吗替麦考酚酯治疗难治性自身免疫性肝炎患者疗效初步研究*

doi:10.3969/j.issn.1672-5069.2024.04.012

摘要/Abstract

摘要： 目的研究吗替麦考酚酯(MMF)治疗难治性自身免疫性肝炎(AIH)患者的临床效果。方法 2015年1月～2021年6月我院收治的的23例难治性AIH患者,均接受MMF联合甲泼尼龙片治疗20个月,依据病情逐步减量维持,完成随访至2年。治疗前后行肝穿刺活检。应用单因素和多因素Logistic回归分析影响挽救治疗应答的因素。结果治疗后,23例AIH患者血清ALT、AST和IgG水平分别为(63.7±13.4)U/L、(54.1±14.5)U/L和(13.8±3.5)g/L,均较治疗前显著下降【分别为(167.3±43.1)U/L、(124.8±22.6)U/L和(17.4±4.4)g/L,P<0.05】;治疗后肝组织纤维化评分为(2.0±1.1),炎症活动度评分为(1.5±1.3),均显著低于治疗前【分别为(2.7±1.6)和(2.4±1.2),P<0.05】;在随访结束时,临床缓解18例和应答不完全5例;入组时,临床缓解组女性占比显著低于应答不完全组(P<0.05),血清ALT、IgG、肝组织纤维化和炎症活动度评分显著低于治疗应答不完全组(P<0.05);多因素Logistic回归分析显示,女性(OR=1.04,95%CI=0.9～1.5)、治疗前IgG水平(OR =1.17,95%CI=1.0～2.3)和肝组织纤维化评分(OR =4.4,95%CI=1.8～9.3)为治疗应答的独立影响因素。结论对于难治性AIH患者,应用MMF补救治疗安全、有效,值得临床进一步扩大观察。

关键词: 自身免疫性肝炎, 难治, 吗替麦考酚酯, 泼尼松, 挽救治疗

Abstract: Objective This study aims to assess therapeutic efficacy and safety of mycophenolate mofetil (MMF) in rescue treatment of patients with refractory autoimmune hepatitis (rAIH). Methods 23 patients with rAIH were encountered in our hospital between January 2015 and June 2021, all were treated with MMF and methylprednisolone combination, doses were gradually tapped according to the improvement, and the regimen lasted for up to 20 months and followed-up for two years. Liver biopsies were carried out before and after treatment. Univariate and multivariate Logistic regression analysis were applied to predict impacting factors of response. Results By end of treatment, serum ALT, AST and IgG levels in 23 patients with rAIH were (63.7±13.4)U/L,(54.1±14.5)U/L and (13.8±3.5)g/L, all significantly decreased as compared to [(167.3±43.1)U/L, (124.8±22.6)U/L and (17.4±4.4)g/L, respectively, P<0.05] at presentation; liver tissue fibrosis score was (2.0±1.1) and hepatic activity index (HAI) was (1.5±1.3), both much lower than [(2.7±1.6) and (2.4±1.2), P<0.05] before treatment; by end of follow-up, complete clinical remission (CCR) was obtained in 18 cases and incomplete response (IR) in 5 cases; at enrollment, female proportion, serum ALT and IgG levels, liver fibrosis and HAI scores in patients with CCR were significantly lower than in those with IR (P<0.05); multivariate Logistic regression analysis showed that female (OR=1.04, 95%CI=0.9-1.5), serum IgG level (OR =1.17, 95%CI=1.0-2.3) and hepatic fibrosis score (OR =4.4, 95%CI=1.8-9.3) were all the independent factors impacting response to rescue therapy. Conclusion Rescue therapy with MMF is safe, reliable and efficacious in the treatment of patients with rAIH, which is worth further clinical trial to verify.

Key words: Autoimmune hepatitis, Refractory, Mycophenolate mofetil, Prednisolone, Rescue therapy

蒋瑶, 仲伟明, 周俏怡, 邵宁, 吕冰, 孙舒. 吗替麦考酚酯治疗难治性自身免疫性肝炎患者疗效初步研究^*[J]. 实用肝脏病杂志, 2024, 27(4): 539-542.

Jiang Yao, Zhong Weiming, Zhou Qiaoyi, et al. Rescued therapy of patients with refractory autoimmune hepatitis with mycophenolate mofetil[J]. Journal of Practical Hepatology, 2024, 27(4): 539-542.

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吗替麦考酚酯治疗难治性自身免疫性肝炎患者疗效初步研究^*

Rescued therapy of patients with refractory autoimmune hepatitis with mycophenolate mofetil

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