肝纤维化非创伤性实验诊断专家共识

doi:10.3969/j.issn.1673-8640.2025.07.001

摘要/Abstract

摘要：

肝纤维化是肝脏对各种慢性损伤的病理性修复反应。早期诊断和干预能够延缓甚至逆转肝纤维化。目前，临床上仍缺乏特异性的肝纤维化诊断标志物。现有的直接（血清）标志物和间接标志物（基于血液指标等参数建立的模型）在排除性诊断方面具有方便、安全、可重复等优势。基于国内外相关指南共识和多中心研究结果以及上海地区的质量调查结果，上海中医药大学附属岳阳中西医结合医院等机构制定《肝纤维化非创伤性实验诊断专家共识》，就肝纤维化非创伤性实验诊断的临床意义、适用人群、结果解读、检测方法、质量控制和前沿进展等提出建议，以期科学、合理地应用非创伤性肝纤维化标志物，从而更好地辅助临床进行多种肝病相关肝纤维化的诊断、病程监测和疗效评估。

关键词: 肝纤维化, 诊断, 直接标志物, 间接标志物

Abstract:

Hepatic fibrosis is a pathological repair response of the liver to various chronic injuries. Early diagnosis and intervention can stop or even reverse hepatic fibrosis. Currently，there remains the lack of specific biomarkers for hepatic fibrosis in clinical practice. Existing direct（serum）biomarkers and indirect biomarkers（the models established based on hematological parameters）hold significant value in exclusion diagnosis，offering advantages such as convenience，safety and repeatability. Based on relevant international and Chinese guidelines or expert consensus statements，multicenter research findings and regional quality surveys in Shanghai，Yueyang Hospital of Integrated Traditional Chinese and Western Medicine of Shanghai University of Traditional Chinese Medicine in collaboration with other institutions jointly developed the Expert Consensus on Non-invasive Laboratory Diagnosis for Hepatic Fibrosis. This expert consensus address the key issues of non-invasive laboratory diagnosis for hepatic fibrosis，including the clinical implications，applicable subjects，result interpretation，determination methods，quality control and cutting-edge advancements. This expert consensus aims to assist the better understanding and scientific application of non-invasive biomarkers in the diagnosis，monitoring and therapeutic evaluation of hepatic fibrosis.

Key words: Hepatic fibrosis, Diagnosis, Direct biomarker, Indirect biomarker

中图分类号:

R575.2

上海中医药大学附属岳阳中西医结合医院上海市临床检验中心, 中国康复医学会医学检验与康复专业委员会中国中西医结合学会检验医学专业委员会, 上海市免疫学会肿瘤免疫分会上海市医学会分子诊断专科分会. 肝纤维化非创伤性实验诊断专家共识[J]. 检验医学, 2025, 40(7): 625-641.

Yueyang Hospital of Integrated Traditional Chinese and Western Medicine of Shanghai University of Traditional Chinese Medicine Shanghai Center for Clinical Laboratory, Clinical Laboratory Society of Chinese Association for Rehabilitation Medicine Clinical Laboratory Society of Chinese Association of Integrative Medicine, Tumor Immunology Branch of Shanghai Society for Immunology Molecular Diagnostics Society of Shanghai Medical Association. Expert consensus on non-invasive laboratory diagnosis for hepatic fibrosis[J]. Laboratory Medicine, 2025, 40(7): 625-641.

