Section of Hepatology, Hepatology Services, Rush University Medical Center, Chicago, Illinois, USA.
Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Hepatol Commun. 2024 Jun 5;8(6). doi: 10.1097/HC9.0000000000000458. eCollection 2024 Jun 1.
Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that can lead to cirrhosis and liver failure. AIH can present in all ages, races, and ethnicities, but it predominantly affects women. As a heterogeneous disease, AIH presents variably in different patients, making diagnosis and treatment a challenge. Currently, the standard treatment for AIH comprises immunosuppressants; however, their long-term use is associated with adverse effects. The pathogenesis of AIH is complex, involving T cells, macrophages, and plasma cells that invade the periportal parenchyma and lead to an inflammatory cascade that can result in liver damage. Due to the complexity of AIH pathogenesis, treatment targets several inflammatory pathways. However, unlike other autoimmune diseases in which targeted treatments have been approved, there has been little progress made in advancing the treatment paradigm for AIH. Major obstacles to progress include challenges in conducting clinical trials, particularly patient recruitment and ensuring a diverse range of backgrounds; poorly defined outcomes to assess treatment response and improved quality of life; and a lack of study designs that account for the stage of disease and variations in treatment. A focus on individualized and steroid-free treatment approaches is needed to improve AIH prognosis and minimize steroid-associated adverse effects.
自身免疫性肝炎(AIH)是一种慢性炎症性肝病,可导致肝硬化和肝衰竭。AIH 可发生于所有年龄段、种族和民族,但主要影响女性。作为一种异质性疾病,AIH 在不同患者中的表现各不相同,这使得诊断和治疗具有挑战性。目前,AIH 的标准治疗包括免疫抑制剂;然而,它们的长期使用与不良反应有关。AIH 的发病机制复杂,涉及到 T 细胞、巨噬细胞和浆细胞,它们侵犯门脉周围实质,导致炎症级联反应,从而导致肝损伤。由于 AIH 发病机制复杂,治疗靶点涉及多个炎症途径。然而,与其他已批准靶向治疗的自身免疫性疾病不同,AIH 的治疗模式几乎没有取得进展。进展的主要障碍包括临床试验的开展面临挑战,特别是患者招募和确保多样化背景;治疗反应和提高生活质量的评估结果定义不明确;缺乏考虑疾病阶段和治疗变化的研究设计。需要关注个体化和无类固醇治疗方法,以改善 AIH 的预后并最小化类固醇相关的不良反应。