非酒精性脂肪性肝病诊断——病理的重要性

田爱平; 杨永峰

doi:10.3969/j.issn.1001-5256.2023.03.002

非酒精性脂肪性肝病诊断——病理的重要性

DOI: 10.3969/j.issn.1001-5256.2023.03.002

田爱平¹,
杨永峰^2, , ,

1.
兰州大学第一医院感染科，兰州 730000
2.
南京中医药大学附属南京医院(南京市第二医院) 肝病科，南京 210003

基金项目:

甘肃省高等学校创新能力提升项目 (2020B-016);

兰州大学第一医院院内基金 (ldyyyn2018-62)

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：田爱平负责撰写文章；杨永峰负责修改和审核文章。

详细信息

通信作者:
杨永峰，yyf1997@163.com (ORCID: 0000-0002-3214-0038)

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出版历程
- 收稿日期: 2022-01-15
- 录用日期: 2022-02-20
- 出版日期: 2023-03-20

Diagnosis of nonalcoholic fatty liver disease: The importance of pathology

Aiping TIAN¹,
Yongfeng YANG^{2
, ,
,}

1.
Department of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou 730000, China
2.
Department of Hepatology, Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine & Nanjing Second Hospital, Nanjing 210003, China

Research funding:

Gansu Province Academic Innovative Promotion (2020B-016);

The Inner Project of the 1st hospital of Lanzhou University (ldyyyn2018-62)

More Information

Corresponding author: YANG Yongfeng, yyf1997@163.com (ORCID: 0000-0002-3214-0038)

摘要

摘要: 对于非酒精性脂肪性肝病的明确诊断、单纯性脂肪肝(NAFL)及非酒精性脂肪性肝炎(NASH)区分及疾病严重程度的分级评分，均需依靠肝穿刺活检组织病理学评估完成，而临床上仍多依赖于血液学及影像学检测手段。尽管目前已有大量相关研究针对非酒精性脂肪性肝病的无创纤维化评估、疾病诊断模型出现，其敏感性及特异性仍有待提高。本文拟分别从NAFL及NASH的主要病理学特征、纤维化及分级分期评分方法，NASH肝硬化的病理学诊断等方面进行论述，以期提高临床医师对于该疾病组织学诊断的重视。
- 非酒精性脂肪性肝病 /
- 病理学 /
- 诊断, 鉴别
Abstract: Histopathological evaluation based on liver biopsy is required to make a confirmed diagnosis of nonalcoholic fatty liver disease, differentiate nonalcoholic fatty liver (NAFL) from nonalcoholic steatohepatitis (NASH), and perform the grading and scoring of disease severity, while hematological and radiological examinations are often used in clinical practice. Although there have been a large number of studies on noninvasive models for fibrosis assessment and disease diagnosis in nonalcoholic fatty liver disease, the sensitivity and specificity of such models need to be further improved. This article reviews the main pathological features of NAFL and NASH, fibrosis and grading/staging/scoring systems, and the pathological diagnosis of NASH liver cirrhosis, in order to improve the awareness of the histological diagnosis of such disease among clinicians
- Non-alcoholic Fatty Liver Disease /
- Pathology /
- Diagnosis, Differential

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图 1 NAFLD/NASH主要病理特征(HE染色，×200)^[2]

注: a, 肝细胞大泡脂肪变性；b, 肝细胞中泡脂肪变性；c, 肝细胞微泡脂肪变性；d, 肝细胞气球样变性；e, 肝细胞炎症坏死；f, 卫星现象。

Figure 1. Major patholothy injury characteristic of NAFLD/NASH(HE staining, ×200)^[2]

下载: 全尺寸图片幻灯片

图 2 NAFLD不同程度纤维化(Masson染色，×100)^[2]

注：a，窦周纤维化；b，汇管区和小叶均出现纤维化；c，桥接纤维华形成；d，NASH肝硬化。

Figure 2. Different stage of NAFLD fibrosis (Masson staining, ×100)^[2]

下载: 全尺寸图片幻灯片

表 1 CRN提出的NAFLD/NASH病理诊断分级NAS评分法

Table 1. NAS scoring of NAFLD/NASH

组织学特征	评分	诊断标准
脂肪变性(低倍镜)	0	＜5%
	1	5%~33%
	2	34%~66%
	3	＞66%
肝细胞气球样变性	0	无
	1	少量
	2	数量较多，同时形态较为明显
小叶炎症(所有炎症病灶)	0	无
	1	＜2点灶坏死/20倍镜视野
	2	2~4点灶坏死/20倍镜视野
	3	＞4点灶坏死/20倍镜视野
NAS总分	0~8

下载: 导出CSV

表 2 NASH CRN修改的Brunt分期系统

Table 2. Brunt scoring system after CRN modified

分期	诊断标准
0	无
1
1a	轻度，腺泡3区窦周纤维化，需Masson染色辨认
1b	中度，腺泡3区-窦周纤维化，HE染色即可辨认
1c	仅汇管区/汇管区周围纤维化
2	1期+汇管区/汇管区周围纤维化，局灶或广泛
3	桥接纤维化，局灶或广泛
4	肝硬化(+/-残余窦周纤维化)

下载: 导出CSV

表 3 NAFLD/NASH SAF评分

Table 3. SAF scoring system of NAFLD/NASH

病理学特征	评分	诊断标准
脂肪变性(S)	0~3
	0	＜5%
	1	5%~33%
	2	34%~66%
	3	＞66%
炎症评分(A)	0~4
包括肝细胞气球样变性+小叶炎症
肝细胞气球样变性	0	无
	1	圆形的胞质疏松淡染的肝细胞成簇
	2	圆形的胞质疏松淡染的肝细胞成簇并大于两倍正常肝细胞体积
小叶炎症(所有炎症病灶)	0	无
	1	＜2个点灶/20倍视野
	2	＞2个点灶/20倍视野
纤维化评分(F)	0~4
纤维化程度	0	无
	1a	轻度，腺泡3区/窦周纤维化仅胶原染色可见
	1b	中度，腺泡3区/窦周纤维化
	1c	仅汇管区/汇管区周边纤维化
	2	腺泡3区/窦周纤维化+汇管区纤维化
	3	桥接纤维化
	4	肝硬化

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表 4 NASH肝硬化诊断相关定义：肝病论坛共识

Table 4. NASH cirrhosis definition: Liver forum consensus

确定	很可能	可能
a.病理表现同时具备NASH和肝硬化	a.既往病理诊断NAFL，现发展为肝硬化有或曾有2项以上代谢综合征(包括肥胖和/或T2DM)	a.隐源性肝硬化，无脂肪肝证据有或曾有1项以上代谢综合征(包括肥胖和/或T2DM)
b.既往病理诊断NASH，现发展为肝硬化有或曾有1项以上代谢综合征	b.肝硬化，目前或既往影像提示脂肪肝，无组织学证据有或曾有2项以上代谢综合征(包括肥胖和/或T2DM)	b.既往HCV清除，或既往曾有酗酒史，现有肝硬化+NASH组织学证据
c.现病理NAFL+肝硬化，并排除其他病因有或曾有2项以上代谢综合征(包括肥胖和/或T2DM)	c.隐源性肝硬化，无脂肪肝证据有或曾有2项以上代谢综合征(包括肥胖和/或T2DM)

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