自身免疫性肝炎相关自身抗原抗体的再梳理

闫惠平; 张海萍

doi:10.12449/JCH260928

自身免疫性肝炎相关自身抗原抗体的再梳理

DOI: 10.12449/JCH260928

闫惠平^{1, 2, , ,},
张海萍¹

1.
首都医科大学附属北京佑安医院临床检验中心，北京 100069
2.
首都医科大学附属北京佑安医院肝病中心二科，北京 100069

基金项目:

国家卫生健康委员会医药科技发展研究中心 (28-5-5);

首都医科大学附属北京佑安医院2021年院内中青年人才孵育项目（青年创新类） (YNKTQN2021004)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：闫惠平负责设计思路、部分论文的撰写和修改定稿；张海萍负责查阅文献、核实数据并撰写部分论文。

详细信息

通信作者:
闫惠平， yhp503@126.com （ORCID： 0000-0001-5980-7675）

计量
- 文章访问数: 11
- HTML全文浏览量: 8
- PDF下载量: 0
- 被引次数: 0
出版历程
- 收稿日期: 2026-01-13
- 录用日期: 2026-04-02
- 出版日期: 2026-09-25

Autoantigens and autoantibodies associated with autoimmune hepatitis

Huiping Yan^{1, 2
, ,
,},
Haiping Zhang¹

1.
Clinical Laboratory Center，Beijing YouAn Hospital，Capital Medical University，Beijing 100069，China
2.
Second Department of Liver Disease Center，Beijing YouAn Hospital，Capital Medical University，Beijing 100069，China

Research funding:

National Health Commission Medical Science and Technology Development Research Center (28-5-5);

Young and Middle-Aged Talent Incubation Project in Beijing YouAn Hospital, Capital Medical University （2021， Youth Innovation） (YNKTQN2021004)

More Information

Corresponding author: Yan Huiping， yhp503@126.com （ORCID： 0000-0001-5980-7675）

摘要

摘要: 自身免疫性肝炎（AIH）是一类由针对肝细胞的自身免疫反应介导的肝实质炎症，自身抗体是AIH临床诊断的关键标志物之一。本文结合2025年欧洲肝病学会与英国胃肠病学会新发布的AIH临床指南，对指南中关于AIH分型、抗核抗体检测方法以及简化评分标准适用性的推荐建议进行介绍，并系统梳理AIH相关自身抗体的靶抗原特征，及其在AIH诊断、治疗与病情评估等环节中的作用。本文指出，探索新型特异性生物标志物是当前AIH研究领域亟待解决的问题。
- 肝炎，自身免疫性 /
- 自身抗体 /
- 抗原
Abstract: Autoimmune hepatitis （AIH） is a type of liver parenchymal inflammation mediated by an autoimmune response targeting hepatocytes， and autoantibodies are one of the key biomarkers for the clinical diagnosis of AIH. With reference to the new guidelines for AIH released by the European Association for the Study of the Liver and the British Society of Gastroenterology in 2025， this article introduces the recommendations for AIH subtyping， anti-nuclear antibody detection methods， and applicability of simplified scoring criteria and systematically reviews the characteristics of target antigens of autoantibodies associated with AIH and their roles in the diagnosis， treatment， and disease assessment of AIH. It also points out that identifying new specific biomarkers is an urgent issue in AIH research.
- Hepatitis， Autoimmune /
- Autoantibodies /
- Antigens

HTML全文

表 1 血清学更新的AIH简化诊断标准^［12］

Table 1. Simplified criteria of AIH： Update of serologic criteria^［12］

变量	阈值	分值^1）
ANA或ASMA/F-actin	阳性^2）	1
ANA或ASMA/F-actin	强阳性^3）	2
或抗-LKM-1	≥1∶40	2
或抗-SLA	阳性	2
IgG	正常值上限	1
IgG	>1.1倍正常值上限	2
肝组织学（有肝炎证据）	符合AIH	1
肝组织学（有肝炎证据）	典型AIH表现	2
排除病毒性肝炎	是	2
注：1）自身抗体最高可获2分；2）间接免疫荧光法检测ANA：基于组织切片≥1∶40，基于HEp-2细胞≥1∶80或1∶160或根据当地标准，酶联免疫吸附测定依据当地检测界限值；3）间接免疫荧光法检测ANA：基于组织切片≥1∶80，基于HEp-2细胞≥1∶160或1∶320，酶联免疫吸附测定依据当地检测界限值。若临床高度怀疑AIH但酶联免疫吸附测定检测自身抗体阴性，应采用间接免疫荧光法检测。总分≥6分提示可能存在AIH；总分≥7分提示确诊AIH。ANA，抗核抗体；ASMA，抗平滑肌抗体；F-actin，F-肌动蛋白；抗-LKM-1，抗肝肾微粒体抗体1；抗-SLA，抗可溶性肝抗原；IgG，免疫球蛋白G；AIH，自身免疫性肝炎。

