The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
Alcohol Clin Exp Res. 2021 Oct;45(10):2103-2117. doi: 10.1111/acer.14699. Epub 2021 Sep 5.
Magnetic resonance imaging (MRI) and MRI-based elastography (MRE) are the most promising noninvasive techniques in assessing liver diseases. The purpose of this study was to evaluate an advanced multiparametric imaging method for staging disease and assessing treatment response in realistic preclinical alcohol-associated liver disease (ALD).
We utilized four different preclinical mouse models in our study: Model 1-mice were fed a fast-food diet and fructose water for 48 weeks to induce nonalcoholic fatty liver disease; Model 2-mice were fed chronic-binge ethanol (EtOH) for 10 days or 8 weeks to induce liver steatosis/inflammation. Two groups of mice were treated with interleukin-22 at different time points to induce disease regression; Model 3-mice were administered CCl for 2 to 4 weeks to establish liver fibrosis followed by 2 or 4 weeks of recovery; and Model 4-mice were administered EtOH plus CCl for 12 weeks. Mouse liver imaging biomarkers including proton density fat fraction (PDFF), liver stiffness (LS), loss modulus (LM), and damping ratio (DR) were assessed. Liver and serum samples were obtained for histologic and biochemical analyses. Ordinal logistic regression and generalized linear regression analyses were used to model the severity of steatosis, inflammation, and fibrosis, and to assess the regression of these conditions.
Multiparametric models with combinations of biomarkers (LS, LM, DR, and PDFF) used noninvasively to predict the histologic severity and regression of steatosis, inflammation, and fibrosis were highly accurate (area under the curve > 0.84 for all). A three-parameter model that incorporates LS, DR, and ALT predicted histologic fibrosis progression (r = 0.84, p < 0.0001) and regression (r = 0.79, p < 0.0001) as measured by collagen content in livers.
This preclinical study provides evidence that multiparametric MRI/MRE can be used noninvasively to assess disease severity and monitor treatment response in ALD.
磁共振成像（MRI）和基于 MRI 的弹性成像（MRE）是评估肝脏疾病最有前途的非侵入性技术。本研究的目的是评估一种先进的多参数成像方法，用于分期疾病并评估现实临床前酒精性肝病（ALD）的治疗反应。
我们在研究中利用了四种不同的临床前小鼠模型：模型 1-小鼠喂食快餐饮食和果糖水 48 周以诱导非酒精性脂肪肝；模型 2-小鼠喂食慢性 binge 乙醇（EtOH）10 天或 8 周以诱导肝脂肪变性/炎症。两组小鼠在不同时间点用白细胞介素-22 治疗以诱导疾病消退；模型 3-小鼠接受 CCl 治疗 2 至 4 周以建立肝纤维化，然后恢复 2 或 4 周；模型 4-小鼠给予 EtOH 和 CCl 治疗 12 周。评估了包括质子密度脂肪分数（PDFF）、肝硬度（LS）、损耗模量（LM）和阻尼比（DR）在内的小鼠肝脏成像生物标志物。获取肝和血清样本进行组织学和生化分析。使用有序逻辑回归和广义线性回归分析对脂肪变性、炎症和纤维化的严重程度进行建模，并评估这些情况的消退。
使用结合了生物标志物（LS、LM、DR 和 PDFF）的多参数模型，非侵入性地预测了脂肪变性、炎症和纤维化的组织学严重程度和消退，具有很高的准确性（所有的曲线下面积>0.84）。一个包含 LS、DR 和 ALT 的三参数模型预测了肝脏胶原含量测量的组织纤维化进展（r=0.84，p<0.0001）和消退（r=0.79，p<0.0001）。
这项临床前研究提供了证据，表明多参数 MRI/MRE 可用于非侵入性地评估 ALD 中的疾病严重程度并监测治疗反应。