图/表 1

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标志物	公式	适用对象	发布机构和发布年份
APRI评分	APRI=[AST（U·L^-1）/AST（参考区间上限）×100]/PLT计数（×109L^-1）	CHC、MAFLD、CHB、WD	中华医学会肝病学分会等^[55,95]（2022年）、KASL①^[57]（2024年）、EASL②等^[93]（2024年）、AASLD③^[101-102]（2023年）、EASL^[103]（2020年）
FIB-4	FIB-4=[年龄（岁）×AST（U·L^-1）]/ [PLT计数（×109L^-1）×√ALT（U·L^-1）]	CHC、MAFLD、CHB、ALD、WD	中华医学会肝病学分会^[6]（2024年）、中华医学会肝病学分会等^[55,94]（2022年）、ACG④^[21]（2024年）、KASL^[57]（2024年）、EASL等^[93]（2024年）、AASLD^[101-102]（2023年）、AASLD等^[104]（2023年）、EASL^[103]（2020年）、EASL^[56]（2018年）、AASLD^[105]（2018年）
FibroTest模型	FibroTest=4.467×lgα2-巨球蛋白-1.357× lg触珠蛋白+1.017×lg GGT+0.028 1× 年龄（岁）+1.737×lg总胆红素-（1.184×载脂蛋白A1）+0.301×性别（男性=1，女性=0）-5.540	CHC、CHB、ALD、MAFLD	ACG^[21]（2024年）、KASL^[57]（2024年）、AASLD等^[104]（2023年）、EASL^[103]（2020年）、AASLD^[106]（2020年）、EASL^[56]（2018年）、AASLD^[105]（2018年）
NFS	NFS=-1.675+0.037×年龄（岁）+ 0.094×BMI（kg·m-2）+1.13×IFG或糖尿病（有=1，无=0）+0.99×AAR-0.013×PLT计数（×109L^-1）-0.66× 白蛋白（g·dL^-1）	MAFLD	中华医学会肝病学分会^[6]（2024年）、KASL^[57]（2024年）、EASL等^[93]（2024年）、AASLD^[101]（2023年）
GPR	GPR=[GGT/GGT参考区间上限×100]/ PLT计数（×109L^-1）	CHB	中华医学会肝病学分会等^[55]（2022年）
RPR	RPR=RDW（%）/PLT计数（×109L^-1）	CHB	中华医学会肝病学分会等^[55]（2022年）
AAR	AAR=AST（U·L^-1）/ALT（U·L^-1）	CHC、MAFLD	KASL^[57]（2024年）、EASL等^[93]（2024年）
ELF	-7.412+0.681×ln HA+0.775×ln PⅢNP+ 0.494×ln TIMP1	CHC、CHB、ALD、MAFLD、PSC	中华医学会肝病学分会^[6]（2024年）、ACG^[21]（2024年）、KASL^[57]（2024年）、EASL等^[93]（2024年）、AASLD^[101]（2023年）、AASLD等^[104]（2023年）、AASLD^[106]（2020年）、EASL^[56]（2018年）
ADAPT	exp[lg年龄（岁）×PRO-C3（ng·mL^-1）/ √PLT计数（×109L^-1）]+2型糖尿病（有=1，无=0）	MAFLD	中华医学会肝病学分会^[6]（2024年）、KASL^[57]（2024年）、EASL等^[93]（2024年）
