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Stratifying Non-alcoholic Steatohepatitis With the Non-invasive Ultrasound Markers Shear Wave Dispersion Slope and Shear Wave Velocity: An Animal Study

      Abstract

      We evaluated the significance of the ultrasound (US) markers shear wave dispersion slope (SWDS) and shear wave velocity (SWV) for identification of non-alcoholic steatohepatitis (NASH) and high-risk NASH; the latter was defined as the presence of steatohepatitis, a non-alcoholic fatty liver disease activity score (NAS) ≥4 or a fibrosis stage ≥2. Thirty-six male Sprague-Dawley (SD) rats were assigned to two groups: the study (n = 30) and control (n = 6) groups. To initiate non-alcoholic steatohepatitis, study group rats were fed a diet deficient in methionine and choline. All rats were examined using ultrasonography to obtain the SWDS and SWV parameters of the liver at the same time points. Fatty liver pathological grades were determined after euthanasia; the livers were categorized in the normal (n = 6), NAFL (non-alcoholic fatty liver) (n = 10) and NASH (n = 20) subgroups based on the NAS scoring system. They were also categorized into subgroups F0 (n = 22), F1 (n = 3), F2 (n = 7) and F3 (n = 4) on the basis of the METAVIR (Meta-analysis of Histological Data in Viral Hepatitis) scoring system. Measurement differences between various grades were evaluated by analysis of variance (ANOVA) or the Mann–Whitney U-test. We used logistic regression to calculate a combination of the two parameters for combined assessment of parameters. The diagnostic value of SWDS, SWV and the two-variable model was determined by receiver operating characteristic (ROC) curve analysis. This analysis revealed stepwise increases in SWDS and SWV with increasing NAFLD severity. The accuracy of SWDS in diagnosing NASH was good (area under the ROC curve [AUC]: 0.88) and was superior to that of SWV (AUC: 0.76). The combination of SWV and SWDS exhibited higher performance (AUC: 0.90). SWV was higher than SWDS in participants with a fibrosis grade ≥2 (high-risk NASH). For identification of high-risk NASH, SWV exhibited the best diagnostic performance (AUC: 0.89), which was equivalent to that of the two-variable model (AUC: 0.88) and slightly higher than that of SWDS (AUC: 0.85). This study indicates that of the US-based markers, SWDS outperforms SWV in identifying NASH in rats and that combining the two markers may increase their clinical utility in guiding NAFLD and NASH treatment.

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