Ytting Henriette, Larsen Fin Stolze
Department of Hepatology A-2121, Rigshospitalet, University of Copenhagen , Copenhagen , Denmark.
Scand J Gastroenterol. 2015 Aug;50(8):1025-31. doi: 10.3109/00365521.2014.998271. Epub 2015 Apr 10.
Not all patients with autoimmune hepatitis (AIH) respond to standard medical therapy with corticosteroids and azathioprine. Such patients may develop end-stage liver disease with poor prognosis unless transplantation is considered. Alternatively, the introduction of new therapeutic strategies could potentially ameliorate deterioration of liver function. Patients in our tertiary center were selected for everolimus therapy when exhibiting nonresponse or intolerance to combinations of the standard and empirical drugs in use (e.g., mycophenolate mofetil, calcineurin inhibitors [CNIs]). We here report the efficacy of everolimus treatment of patients with AIH.
Seven patients (six female, mean age 47 years, range 22-62 years) in whom disease control could not be achieved with standard therapy or the alternative drugs in use were included.
Treatment with everolimus induced a clear reduction of transaminases within 2 weeks. After 3-5 months three patients had normal alanine aminotransferase (ALT) levels (10-45 IU) and four patients had ALT levels below 55 IU compared to a three- to fivefold elevated level prior to everolimus treatment. Sustained remission after 1 year of treatment was observed in three patients; in another two patients ALT was 45-68 U/L. Four patients in remission after 3 years were rebiopsied. Two showed no histological progression, and in two the fibrosis had decreased. Side effects noted were myalgias and minor bacterial infections not leading to discontinuation of the drug.
Our experience indicates that everolimus may be of value in selected patients with therapy-resistant AIH and comorbidity/side effects that excludes the use of CNIs.
并非所有自身免疫性肝炎（AIH）患者对皮质类固醇和硫唑嘌呤的标准药物治疗均有反应。此类患者可能会发展为预后不良的终末期肝病，除非考虑进行肝移植。另外，引入新的治疗策略可能会改善肝功能恶化的情况。在我们的三级医疗中心，当患者对标准药物和经验性药物（如霉酚酸酯、钙调神经磷酸酶抑制剂[CNIs]）联合使用无反应或不耐受时，会选择使用依维莫司进行治疗。我们在此报告依维莫司治疗AIH患者的疗效。
纳入7例患者（6例女性，平均年龄47岁，范围22 - 62岁），这些患者采用标准治疗或其他在用药物均无法实现疾病控制。
依维莫司治疗在2周内使转氨酶明显降低。3 - 5个月后，3例患者的丙氨酸氨基转移酶（ALT）水平正常（10 - 45 IU），4例患者的ALT水平低于55 IU，而在依维莫司治疗前ALT水平升高了三到五倍。3例患者在治疗1年后实现持续缓解；另外2例患者的ALT为45 - 68 U/L。4例在3年后缓解的患者接受了再次活检。2例无组织学进展，2例纤维化有所减轻。观察到的副作用为肌痛和轻度细菌感染，但未导致停药。
我们的经验表明，依维莫司对于某些对治疗耐药的AIH患者以及存在合并症/副作用而排除使用CNIs的患者可能具有价值。