ELFG模型	Scheuer公式:D=-014×ln 年龄+0.616× ln HA+0.586×ln PⅢNP+0.472× ln TIMP-1-6.38； Ishak公式:D=-0.08×ln 年龄+0.608× ln HA+0.601×ln PⅢNP+0.511× ln TIMP1-6.26	CHC、CHB、MASH、ALD、PBC/PSC	AASLD^[107]（2025年）
FibroSpect II	包括HA、TIMP1、α2-巨球蛋白3项指标（公式未公布）	CHC、MAFLD	AASLD^[107]（2025年）、AASLD^[101]（2023年）
Hepascore	Hepascore=Y/（l+Y），Y= exp[-4.185 818-0.024 9×年龄+0.746 4 ×性别（男性=1，女性=0）+1.003 9×α2-巨球蛋白（g/L）+0.030 2×HA（μg·L^-1）+ 0.069 1×总胆红素（μmol·L^-1）- 0.001 2×GGT（U·L^-1）]	CHC、ALD	AASLD^[107]（2025年）、KASL^[57]（2024年）
Fibroindex	1.738-0.064×PLT计数（×104/mm3）+ 0.005×AST（U·L^-1）+0.463×γ-球蛋白（g·dL^-1）	CHC	AASLD^[107]（2025年）
King's Score	年龄×AST×INR/PLT计数（×109L^-1）	CHC	AASLD^[107]（2025年）
FibroMeter	慢性病毒性肝病的公式:-0.007× PLT（g·L^-1）-0.049×凝血酶原指数（%）+0.012×AST（U·L^-1）+0.005× α2-巨球蛋白（mg·dL^-1）+0.021× HA（μg·L^-1）-0.270×尿素（mmol·L^-1）+ 0.027×年龄（岁）+3.718； ALD的公式:-0.169×凝血酶原指数（%）+0.015×α2-巨球蛋白（mg·dL^-1）+ 0.032×HA（μg·L^-1）-0.140×年龄（岁）+ 16.541	CHB、CHC、ALD	AASLD^[107]（2025年）、KASL^[57]（2024年）、EASL^[56]（2018年）
Easy Liver Fibrosis Test（Elift）	由年龄（岁）、性别、AST（U·L^-1）、GGT（U·L^-1）、PLT（g·L^-1）、PT（%）组成的评分系统	ALD、CHC、CHB、MAFLD	AASLD^[107]（2025年）
Forns index	7.811-3.131×ln PLT计数（×109L^-1）+ 0.781×ln GGT（U·L^-1）+3.467× ln 年龄（岁）-0.014×胆固醇（mg·dL^-1）	CHC、ALD	KASL^[57]（2024年）
BARD评分	AAR≥0.8=2分，BMI≥28（kg·m-2）=1分，2型糖尿病=1分	MAFLD	KASL^[57]（2024年）
FIBC3	-5.939+0.053×年龄（岁）+0.076× BMI（kg·m-2）+1.614×2型糖尿病（有=1，无=0）-0.009×PLT计数（×109L^-1）+0.071×PRO-C3（ng·mL^-1）	MAFLD	KASL^[57]（2024年）
Fibrosis Probability Index（FPI）	FPI= e/1+e；其中，*=-10.929+1.827× ln AST+0.081×年龄+0.768×饮酒史（评分为0~2分）+0.385×胰岛素抵抗指数-0.447×总胆固醇	CHC	KASL^[57]（2024年）

