Department of Surgery, Oncology and Gastroenterology-DiSCOG, University of Padova, Via Giustiniani 2, 35128, Padova, Italy.
Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia.
J Autoimmun. 2018 Dec;95:133-143. doi: 10.1016/j.jaut.2018.10.020. Epub 2018 Oct 29.
Autoimmune hepatitis is a chronic inflammatory liver disease characterized by hypergammaglobulinemia, the presence of autoantibodies, and inflammation within the liver, including lymphocytic infiltrates and interface hepatitis. Autoimmune hepatitis shows a female predominance and can present at any age and in any ethnicity. The disease is thought to be a consequence of a break of immune tolerance leading to an autoimmune process that induces liver injury. The self-attack is triggered by T-helper cell-mediated liver autoantigen recognition and B-cell production of autoantibodies, and is sustained by impaired regulatory T cells number and function. Superimposed on a genetic predisposition, infections and environmental factors have been studied as triggering factors for the disease. Allelic variants in the HLA locus have been associated with susceptibility; associations with single nucleotide polymorphisms within non-HLA genes have also been assessed. Several factors have been described as triggers of autoimmune responses in predisposed individuals, including infections, alcohol, vitamin D deficiency, and an altered composition of the intestinal microbiome. Importantly, drugs and herbal agents may trigger classical autoimmune hepatitis, or may induce a liver disease with autoimmune features. Interactions between female hormones and genetic factors have been hypothesized to play a role in autoimmunity, although the exact role for these factors has not been fully established. Herein we present a review of the etiology of autoimmune hepatitis including de novo autoimmune hepatitis post-liver transplantation as well as animal models for its study.
自身免疫性肝炎是一种慢性炎症性肝病，其特征是高γ球蛋白血症、自身抗体的存在以及肝脏内的炎症，包括淋巴细胞浸润和界面肝炎。自身免疫性肝炎以女性为主，可发生于任何年龄和任何种族。该病被认为是免疫耐受打破导致自身免疫过程诱导肝损伤的结果。自身攻击是由 T 辅助细胞介导的肝自身抗原识别和 B 细胞产生自身抗体触发的，并由调节性 T 细胞数量和功能受损维持。在遗传易感性的基础上，感染和环境因素已被研究为疾病的触发因素。HLA 基因座的等位基因变异与易感性相关；非 HLA 基因内的单核苷酸多态性的相关性也已被评估。有几个因素被描述为易患个体自身免疫反应的触发因素，包括感染、酒精、维生素 D 缺乏和肠道微生物组的组成改变。重要的是，药物和草药制剂可能会引发典型的自身免疫性肝炎，也可能会引起具有自身免疫特征的肝病。女性激素和遗传因素之间的相互作用被假设在自身免疫中起作用，尽管这些因素的确切作用尚未完全确定。本文综述了自身免疫性肝炎的病因学，包括肝移植后新发自身免疫性肝炎以及用于其研究的动物模型。
