Establishment of a general NAFLD scoring system for rodent models and comparison to human liver pathology.
Establishment of a general NAFLD scoring system for rodent models and comparison to human liver pathology.
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DOI：
10.1371/journal.pone.0115922
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
van den Hoek AM
中科院分区：
文献类型：
--
作者：
Liang W;Menke AL;Driessen A;Koek GH;Lindeman JH;Stoop R;Havekes LM;Kleemann R;van den Hoek AM
NASH临床研究网络（NASH- crn）最近开发的非酒精性脂肪性肝病（NAFLD）的组织学评分系统已广泛应用于临床环境，但也越来越多地用于临床前研究。然而，人类评分系统是否可以直接转化为临床前啮齿动物模型，目前还没有系统的分析。为了分析这一点，我们系统地比较了人类NAFLD的肝脏病理，使用人类肝脏活检，与几种NAFLD小鼠模型的肝脏病理。基于小鼠NAFLD的特征，我们的目标是建立一个改良的通用评分系统，适用于广泛的啮齿动物模型。在几种不同的NAFLD小鼠模型中分析NAFLD的组织病理学，以确定组织评估的通用标准（临床前评分系统）。为了验证该评分系统，由10名观察员对36张覆盖NAFLD全谱的小鼠肝脏切片进行盲法分析。此外，在间隔超过3个月的两次单独评估中，由一名观察员对肝脏进行盲目评分。大泡性脂肪变性、微泡性脂肪变性、肝细胞肥大、炎症和纤维化标准普遍适用于啮齿动物NAFLD。在分析大泡性脂肪变性和微泡性脂肪变性时，10个观察者之间的观察者间可重复性（使用类内相关系数进行评估）为高（ICC = 0.784和0.776，均p<0.001，分别），而在分析肥厚和炎症时，可重复性为中等（ICC = 0.685和0.650，均p<0.001）。对于大泡性脂肪变性、微泡性脂肪变性和肥厚的分析，同一观察者不同观察结果之间的观察者内重现性很高（ICC = 0.871、0.871和0.896，p均<0.001），对于炎症的分析，其观察者内重现性非常高（ICC = 0.931, p<0.001）。我们建立了一个简单的NAFLD评分系统，具有高重复性，适用于不同的啮齿动物模型和NAFLD病因的所有阶段。
The recently developed histological scoring system for non-alcoholic fatty liver disease (NAFLD) by the NASH Clinical Research Network (NASH-CRN) has been widely used in clinical settings, but is increasingly employed in preclinical research as well. However, it has not been systematically analyzed whether the human scoring system can directly be converted to preclinical rodent models. To analyze this, we systematically compared human NAFLD liver pathology, using human liver biopsies, with liver pathology of several NAFLD mouse models. Based upon the features pertaining to mouse NAFLD, we aimed at establishing a modified generic scoring system that is applicable to broad spectrum of rodent models. The histopathology of NAFLD was analyzed in several different mouse models of NAFLD to define generic criteria for histological assessment (preclinical scoring system). For validation of this scoring system, 36 slides of mouse livers, covering the whole spectrum of NAFLD, were blindly analyzed by ten observers. Additionally, the livers were blindly scored by one observer during two separate assessments longer than 3 months apart. The criteria macrovesicular steatosis, microvesicular steatosis, hepatocellular hypertrophy, inflammation and fibrosis were generally applicable to rodent NAFLD. The inter-observer reproducibility (evaluated using the Intraclass Correlation Coefficient) between the ten observers was high for the analysis of macrovesicular steatosis and microvesicular steatosis (ICC = 0.784 and 0.776, all p<0.001, respectively) and moderate for the analysis of hypertrophy and inflammation (ICC = 0.685 and 0.650, all p<0.001, respectively). The intra-observer reproducibility between the different observations of one observer was high for the analysis of macrovesicular steatosis, microvesicular steatosis and hypertrophy (ICC = 0.871, 0.871 and 0.896, all p<0.001, respectively) and very high for the analysis of inflammation (ICC = 0.931, p<0.001). We established a simple NAFLD scoring system with high reproducibility that is applicable for different rodent models and for all stages of NAFLD etiology.
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影响因子：
5
作者：
Liang, Wen;Lindeman, Jan H.;Kleemann, Robert
通讯作者：
Kleemann, Robert
影响因子：
4.2
作者：
Fukusato, T;Fukushima, J;Yoshimura, K
通讯作者：
Yoshimura, K
影响因子：
15.9
作者：
JIANG, XC;AGELLON, LB;TALL, A
通讯作者：
TALL, A
影响因子：
20.1
作者：
Verschuren L;Kooistra T;Bernhagen J;Voshol PJ;Ouwens DM;van Erk M;de Vries-van der Weij J;Leng L;van Bockel JH;van Dijk KW;Fingerle-Rowson G;Bucala R;Kleemann R
通讯作者：
Kleemann R
影响因子：
13.5
作者：
Kleiner, DE;Brunt, EM;Sanyal, AJ
通讯作者：
Sanyal, AJ