Paediatric Liver, GI and Nutrition Centre, MowatLabs, King's College Hospital, Denmark Hill, SE5 9RS London, UK.
Institute of Liver Studies, MowatLabs, King's College Hospital, Denmark Hill, SE5 9RS London, UK.
Nat Rev Dis Primers. 2018 Apr 12;4:18017. doi: 10.1038/nrdp.2018.17.
Autoimmune hepatitis (AIH) is a severe liver disease that affects children and adults worldwide. The diagnosis of AIH relies on increased serum transaminase and immunoglobulin G levels, presence of autoantibodies and interface hepatitis on liver histology. AIH arises in genetically predisposed individuals when a trigger, such as exposure to a virus, leads to a T cell-mediated autoimmune response directed against liver autoantigens; this immune response is permitted by inadequate regulatory immune control leading to a loss of tolerance. AIH responds favourably to immunosuppressive treatment, which should be started as soon as the diagnosis is made. Standard regimens include fairly high initial doses of corticosteroids (prednisone or prednisolone), which are tapered gradually as azathioprine is introduced. For those patients who do not respond to standard treatment, second-line drugs should be considered, including mycophenolate mofetil, calcineurin inhibitors, mechanistic target of rapamycin (mTOR) inhibitors and biologic agents, which should be administered only in specialized hepatology centres. Liver transplantation is a life-saving option for those who progress to end-stage liver disease, although AIH can recur or develop de novo after transplantation. In-depth investigation of immune pathways and analysis of changes to the intestinal microbiota should advance our knowledge of the pathogenesis of AIH and lead to novel, tailored and better tolerated therapies.
自身免疫性肝炎(AIH)是一种严重的肝脏疾病,影响全球的儿童和成人。AIH 的诊断依赖于血清转氨酶和免疫球蛋白 G 水平升高、存在自身抗体和肝组织学上的界面肝炎。当个体存在遗传易感性时,如暴露于病毒,触发因素会导致针对肝自身抗原的 T 细胞介导的自身免疫反应;这种免疫反应被允许是因为调节性免疫控制不足,导致耐受丧失。AIH 对免疫抑制治疗反应良好,一旦确诊应尽快开始治疗。标准方案包括相当高的初始剂量的皮质类固醇(泼尼松龙或泼尼松),随着巯嘌呤的引入逐渐减少剂量。对于那些对标准治疗无反应的患者,应考虑二线药物,包括霉酚酸酯、钙调神经磷酸酶抑制剂、雷帕霉素(mTOR)抑制剂和生物制剂,这些药物应仅在专门的肝脏病学中心使用。对于进展为终末期肝病的患者,肝移植是一种挽救生命的选择,尽管 AIH 可能在移植后复发或新发。对免疫途径的深入研究和对肠道微生物群的变化分析应能增进我们对 AIH 发病机制的认识,并导致新的、量身定制的、更耐受的治疗方法。
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