Prospective Studies; D011522:Protons; D012372:ROC Curve; D015203:Reproducibility of Results
chemical_list: D011522:Protons; D000409:Alanine
keywords: hepatic metabolites; nonalcoholic fatty liver disease (NAFLD); nonalcoholic steatohepatitis (NASH); proton magnetic resonance spectroscopy (1H MRS)