Fundacion de Investigación Hospital Clinico Universitario de Valencia-INCLIVA, Valencia, Spain.
Servicio de Medicina Digestiva, Hospital Arnau de Vilanova de Valencia, Valencia, Spain.
J Transl Med. 2024 Jan 12;22(1):49. doi: 10.1186/s12967-023-04844-7.
Rifaximin is a non-reabsorbable antibiotic which acts at gut level, and improves cognition and inflammatory parameters in minimal hepatic encephalopathy (MHE) patients, but not all patients show the same level of response. This study aims to assess brain activity, both within and between brain networks, following rifaximin treatment, considering the differences between response groups as well.
Twenty-two healthy controls and 53 patients with cirrhosis (22 without and 31 with MHE, diagnosed by Psychometric Hepatic Encephalopathy Score, PHES) performed psychometric, attention and coordination tests, and blood inflammatory parameters were measured. Resting-state functional magnetic resonance imaging (fMRI) acquisitions were performed on controls and MHE patients. Eighteen MHE patients underwent a rifaximin treatment for 6 months, after which all measures were repeated. fMRI images were analysed and changes after treatment were assessed.
After rifaximin treatment, 13 patients improved their PHES score (Responder patients) while 5 did not (Non-responder patients). No significant decrease in blood ammonia was observed after rifaximin treatment, but there was a decrease in plasma inflammatory cytokines in responder patients. A global effect of rifaximin was detected on the sensorimotor and fronto-parietal networks. Responder patients showed a relative increase of thalamic network connectivity in comparison to non-responder patients. Before treatment, responder and non-responder patients showed connectivity differences in basal ganglia network. The connection of the sensorimotor and thalamic networks between them and with other networks suffered changes after treatment. These connections between networks mostly decreased after treatment. All changes and differences showed a significant level of correlation with the performance of psychometric tests and the blood levels of inflammatory biomarkers.
There was an improvement of the communication between executive, motor and attention-related brain areas, and their functional independence following rifaximin treatment. Patients who respond also show a less deteriorated connection involved in these functions before treatment. Results suggest that the improved inflammatory state of MHE patients, following rifaximin treatment would favour the observed changes in brain function and enhanced cognitive performance.
利福昔明是一种不可吸收的抗生素，作用于肠道水平，可改善轻微肝性脑病（MHE）患者的认知和炎症参数，但并非所有患者的反应水平都相同。本研究旨在评估利福昔明治疗后大脑活动，包括脑内和脑间网络，同时考虑反应组之间的差异。
22 名健康对照者和 53 名肝硬化患者（22 名无 MHE，31 名有 MHE，通过心理肝性脑病评分 PHES 诊断）进行心理测量、注意力和协调测试，测量血液炎症参数。对健康对照者和 MHE 患者进行静息态功能磁共振成像（fMRI）采集。18 名 MHE 患者接受利福昔明治疗 6 个月，治疗后重复所有测量。分析 fMRI 图像并评估治疗后的变化。
利福昔明治疗后，13 名患者 PHES 评分改善（应答者），5 名患者无改善（非应答者）。利福昔明治疗后血氨无明显下降，但应答者血浆炎症细胞因子下降。利福昔明治疗后检测到感觉运动和额顶叶网络的全局效应。与非应答者相比，应答者的丘脑网络连接相对增加。治疗前，应答者和非应答者的基底节网络存在连接差异。治疗后，它们之间以及与其他网络的感觉运动和丘脑网络连接发生变化。治疗后这些网络之间的连接大多减少。所有变化和差异与心理测试表现和炎症生物标志物的血液水平均有显著相关性。
利福昔明治疗后，执行、运动和注意力相关脑区之间的通讯得到改善，其功能独立性得到提高。应答者在治疗前也表现出与这些功能相关的连接恶化程度降低。结果表明，MHE 患者经利福昔明治疗后炎症状态改善，有利于观察到的大脑功能变化和认知能力提高。
