自身免疫性肝炎的药物治疗进展

杨秀英; 党小红; 姜洋

doi:10.3969/j.issn.1001-5256.2023.04.026

自身免疫性肝炎的药物治疗进展

DOI: 10.3969/j.issn.1001-5256.2023.04.026

杨秀英¹,
党小红^2, , ,,
姜洋¹

1.
山西医科大学第一临床医学院，太原 030000
2.
山西医科大学第一医院消化内科，太原 030000

基金项目:

中化国际科学交流基金会 (Z2020LSXD05)

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：杨秀英负责查找文献，分析资料，文章撰写；党小红和姜洋负责文章修改和定稿。

详细信息

通信作者:
党小红, xh.Dang@163.com (ORCID: 0000-0001-6748-9638)

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- 被引次数: 0
出版历程
- 收稿日期: 2022-08-01
- 录用日期: 2022-09-01
- 出版日期: 2023-04-20

Research advances in pharmacotherapy for autoimmune hepatitis

1.
The First Clinical Medical College of Shanxi Medical University, Taiyuan 030000, China
2.
Department of Gastroenterology, The First Hospital of Shanxi Medical University, Taiyuan 030000, China

Research funding:

China Foundation for International Scientific Exchange (Z2020LSXD05)

More Information

Corresponding author: DANG Xiaohong, xh.Dang@163.com (ORCID: 0000-0001-6748-9638)

摘要

摘要: 自身免疫性肝炎是一种免疫介导的慢性炎症性肝病，目前标准治疗对大多数患者有效，对标准治疗应答不佳或不能耐受药物副作用的患者可以选择二线或三线药物治疗。随着对发病机制的深入探索，新型的治疗方法正在试验中。本文对目前自身免疫性肝炎的药物治疗研究进展作一综述。
- 肝炎, 自身免疫性 /
- 药物疗法 /
- 治疗学
Abstract: Autoimmune hepatitis (AIH) is an immune-mediated chronic inflammatory liver disease. At present, standard treatment is effective in most AIH patients, and second- or third-line pharmacotherapy can be selected for patients who have suboptimal response to standard treatment or cannot tolerate the side-effects of the drugs. Novel therapies are undergoing clinical trials with the further exploration of the pathogenesis of AIH. This article reviews the current research advances in pharmacotherapy for AIH.
- Hepatitis, Autoimmune /
- Drug Therapy /
- Therapeutics

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参考文献(45)

