Burak Kelly W, Swain Mark G, Santodomingo-Garzon Tania, Lee Samuel S, Urbanski Stefan J, Aspinall Alexander I, Coffin Carla S, Myers Robert P
Liver Unit, Division of Gastroenterologyand Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
Can J Gastroenterol. 2013;27(5):273-80. doi: 10.1155/2013/512624.
Although most patients with autoimmune hepatitis (AIH) respond to treatment with prednisone and⁄or azathioprine, some patients are intolerant or refractory to standard therapy. Rituximab is an anti-CD20 monoclonal antibody that depletes B cells and has demonstrated efficacy in other autoimmune conditions.
To evaluate the safety and efficacy of rituximab in patients with refractory AIH in an open-label, single-centre pilot study.
Six patients with definite, biopsy-proven AIH who failed prednisone and azathioprine treatment received two infusions of rituximab 1000 mg two weeks apart and were followed for 72 weeks.
Rituximab was well tolerated with no serious adverse events. By week 24, mean (± SD) aspartate aminotransferase (AST) levels had significantly improved (90.0±23.3 U⁄L versus 31.3±4.2 U⁄L; P=0.03) and mean immunoglobulin G levels had fallen (16.4±2.0 g⁄L versus 11.5±1.1 g⁄L; P=0.056). The prednisone dose was weaned in three of four subjects, with one subject flaring after steroid withdrawal. Inflammation grade improved in all four subjects who underwent repeat liver biopsy at week 48. Regulatory T cell levels examined by FoxP3 immunohistochemistry paralleled inflammatory activity and did not increase on follow-up biopsies. There was no significant change in serum chemokine or cytokine levels from baseline to week 24 (n=5), although interferon-gamma-induced protein 10 levels improved in three of five subjects.
Rituximab was safe, well tolerated and resulted in biochemical improvement in subjects with refractory AIH. These results support further investigation of rituximab as a treatment for AIH.
虽然大多数自身免疫性肝炎（AIH）患者对泼尼松和/或硫唑嘌呤治疗有反应，但一些患者对标准治疗不耐受或难治。利妥昔单抗是一种抗CD20单克隆抗体，可消耗B细胞，并已在其他自身免疫性疾病中显示出疗效。
在一项开放标签、单中心的试点研究中评估利妥昔单抗对难治性AIH患者的安全性和疗效。
6例经活检证实为明确AIH且泼尼松和硫唑嘌呤治疗失败的患者，接受间隔两周的两次1000mg利妥昔单抗输注，并随访72周。
利妥昔单抗耐受性良好，无严重不良事件。到第24周时，平均（±标准差）天冬氨酸转氨酶（AST）水平显著改善（90.0±23.3U/L对31.3±4.2U/L；P=0.03），平均免疫球蛋白G水平下降（16.4±2.0g/L对11.5±1.1g/L；P=0.056）。4名受试者中有3名的泼尼松剂量逐渐减少，1名受试者在停用类固醇后病情复发。在第48周接受重复肝活检的所有4名受试者中，炎症分级均有所改善。通过FoxP3免疫组织化学检测的调节性T细胞水平与炎症活动平行，随访活检时未增加。从基线到第24周（n=5），血清趋化因子或细胞因子水平无显著变化，尽管5名受试者中有3名的γ干扰素诱导蛋白10水平有所改善。
利妥昔单抗安全、耐受性良好，并使难治性AIH患者的生化指标得到改善。这些结果支持进一步研究利妥昔单抗作为AIH的一种治疗方法。