下载: 导出CSV

参考文献(49)

[1]	European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the management of autoimmune hepatitis[J]. J Hepatol, 2025, 83( 2): 453- 501. DOI: 10.1016/j.jhep.2025.03.017.
[2]	Alvarez F, Berg P A, Bianchi F B, et al. International Autoimmune Hepatitis Group Report: Review of criteria for diagnosis of autoimmune hepatitis[J]. J Hepatol, 1999, 31( 5): 929- 938. DOI: 10.1016/s0168-8278(99)80297-9.
[3]	Hennes E M, Zeniya M, Czaja A J, et al. Simplified criteria for the diagnosis of autoimmune hepatitis[J]. Hepatology, 2008, 48( 1): 169- 176. DOI: 10.1002/hep.22322.
[4]	Chinese Society of Hepatology, Chinese Medical Association. Guidelines on the diagnosis and management of autoimmune hepatitis(2021)[J]. J Clin Hepatol, 2022, 38( 1): 42- 49. DOI: 10.3760/cma.j.cn112138-20211112-00796. 中华医学会肝病学分会. 自身免疫性肝炎诊断和治疗指南(2021)[J]. 临床肝胆病杂志, 2022, 38( 1): 42- 49. DOI: 10.3760/cma.j.cn112138-20211112-00796.
[5]	Gleeson D, Bornand R, Brownlee A, et al. British Society of Gastroenterology guidelines for diagnosis and management of autoimmune hepatitis[J]. Gut, 2025, 74( 9): 1364- 1409. DOI: 10.1136/gutjnl-2024-333171.
[6]	Shoenfeld Y, Gershwin M E, Meroni P L. Autoantibodies[M]. 2^nd ed. Amsterdam: Elsevier Science, 2007.
[7]	The Committee of the Autoantibodies Detection of Rheumatology and Innunology Physicians Committee of Chinese Medical Doctor Association. Experts consensus on the clinical application of antinuclear antibodies detection[J]. Chin J Lab Med, 2018, 41( 4): 275- 280. DOI: 10.3760/cma.j.issn.1009-9158.2018.04.008. 中国医师协会风湿免疫科医师分会自身抗体检测专业委员会. 抗核抗体检测的临床应用专家共识[J]. 中华检验医学杂志, 2018, 41( 4): 275- 280. DOI: 10.3760/cma.j.issn.1009-9158.2018.04.008.
[8]	Yan Huiping, Jia Jidong. Autoimmune liver diseases[M]. Beijing: People’s Medical Publishing House, 2018. 闫惠平, 贾继东. 自身免疫性肝脏疾病[M]. 北京: 人民卫生出版社, 2018.
[9]	Vergani D, Alvarez F, Bianchi F B, et al. Liver autoimmune serology: A consensus statement from the committee for autoimmune serology of the International Autoimmune Hepatitis Group[J]. J Hepatol, 2004, 41( 4): 677- 683. DOI: 10.1016/j.jhep.2004.08.002.
[10]	Task Force of Clinical Immunology Committee of Chinese Society for Immunology. Recommendation for methodology of autoantibody detection in autoimmune disease[J]. Chin J Lab Med, 2020, 43( 9): 878- 888. DOI: 10.3760/cma.j.cn114452-20191225-00750. 中国免疫学会临床免疫分会专家组. 自身免疫病诊断中抗体检测方法的推荐意见[J]. 中华检验医学杂志, 2020, 43( 9): 878- 888. DOI: 10.3760/cma.j.cn114452-20191225-00750.
[11]	European Association for the Study of the Liver. EASL clinical practice guidelines: Autoimmune hepatitis[J]. J Hepatol, 2015, 63( 4): 971- 1004. DOI: 10.1016/j.jhep.2015.06.030.
[12]	Galaski J, Weiler-Normann C, Schakat M, et al. Update of the simplified criteria for autoimmune hepatitis: Evaluation of the methodology for immunoserological testing[J]. J Hepatol, 2021, 74( 2): 312- 320. DOI: 10.1016/j.jhep.2020.07.032.
[13]	Muratori L, Lohse A W, Lenzi M. Diagnosis and management of autoimmune hepatitis[J]. BMJ, 2023, 380: e070201. DOI: 10.1136/bmj-2022-070201.
