Hepatic Alanine Differentiates Nonalcoholic Steatohepatitis From Simple Steatosis in Humans and Mice: A Proton MR Spectroscopy Study With Long Echo Time

5 years ago

Hepatic Alanine Differentiates Nonalcoholic Steatohepatitis From Simple Steatosis in Humans and Mice: A Proton MR Spectroscopy Study With Long Echo Time

Ki Jung Yun, Hong Young Jun, Myeung Su Lee, Young Hwan Lee, Tae-Hoon Kim, Keum Ha Choi, Yong Yeon Jeong, Ki-Jong Kim, Kwon-Ha Yoon, Eun Young Cho, Chung Hwan Jun

Purpose To evaluate the hepatic metabolic alterations in nonalcoholic fatty liver disease (NAFLD) by using 1H-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. Materials and Methods 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. Results 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). Conclusion 1H-MRS is potentially useful for noninvasive diagnosis of NASH and simple steatosis by hepatic metabolite quantification. Level of Evidence: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1298–1310.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/jmri.25673