Alejandro Costaguta, Guillermo Costaguta, Fernando Álvarez
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Although steroids are the standard treatment for induction therapy, other medications may be considered. Cyclosporin A, a calcineurin inhibitor that decreases T cell activation, has proven effective for induction of remission, but its long-term side effects limit its appeal for maintenance. Tacrolimus, a drug belonging to the same family, has been used in patients with refractory diseases with fewer side effects. Sirolimus and everolimus have interesting effects on regulatory T cell populations and may become viable options in the future. Mycophenolate mofetil is not effective for induction but is a valid alternative for patients who are intolerant to azathioprine. B cell-depleting drugs, such as rituximab and belimumab, have been successfully used in refractory cases and are useful in both the short and long term. Other promising treatments include anti-tumor necrosis factors, Janus kinases inhibitors, and chimeric antigen receptor T cell therapy. 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引用次数: 0
摘要
自身免疫性肝炎是一种不常见的疾病,成人和儿童均可患病,其特点是肝脏长期反复出现炎症活动。这种炎症伴随着 IgG 和自身抗体水平的升高。传统的治疗方法是在使用类固醇的同时加用硫唑嘌呤,约有 80% 的患者病情得到缓解。尽管在过去二十年中,我们对免疫系统的认识有了长足的进步,但对治疗算法的修改却寥寥无几,这些算法自 40 多年前首次提出以来基本未变。本综述总结了目前可用的各种治疗方案以及我们使用这些方案的经验。尽管类固醇是诱导治疗的标准疗法,但也可以考虑使用其他药物。环孢素 A 是一种能降低 T 细胞活化的钙神经蛋白抑制剂,已被证明对诱导缓解有效,但其长期的副作用限制了它对维持治疗的吸引力。他克莫司(Tacrolimus)属于同类药物,用于难治性疾病患者,副作用较小。西罗莫司(Sirolimus)和依维莫司(everolimus)对调节性 T 细胞群有有趣的影响,未来可能成为可行的选择。霉酚酸酯(Mycophenolate mofetil)对诱导无效,但对硫唑嘌呤不耐受的患者来说是一种有效的替代疗法。利妥昔单抗(rituximab)和贝利木单抗(belimumab)等B细胞消耗药物已成功用于难治性病例,在短期和长期内均有疗效。其他有前景的治疗方法包括抗肿瘤坏死因子、Janus 激酶抑制剂和嵌合抗原受体 T 细胞疗法。随着治疗手段的不断丰富,我们可以想象在不久的将来,治疗自身免疫性肝炎的方法将更加量身定制。
Autoimmune hepatitis: Towards a personalized treatment.
Autoimmune hepatitis is an uncommon condition that affects both adults and children and is characterized by chronic and recurrent inflammatory activity in the liver. This inflammation is accompanied by elevated IgG and autoantibody levels. Historically, treatment consists of steroids with the addition of azathioprine, which results in remission in approximately 80% of patients. Despite significant advancements in our understanding of the immune system over the past two decades, few modifications have been made to treatment algorithms, which have remained largely unchanged since they were first proposed more than 40 years ago. This review summarized the various treatment options currently available as well as our experiences using them. Although steroids are the standard treatment for induction therapy, other medications may be considered. Cyclosporin A, a calcineurin inhibitor that decreases T cell activation, has proven effective for induction of remission, but its long-term side effects limit its appeal for maintenance. Tacrolimus, a drug belonging to the same family, has been used in patients with refractory diseases with fewer side effects. Sirolimus and everolimus have interesting effects on regulatory T cell populations and may become viable options in the future. Mycophenolate mofetil is not effective for induction but is a valid alternative for patients who are intolerant to azathioprine. B cell-depleting drugs, such as rituximab and belimumab, have been successfully used in refractory cases and are useful in both the short and long term. Other promising treatments include anti-tumor necrosis factors, Janus kinases inhibitors, and chimeric antigen receptor T cell therapy. This growing armamentarium allows us to imagine a more tailored approach to the treatment of autoimmune hepatitis in the near future.