[14]	Terziroli Beretta-Piccoli B, Mieli-Vergani G, Vergani D. Autoimmmune hepatitis[J]. Cell Mol Immunol, 2022, 19( 2): 158- 176. DOI: 10.1038/s41423-021-00768-8.
[15]	Andrade L E C, Klotz W, Herold M, et al. Reflecting on a decade of the international consensus on ANA patterns(ICAP): Accomplishments and challenges from the perspective of the 7th ICAP workshop[J]. Autoimmun Rev, 2024, 23( 9): 103608. DOI: 10.1016/j.autrev.2024.103608.
[16]	Yang Bin, Hu Chaojun. Illustration of antinuclear antibodies: Fluorescence model recognition and case selection[M]. Beijing: People’s Medical Publishing House, 2024. 杨滨, 胡朝军. 图说抗核抗体: 荧光模型识别与病例精选[M]. 北京: 人民卫生出版社, 2024.
[17]	The Committee of the Autoantibodies Detection of Rheumatology and Immunology Physicians Committee of Chinese Medical Doctor Association, Chinese Rheumatism Data Center, National Clinical Research Center for Dermatologic and Immunologic Diseases. Expert consensus on clinical application of autoantibodies detection in patients with autoimmune liver disease[J]. Chin J Intern Med, 2021, 60( 7): 619- 625. DOI: 10.3760/cma.j.cn112138-20210114-00037. 中国医师协会风湿免疫科医师分会自身抗体检测专业委员会, 国家风湿病数据中心, 国家皮肤与免疫疾病临床医学研究中心. 自身免疫性肝病相关自身抗体检测的临床应用专家共识[J]. 中华内科杂志, 2021, 60( 7): 619- 625. DOI: 10.3760/cma.j.cn112138-20210114-00037.
[18]	Mack C L, Adams D, Assis D N, et al. Diagnosis and management of autoimmune hepatitis in adults and children: 2019 practice guidance and guidelines from the American association for the study of liver diseases[J]. Hepatology, 2020, 72( 2): 671- 722. DOI: 10.1002/hep.31065.
[19]	Dalekos G N, Gatselis N K. Autoimmune serology testing in clinical practice: An updated roadmap for the diagnosis of autoimmune hepatitis[J]. Eur J Intern Med, 2023, 108: 9- 17. DOI: 10.1016/j.ejim.2022.11.013.
[20]	Li Y, Yan L, Wang R, et al. Serum immunoglobulin G levels predict biochemical and histological remission of autoimmune hepatitis type 1: A single-center experience and literature review[J]. Clin Rev Allergy Immunol, 2022, 62( 2): 292- 300. DOI: 10.1007/s12016-021-08833-w.
[21]	Mieli-Vergani G, Vergani D, Czaja A J, et al. Autoimmune hepatitis[J]. Nat Rev Dis Primers, 2018, 4: 18017. DOI: 10.1038/nrdp.2018.17.
[22]	Terziroli Beretta-Piccoli B, Mieli-Vergani G, Vergani D. Autoimmune hepatitis: Serum autoantibodies in clinical practice[J]. Clin Rev Allergy Immunol, 2022, 63( 2): 124- 137. DOI: 10.1007/s12016-021-08888-9.
[23]	Gambino C M, Agnello L, Calvaruso V, et al. Prevalence and heterogeneity of antinuclear antibody patterns in adult Italian patients with autoimmune liver diseases: Our experience[J]. Clin Chim Acta, 2025, 566: 120037. DOI: 10.1016/j.cca.2024.120037.
[24]	Tanaka A, Ma X, Takahashi A, et al. Primary biliary cholangitis[J]. Lancet, 2024, 404( 10457): 1053- 1066. DOI: 10.1016/S0140-6736(24)01303-5.
[25]	Bottazzo G F, Florin-Christensen A, Fairfax A, et al. Classification of smooth muscle autoantibodies detected by immunofluorescence[J]. J Clin Pathol, 1976, 29( 5): 403- 410. DOI: 10.1136/jcp.29.5.403.
