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利福昔明可选择性改善改善轻微肝性脑病患者免疫表型的变化。

Selective improvement by rifaximin of changes in the immunophenotype in patients who improve minimal hepatic encephalopathy.

机构信息

Fundación Investigación Hospital Clínico, Instituto de Investigación Sanitaria, INCLIVA, Avda Menéndez Pelayo, 4acc, 46010, Valencia, Spain.

Laboratory of Neurobiology, Centro Investigación Príncipe Felipe, Valencia, Spain.

出版信息

J Transl Med. 2019 Aug 28;17(1):293. doi: 10.1186/s12967-019-2046-5.

Abstract

BACKGROUND

Minimal hepatic encephalopathy (MHE) in cirrhotic patients is associated with specific changes in parameters of the immune system reflecting a more pro-inflammatory environment than in patients without MHE. The aims of this work were to assess the effects of rifaximin treatment of cirrhotic patients with MHE on: (1) MHE; (2) intermediate (CD14CD16) pro-inflammatory monocytes; (3) expression of early activation marker CD69 in T lymphocytes; (4) autoreactive CD4CD28 T lymphocytes; (5) differentiation of CD4 T lymphocytes to Th follicular and Th22; (6) serum IgG levels; and (7) levels of some pro-inflammatory cytokines.

METHODS

These parameters were measured by immunophenotyping and cytokine profile analysis in 30 controls without liver disease, 30 cirrhotic patients without MHE and 22 patients with MHE. Patients with MHE were treated with rifaximin and the same parameters were measured at 3 and 6 months of treatment. We assessed if changes in these parameters are different in patients who improve MHE (responders) and those who remain in MHE (non-responders).

RESULTS

Rifaximin improved MHE in 59% of patients with MHE. In these responder patients rifaximin normalized all alterations in the immune system measured while in non-responders it normalizes only IL-6, CCL20, and differentiation of T lymphocytes to Th22. Non-responder patients do not show increased expression of CD69 before treatment.

CONCLUSIONS

Rifaximin normalizes changes in the immune system in patients who improve MHE but not in non-responders. Some alterations before treatment are different in responders and non-responders. Understanding these differences may identify predictors of the response of MHE to rifaximin.

摘要

背景

肝硬化患者的轻微型肝性脑病(MHE)与免疫系统参数的特定变化相关,这些变化反映了比无 MHE 的患者更具炎症性的环境。本研究旨在评估利福昔明治疗 MHE 肝硬化患者对以下方面的影响:(1)MHE;(2)中间(CD14CD16)促炎单核细胞;(3)T 淋巴细胞早期激活标志物 CD69 的表达;(4)自身反应性 CD4CD28 T 淋巴细胞;(5)CD4 T 淋巴细胞向滤泡辅助性 Th 和 Th22 的分化;(6)血清 IgG 水平;(7)某些促炎细胞因子水平。

方法

通过免疫表型和细胞因子谱分析,在 30 名无肝病对照者、30 名无 MHE 肝硬化患者和 22 名 MHE 患者中测量了这些参数。MHE 患者接受利福昔明治疗,并在治疗 3 和 6 个月时测量了相同的参数。我们评估了这些参数在改善 MHE(应答者)和仍存在 MHE(无应答者)的患者中是否存在差异。

结果

利福昔明改善了 59%的 MHE 患者的 MHE。在这些应答者中,利福昔明使所有测量的免疫系统改变均恢复正常,而在无应答者中,仅使 IL-6、CCL20 和 T 淋巴细胞向 Th22 的分化恢复正常。无应答者在治疗前没有表现出 CD69 的高表达。

结论

利福昔明使改善 MHE 的患者的免疫系统改变恢复正常,但对无应答者无效。应答者和无应答者在治疗前的一些改变不同。了解这些差异可能有助于识别 MHE 对利福昔明反应的预测因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6db3/6714107/4a5e0f81c3f4/12967_2019_2046_Fig1_HTML.jpg

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