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自身免疫性肝炎治疗的演变

Evolution of Therapy in Autoimmune Hepatitis.

作者信息

Ergenc Ilkay, Frolkis Alexandra, Chung Yooyun, Heneghan Michael A

机构信息

1Institute of Liver Studies, King's College Hospital, London, United Kingdom.

2School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom.

出版信息

Gastroenterol Hepatol (N Y). 2025 Mar;21(3):152-160.

Abstract

Autoimmune hepatitis (AIH) is an immune-mediated liver disease characterized by a spectrum of clinical manifestations, ranging from asymptomatic liver enzyme abnormalities to fulminant liver failure. Despite significant achievements, the backbone of first-line AIH treatment, including corticosteroids and azathioprine, has remained nearly unchanged for 5 decades. However, up to 20% of patients experience insufficient response, loss of response, or treatment intolerance. For patients intolerant to first-line therapy, second-line options include mercaptopurine and mycophenolate mofetil (MMF), with recent debates regarding MMF's potential role in first-line treatment. A significant advancement has been the tailoring of azathioprine doses and manipulating blood levels with the addition of low-dose allopurinol by using therapeutic metabolite monitoring for patients with insufficient or lost biochemical response. Increasing experience with calcineurin inhibitors and biologic agents, particularly rituximab and infliximab, has demonstrated their efficacy as third-line options. Notably, B-cell activating factor blockade emerges as a promising future treatment. This article delves into the chronological evolution of AIH treatment, focusing on recent advances.

摘要

自身免疫性肝炎(AIH)是一种免疫介导的肝脏疾病,其临床表现多样,从无症状的肝酶异常到暴发性肝衰竭不等。尽管取得了重大进展,但包括皮质类固醇和硫唑嘌呤在内的一线AIH治疗的主要药物在近50年里几乎没有变化。然而,高达20%的患者疗效不佳、出现疗效丧失或不耐受治疗。对于不耐受一线治疗的患者,二线选择包括巯嘌呤和霉酚酸酯(MMF),近期对于MMF在一线治疗中的潜在作用存在争议。一项重大进展是通过对生化反应不足或丧失的患者进行治疗性代谢物监测,调整硫唑嘌呤剂量并加用低剂量别嘌醇来控制血药浓度。对钙调神经磷酸酶抑制剂和生物制剂,特别是利妥昔单抗和英夫利昔单抗的经验不断积累,已证明它们作为三线治疗方案的有效性。值得注意的是,B细胞活化因子阻断剂成为一种有前景的未来治疗方法。本文深入探讨了AIH治疗的时间演变,重点关注近期进展。

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