[26]	Katsumi T, Ueno Y. Epidemiology and surveillance of autoimmune hepatitis in Asia[J]. Liver Int, 2022, 42( 9): 2015- 2022. DOI: 10.1111/liv.15155.
[27]	Granito A, Muratori P, Pappas G, et al. Easy recognition and high autoimmune hepatitis specificity of smooth muscle antibodies giving an actin microfilament immunofluorescent pattern on embryonal vascular smooth muscle cells[J]. Clin Exp Immunol, 2024, 217( 3): 233- 239. DOI: 10.1093/cei/uxae051.
[28]	Zhang H P, Ma Y X, Li L J, et al. Performance of F-actin IgG ELISA in Chinese patients with autoimmune hepatitis(AIH) and autoimmune hepatitis/primary biliary cholangitis overlap(AIH/PBC)[J]. Hepatol Int, 2017, 11( Suppl 1): S578.
[29]	Couto C A, Bittencourt P L, Porta G, et al. Antismooth muscle and antiactin antibodies are indirect markers of histological and biochemical activity of autoimmune hepatitis[J]. Hepatology, 2014, 59( 2): 592- 600. DOI: 10.1002/hep.26666.
[30]	Shibuki T, Otsuka T, Isoda H, et al. Seropositivity and titers of anti-smooth muscle actin antibody are associated with relapse of type 1 autoimmune hepatitis[J]. Med Sci Monit, 2017, 23: 4028- 4033. DOI: 10.12659/msm.902576.
[31]	Manns M, Gerken G, Kyriatsoulis A, et al. Characterisation of a new subgroup of autoimmune chronic active hepatitis by autoantibodies against a soluble liver antigen[J]. Lancet, 1987, 1( 8528): 292- 294. DOI: 10.1016/s0140-6736(87)92024-1.
[32]	Wies I, Brunner S, Henninger J, et al. Identification of target antigen for SLA/LP autoantibodies in autoimmune hepatitis[J]. Lancet, 2000, 355( 9214): 1510- 1515. DOI: 10.1016/s0140-6736(00)02166-8.
[33]	Kramer M, Mele F, Jovic S, et al. Clonal analysis of SepSecS-specific B and T cells in autoimmune hepatitis[J]. J Clin Invest, 2025, 135( 2): e183776. DOI: 10.1172/JCI183776.
[34]	Zhang Haiping, Ma Yinxue, Li Lijuan, et al. Analysis of the autoantibodies characteristics of 77 anti-soluble liver antigen positive patients with liver diseases[J]. Chin J Lab Med, 2019, 42( 11): 927- 932. DOI: 10.3760/cma.j.issn.1009-9158.2019.11.007. 张海萍, 马胤雪, 李丽娟, 等. 77例抗可溶性肝抗原抗体阳性肝病患者的自身抗体特征分析[J]. 中华检验医学杂志, 2019, 42( 11): 927- 932. DOI: 10.3760/cma.j.issn.1009-9158.2019.11.007.
[35]	Zhang H P, Liu Y M, Li Z, et al. Clinical characteristics and HLA genotypes in Chinese patients with anti-SLA/LP-positive autoimmune hepatitis[J]. Ann Transl Med, 2021, 9( 2): 153. DOI: 10.21037/atm-20-8036.
[36]	Zachou K, Gampeta S, Gatselis N K, et al. Anti-SLA/LP alone or in combination with anti-Ro52 and fine specificity of anti-Ro52 antibodies in patients with autoimmune hepatitis[J]. Liver Int, 2015, 35( 2): 660- 672. DOI: 10.1111/liv.12658.
[37]	Czaja A J. Examining pathogenic concepts of autoimmune hepatitis for cues to future investigations and interventions[J]. World J Gastroenterol, 2019, 25( 45): 6579- 6606. DOI: 10.3748/wjg.v25.i45.6579.
[38]	Zhang Haiping, Yan Huiping, Chen Dexi, et al. The role of pathogen infections in the development and progression of autoimmune liver diseases[J]. J Clin Hepatol, 2022, 38( 4): 754- 758. DOI: 10.3969/j.issn.1001-5256.2022.04.004. 张海萍, 闫惠平, 陈德喜, 等. 病原感染在自身免疫性肝病发生发展中的作用[J]. 临床肝胆病杂志, 2022, 38( 4): 754- 758. DOI: 10.3969/j.issn.1001-5256.2022.04.004.