标志物	公式	适用对象	发布机构和发布年份
APRI评分	APRI=[AST（U·L^-1）/AST（参考区间上限）×100]/PLT计数（×109L^-1）	CHC、MAFLD、CHB、WD	中华医学会肝病学分会等^[55,95]（2022年）、KASL①^[57]（2024年）、EASL②等^[93]（2024年）、AASLD③^[101-102]（2023年）、EASL^[103]（2020年）
FIB-4	FIB-4=[年龄（岁）×AST（U·L^-1）]/ [PLT计数（×109L^-1）×√ALT（U·L^-1）]	CHC、MAFLD、CHB、ALD、WD	中华医学会肝病学分会^[6]（2024年）、中华医学会肝病学分会等^[55,94]（2022年）、ACG④^[21]（2024年）、KASL^[57]（2024年）、EASL等^[93]（2024年）、AASLD^[101-102]（2023年）、AASLD等^[104]（2023年）、EASL^[103]（2020年）、EASL^[56]（2018年）、AASLD^[105]（2018年）
FibroTest模型	FibroTest=4.467×lgα2-巨球蛋白-1.357× lg触珠蛋白+1.017×lg GGT+0.028 1× 年龄（岁）+1.737×lg总胆红素-（1.184×载脂蛋白A1）+0.301×性别（男性=1，女性=0）-5.540	CHC、CHB、ALD、MAFLD	ACG^[21]（2024年）、KASL^[57]（2024年）、AASLD等^[104]（2023年）、EASL^[103]（2020年）、AASLD^[106]（2020年）、EASL^[56]（2018年）、AASLD^[105]（2018年）
NFS	NFS=-1.675+0.037×年龄（岁）+ 0.094×BMI（kg·m-2）+1.13×IFG或糖尿病（有=1，无=0）+0.99×AAR-0.013×PLT计数（×109L^-1）-0.66× 白蛋白（g·dL^-1）	MAFLD	中华医学会肝病学分会^[6]（2024年）、KASL^[57]（2024年）、EASL等^[93]（2024年）、AASLD^[101]（2023年）
GPR	GPR=[GGT/GGT参考区间上限×100]/ PLT计数（×109L^-1）	CHB	中华医学会肝病学分会等^[55]（2022年）
RPR	RPR=RDW（%）/PLT计数（×109L^-1）	CHB	中华医学会肝病学分会等^[55]（2022年）
AAR	AAR=AST（U·L^-1）/ALT（U·L^-1）	CHC、MAFLD	KASL^[57]（2024年）、EASL等^[93]（2024年）
ELF	-7.412+0.681×ln HA+0.775×ln PⅢNP+ 0.494×ln TIMP1	CHC、CHB、ALD、MAFLD、PSC	中华医学会肝病学分会^[6]（2024年）、ACG^[21]（2024年）、KASL^[57]（2024年）、EASL等^[93]（2024年）、AASLD^[101]（2023年）、AASLD等^[104]（2023年）、AASLD^[106]（2020年）、EASL^[56]（2018年）
ADAPT	exp[lg年龄（岁）×PRO-C3（ng·mL^-1）/ √PLT计数（×109L^-1）]+2型糖尿病（有=1，无=0）	MAFLD	中华医学会肝病学分会^[6]（2024年）、KASL^[57]（2024年）、EASL等^[93]（2024年）
ELFG模型	Scheuer公式:D=-014×ln 年龄+0.616× ln HA+0.586×ln PⅢNP+0.472× ln TIMP-1-6.38； Ishak公式:D=-0.08×ln 年龄+0.608× ln HA+0.601×ln PⅢNP+0.511× ln TIMP1-6.26	CHC、CHB、MASH、ALD、PBC/PSC	AASLD^[107]（2025年）
FibroSpect II	包括HA、TIMP1、α2-巨球蛋白3项指标（公式未公布）	CHC、MAFLD	AASLD^[107]（2025年）、AASLD^[101]（2023年）
Hepascore	Hepascore=Y/（l+Y），Y= exp[-4.185 818-0.024 9×年龄+0.746 4 ×性别（男性=1，女性=0）+1.003 9×α2-巨球蛋白（g/L）+0.030 2×HA（μg·L^-1）+ 0.069 1×总胆红素（μmol·L^-1）- 0.001 2×GGT（U·L^-1）]	CHC、ALD	AASLD^[107]（2025年）、KASL^[57]（2024年）
Fibroindex	1.738-0.064×PLT计数（×104/mm3）+ 0.005×AST（U·L^-1）+0.463×γ-球蛋白（g·dL^-1）	CHC	AASLD^[107]（2025年）
King's Score	年龄×AST×INR/PLT计数（×109L^-1）	CHC	AASLD^[107]（2025年）
FibroMeter	慢性病毒性肝病的公式:-0.007× PLT（g·L^-1）-0.049×凝血酶原指数（%）+0.012×AST（U·L^-1）+0.005× α2-巨球蛋白（mg·dL^-1）+0.021× HA（μg·L^-1）-0.270×尿素（mmol·L^-1）+ 0.027×年龄（岁）+3.718； ALD的公式:-0.169×凝血酶原指数（%）+0.015×α2-巨球蛋白（mg·dL^-1）+ 0.032×HA（μg·L^-1）-0.140×年龄（岁）+ 16.541	CHB、CHC、ALD	AASLD^[107]（2025年）、KASL^[57]（2024年）、EASL^[56]（2018年）
Easy Liver Fibrosis Test（Elift）	由年龄（岁）、性别、AST（U·L^-1）、GGT（U·L^-1）、PLT（g·L^-1）、PT（%）组成的评分系统	ALD、CHC、CHB、MAFLD	AASLD^[107]（2025年）
Forns index	7.811-3.131×ln PLT计数（×109L^-1）+ 0.781×ln GGT（U·L^-1）+3.467× ln 年龄（岁）-0.014×胆固醇（mg·dL^-1）	CHC、ALD	KASL^[57]（2024年）
BARD评分	AAR≥0.8=2分，BMI≥28（kg·m-2）=1分，2型糖尿病=1分	MAFLD	KASL^[57]（2024年）
FIBC3	-5.939+0.053×年龄（岁）+0.076× BMI（kg·m-2）+1.614×2型糖尿病（有=1，无=0）-0.009×PLT计数（×109L^-1）+0.071×PRO-C3（ng·mL^-1）	MAFLD	KASL^[57]（2024年）
Fibrosis Probability Index（FPI）	FPI= e/1+e；其中，*=-10.929+1.827× ln AST+0.081×年龄+0.768×饮酒史（评分为0~2分）+0.385×胰岛素抵抗指数-0.447×总胆固醇	CHC	KASL^[57]（2024年）