[1]	VERGANI D, TERZIROLI BERETTA-PICCOLI B, MIELI-VERGANI G. A reasoned approach to the treatment of autoimmune hepatitis[J]. Dig Liver Dis, 2021, 53(11): 1381-1393. DOI: 10.1016/j.dld.2021.05.033.
[2]	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.
[3]	LV T, LI M, ZENG N, et al. Systematic review and meta-analysis on the incidence and prevalence of autoimmune hepatitis in Asian, European, and American population[J]. J Gastroenterol Hepatol, 2019, 34(10): 1676-1684. DOI: 10.1111/jgh.14746.
[4]	PAPE S, SCHRAMM C, GEVERS TJ. Clinical management of autoimmune hepatitis[J]. United European Gastroenterol J, 2019, 7(9): 1156-1163. DOI: 10.1177/2050640619872408.
[5]	MACK CL, ADAMS D, ASSIS DN, 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.
[6]	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.
[7]	HARTL J, EHLKEN H, SEBODE M, et al. Usefulness of biochemical remission and transient elastography in monitoring disease course in autoimmune hepatitis[J]. J Hepatol, 2018, 68(4): 754-763. DOI: 10.1016/j.jhep.2017.11.020.
[8]	Chinese Society of Hepatology, Chinese Medical Association. Guidelines on the dagnosis 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
[9]	PAPE S, GEVERS T, VROLIJK JM, et al. High discontinuation rate of azathioprine in autoimmune hepatitis, independent of time of treatment initiation[J]. Liver Int, 2020, 40(9): 2164-2171. DOI: 10.1111/liv.14513.
[10]	PAPE S, GEVERS T, BELIAS M, et al. Predniso(lo)ne dosage and chance of remission in patients with autoimmune hepatitis[J]. Clin Gastroenterol Hepatol, 2019, 17(10): 2068-2075. e2. DOI: 10.1016/j.cgh.2018.12.035.
[11]	TANAKA A. Autoimmune hepatitis: 2019 update[J]. Gut Liver, 2020, 14(4): 430-438. DOI: 10.5009/gnl19261.
[12]	MANNS MP, WOYNAROWSKI M, KREISEL W, et al. Budesonide induces remission more effectively than prednisone in a controlled trial of patients with autoimmune hepatitis[J]. Gastroenterology, 2010, 139(4): 1198-1206. DOI: 10.1053/j.gastro.2010.06.046.
[13]	WOYNAROWSKI M, NEMETH A, BARUCH Y, et al. Budesonide versus prednisone with azathioprine for the treatment of autoimmune hepatitis in children and adolescents[J]. J Pediatr, 2013, 163(5): 1347-1353.e1. DOI: 10.1016/j.jpeds.2013.05.042.
[14]	DALEKOS GN, ARVANITI P, GATSELIS NK, et al. First results from a propensity matching trial of mycophenolate mofetil vs. azathioprine in treatment-naive AIH patients[J]. Front Immunol, 2021, 12: 798602. DOI: 10.3389/fimmu.2021.798602.
[15]	YU ZJ, ZHANG LL, HUANG TT, et al. Comparison of mycophenolate mofetil with standard treatment for autoimmune hepatitis: a meta-analysis[J]. Eur J Gastroenterol Hepatol, 2019, 31(7): 873-877. DOI: 10.1097/MEG.0000000000001367.
[16]	ROBERTS SK, LIM R, STRASSER S, et al. Efficacy and safety of mycophenolate mofetil in patients with autoimmune hepatitis and suboptimal outcomes after standard therapy[J]. Clin Gastroenterol Hepatol, 2018, 16(2): 268-277. DOI: 10.1016/j.cgh.2017.09.063.
[17]	SANTIAGO P, SCHWARTZ I, TAMARIZ L, et al. Systematic review with meta-analysis: mycophenolate mofetil as a second-line therapy for autoimmune hepatitis[J]. Aliment Pharmacol Ther, 2019, 49(7): 830-839. DOI: 10.1111/apt.15157.
[18]	DESWAL S, SRIVASTAVA A. Role of allopurinol in optimizing thiopurine therapy in patients with autoimmune hepatitis: A review[J]. J Clin Exp Hepatol, 2017, 7(1): 55-62. DOI: 10.1016/j.jceh.2017.01.115.
[19]	CZAJA AJ, CARPENTER HA. Thiopurine methyltransferase deficiency and azathioprine intolerance in autoimmune hepatitis[J]. Dig Dis Sci, 2006, 51(5): 968-975. DOI: 10.1007/s10620-006-9336-5.
[20]	de BOER YS, van GERVEN NM, de BOER NK, et al. Allopurinol safely and effectively optimises thiopurine metabolites in patients with autoimmune hepatitis[J]. Aliment Pharmacol Ther, 2013, 37(6): 640-646. DOI: 10.1111/apt.12223.
[21]	AL-SHAMMA S, MCCRUDDEN R, MCLAUGHLIN S. Letter: allopurinol co-therapy is safe and effective in autoimmune hepatitis[J]. Aliment Pharmacol Ther, 2013, 37(9): 919. DOI: 10.1111/apt.12285.
[22]	HVBENER S, OO YH, THAN NN, et al. Efficacy of 6-mercaptopurine as second-line treatment for patients with autoimmune hepatitis and azathioprine intolerance[J]. Clin Gastroenterol Hepatol, 2016, 14(3): 445-453. DOI: 10.1016/j.cgh.2015.09.037.
[23]	DOYCHEVA I, WATT KD, GULAMHUSEIN AF. Autoimmune hepatitis: Current and future therapeutic options[J]. Liver Int, 2019, 39(6): 1002-1013. DOI: 10.1111/liv.14062.
[24]	van den BRAND FF, van NIEUWKERK C, VERWER BJ, et al. Biochemical efficacy of tioguanine in autoimmune hepatitis: a retrospective review of practice in the Netherlands[J]. Aliment Pharmacol Ther, 2018, 48(7): 761-767. DOI: 10.1111/apt.14939.