[39]	Warner S, Rajanayagam J, Russell E, et al. Biliary disease progression in childhood onset autoimmune liver disease: A 30-year follow-up into adulthood[J]. JHEP Rep, 2024, 6( 2): 100901. DOI: 10.1016/j.jhepr.2023.100901.
[40]	Han Ying, Yan Huiping, Liao Huiyu, et al. Clinical value of anti-liver/kidney microsomal-1 antibody in patients with liver disease[J]. Chin J Hepatol, 2017, 25( 11): 852- 857. DOI: 10.3760/cma.j.issn.1007-3418.2017.11.010. 韩莹, 闫惠平, 廖慧钰, 等. 抗肝肾微粒体抗体在肝病患者中的临床意义评价[J]. 中华肝脏病杂志, 2017, 25( 11): 852- 857. DOI: 10.3760/cma.j.issn.1007-3418.2017.11.010.
[41]	Martini E, Abuaf N, Cavalli F, et al. Antibody to liver cytosol(anti-LC1) in patients with autoimmune chronic active hepatitis type 2[J]. Hepatology, 1988, 8( 6): 1662- 1666. DOI: 10.1002/hep.1840080632.
[42]	Lapierre P, Hajoui O, Homberg J C, et al. Formiminotransferase cyclodeaminase is an organ-specific autoantigen recognized by sera of patients with autoimmune hepatitis[J]. Gastroenterology, 1999, 116( 3): 643- 649. DOI: 10.1016/s0016-5085(99)70186-1.
[43]	Renous R, Lapierre P, Djilali-Saiah I, et al. Characterization of the antigenicity of the formiminotransferase-cyclodeaminase in type 2 autoimmune hepatitis[J]. Exp Cell Res, 2004, 292( 2): 332- 341. DOI: 10.1016/j.yexcr.2003.09.009.
[44]	Terziroli Beretta-Piccoli B, Ripellino P, Gobbi C, et al. Autoimmune liver disease serology in acute hepatitis E virus infection[J]. J Autoimmun, 2018, 94: 1- 6. DOI: 10.1016/j.jaut.2018.07.006.
[45]	Santos B C, Guedes L R, Faria L C, et al. Wilson’s disease presentation resembling autoimmune hepatitis[J]. BMJ Case Rep, 2019, 12( 10): e230721. DOI: 10.1136/bcr-2019-230721.
[46]	Zhang Haiping, Yan Huiping, Lou Jinli, et al. Characteristics of clinical and laboratory indexes in patients with liver disease with positive anti-liver cytosol antibody[J]. Chin J Hepatol, 2021, 29( 12): 1182- 1187. DOI: 10.3760/cma.j.cn501113-20210106-00009. 张海萍, 闫惠平, 娄金丽, 等. 抗肝细胞溶质抗原1型抗体阳性肝病患者的临床及实验室指标特征[J]. 中华肝脏病杂志, 2021, 29( 12): 1182- 1187. DOI: 10.3760/cma.j.cn501113-20210106-00009.
[47]	Taubert R, Engel B, Diestelhorst J, et al. Quantification of polyreactive immunoglobulin G facilitates the diagnosis of autoimmune hepatitis[J]. Hepatology, 2022, 75( 1): 13- 27. DOI: 10.1002/hep.32134.
[48]	Abe K, Jun W D, Hayashi M, et al. Identification of anti-DOK2 antibodies in patients with autoimmune hepatitis via a human protein microarray[J]. Hepatol Commun, 2025, 9( 10): e0807. DOI: 10.1097/HC9.0000000000000807.
[49]	Yan Huiping, Liu Yanmin, Zhang Haiping. Review and prospect of the development in the field of autoimmune liver diseases in China over the last 20 years[J]. J Clin Hepatol, 2022, 38( 4): 737- 742. DOI: 10.3969/j.issn.1001-5256.2022.04.001. 闫惠平, 刘燕敏, 张海萍. 近二十年我国自身免疫性肝病领域发展历程的回顾与展望[J]. 临床肝胆病杂志, 2022, 38( 4): 737- 742. DOI: 10.3969/j.issn.1001-5256.2022.04.001.