[25]	LEGUÉ C, LEGROS L, KAMMERER-JACQUET S, et al. Safety and efficacy of 6-thioguanine as a second-line treatment for autoimmune hepatitis[J]. Clin Gastroenterol Hepatol, 2018, 16(2): 290-291. DOI: 10.1016/j.cgh.2017.07.032.
[26]	ROBERTS SK, STRASSER SI, NICOLL AJ, et al. Efficacy and safety profile of calcineurin inhibitor salvage therapy in autoimmune hepatitis[J]. Scand J Gastroenterol, 2020, 55(11): 1309-1317. DOI: 10.1080/00365521.2020.1821764.
[27]	NOGUCHI F, CHU PS, TANIKI N, et al. Long-term observation of cyclosporine as second-line therapy in adults for severe acute autoimmune hepatitis[J]. Hepatology, 2021, 73(6): 2594-2597. DOI: 10.1002/hep.31597.
[28]	CUARTEROLO ML, CIOCCA M, LÓPEZ S, et al. Autoimmune hepatitis in children: prednisone plus azathioprine versus cyclosporine: A randomized trial[J]. J Pediatr Gastroenterol Nutr, 2020, 71(3): 376-380. DOI: 10.1097/MPG.0000000000002776.
[29]	NASTASIO S, SCIVERES M, MATARAZZO L, et al. Long-term follow-up of children and young adults with autoimmune hepatitis treated with cyclosporine[J]. Dig Liver Dis, 2019, 51(5): 712-718. DOI: 10.1016/j.dld.2018.10.018.
[30]	ZIZZO AN, VALENTINO PL, SHAH PS, et al. Second-line agents in pediatric patients with autoimmune hepatitis: A systematic review and meta-analysis[J]. J Pediatr Gastroenterol Nutr, 2017, 65(1): 6-15. DOI: 10.1097/MPG.0000000000001530.
[31]	FERRE-ARACIL C, RIVEIRO-BARCIELA M, TRAPERO-MARUGÁN M, et al. Tacrolimus as an effective and durable second-line treatment for chronic autoimmune hepatitis: A multicentric study[J]. Dig Dis Sci, 2021, 66(8): 2826-2832. DOI: 10.1007/s10620-020-06569-9.
[32]	ABDOLLAHI M, EKRAMI NK, GHOJAZADEH M, et al. Tacrolimus and mycophenolate mofetil as second-line treatment in autoimmune hepatitis: Is the evidence of sufficient quality to develop recommendations?[J]. World J Gastroenterol, 2020, 26(38): 5896-5910. DOI: 10.3748/wjg.v26.i38.5896.
[33]	HARIDY J, NICOLL A, SOOD S. Methotrexate therapy for autoimmune hepatitis[J]. Clin Gastroenterol Hepatol, 2018, 16(2): 288-289. DOI: 10.1016/j.cgh.2017.07.003.
[34]	CHANG C, TANAKA A, BOWLUS C, et al. The use of biologics in the treatment of autoimmune liver disease[J]. Expert Opin Investig Drugs, 2020, 29(4): 385-398. DOI: 10.1080/13543784.2020.1733527.
[35]	WEILER-NORMANN C, SCHRAMM C, QUAAS A, et al. Infliximab as a rescue treatment in difficult-to-treat autoimmune hepatitis[J]. J Hepatol, 2013, 58(3): 529-534. DOI: 10.1016/j.jhep.2012.11.010.
[36]	THAN NN, HODSON J, SCHMIDT-MARTIN D, et al. Efficacy of rituximab in difficult-to-manage autoimmune hepatitis: Results from the International Autoimmune Hepatitis Group[J]. JHEP Rep, 2019, 1(6): 437-445. DOI: 10.1016/j.jhepr.2019.10.005.
[37]	ARVANITI P, GIANNOULIS G, GABETA S, et al. Belimumab is a promising third-line treatment option for refractory autoimmune hepatitis[J]. JHEP Rep, 2020, 2(4): 100123. DOI: 10.1016/j.jhepr.2020.100123.
[38]	CHATRATH H, ALLEN L, BOYER TD. Use of sirolimus in the treatment of refractory autoimmune hepatitis[J]. Am J Med, 2014, 127(11): 1128-1131. DOI: 10.1016/j.amjmed.2014.06.016.
[39]	YTTING H, LARSEN FS. Everolimus treatment for patients with autoimmune hepatitis and poor response to standard therapy and drug alternatives in use[J]. Scand J Gastroenterol, 2015, 50(8): 1025-1031. DOI: 10.3109/00365521.2014.998271.
[40]	CZAJA AJ. Exploring the pathogenic role and therapeutic implications of interleukin 2 in autoimmune hepatitis[J]. Dig Dis Sci, 2021, 66(8): 2493-2512. DOI: 10.1007/s10620-020-06562-2.
[41]	SAADOUN D, ROSENZWAJG M, JOLY F, et al. Regulatory T-cell responses to low-dose interleukin-2 in HCV-induced vasculitis[J]. N Engl J Med, 2011, 365(22): 2067-2077. DOI: 10.1056/NEJMoa1105143.
[42]	TODO S, YAMASHITA K, GOTO R, et al. A pilot study of operational tolerance with a regulatory T-cell-based cell therapy in living donor liver transplantation[J]. Hepatology, 2016, 64(2): 632-643. DOI: 10.1002/hep.28459.
[43]	O'BRIEN CB, BARNEA ER, MARTIN P, et al. Randomized, double-blind, placebo-controlled, single ascending dose trial of synthetic preimplantation factor in autoimmune hepatitis[J]. Hepatol Commun, 2018, 2(10): 1235-1246. DOI: 10.1002/hep4.1239.
[44]	XIANG M, LIU T, TAN W, et al. Effects of kinsenoside, a potential immunosuppressive drug for autoimmune hepatitis, on dendritic cells/CD8⁺ T cells communication in mice[J]. Hepatology, 2016, 64(6): 2135-2150. DOI: 10.1002/hep.28825.
[45]	S'WIERCZEK A, POMIERNY B, WYSKA E, et al. Pharmacokinetic/pharmacodynamic assessment of selective phosphodiesterase inhibitors in a mouse model of autoimmune hepatitis[J]. J Pharmacol Exp Ther, 2022, 381(2): 151-163. DOI: 10.1124/jpet.121.001004.