Diaz-Ruiz Raquel, Poca Maria, Roman Eva, Panadero-Gomez Rocio, Cuyàs Berta, Bañares Irene, Morales Angela, Puerto Marta, Lopez-Esteban Rocio, Blazquez Elena, Fernández-Castillo Marta, Correa-Rocha Rafael, Rapado-Castro Marta, Breton Irene, Bañares Rafael, Soriano German, Garcia-Martinez Rita
Department of Digestive Diseases, Instituto de Investigación Sanitaria, Hospital General Universitario Gregorio Marañón, Universidad Complutense Madrid, 28007 Madrid, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain.
Nutrients. 2025 Jan 9;17(2):226. doi: 10.3390/nu17020226.
Decompensated cirrhosis is characterized by systemic inflammation and innate and adaptive immune dysfunction. Hepatic encephalopathy (HE) is a prevalent and debilitating condition characterized by cognitive disturbances in which ammonia and inflammation play a synergistic pathogenic role. Extraskeletal functions of vitamin D include immunomodulation, and its deficiency has been implicated in immune dysfunction and different forms of cognitive impairment. The aim was to assess changes in cognitive function and inflammation in decompensated patients with cirrhosis receiving vitamin D supplementation. : Patients with cirrhosis discharged from decompensation in two tertiary hospitals in Spain (from September 2017 to January 2020) were assessed before, at 6 and 12 months after vitamin D supplementation. A comprehensive neuropsychological battery and neuroinflammatory markers were examined. In a subgroup of patients, peripheral immune blood cells were analyzed. : Thirty-nine patients were recruited. Of those, 27 completed the 6 months evaluation and were analyzed [age 62.4 ± 11.3 years; 22 men; Model for End-Stage Liver Disease (MELD) 11.7 ± 4.0; prior overt HE 33%; median 25-hydroxyvitamin D (25OHD) plasma level 12.7 µgr/L] and 22 achieved 12 months assessment. At baseline, learning and memory (R = 0.382; = 0.049) and working memory (R = 0.503; = 0.047) subtests correlated with plasma 25OHD levels. In addition, processing speed (R = -0.42; = 0.04), attention (R = -0.48; = 0.04), Tinnetti balance (R = -0.656; < 0.001) and Tinnetti score (R = -0.659; < 0.001) were linked to neuroinflammation marker IL-1β. Patients with lower 25OHD had a greater proportion of TH1cells at baseline and a larger amelioration of IL-1β and IL-6 following supplementation. An improvement in working memory was found after 25OHD replacement (46.7 ± 13 to 50 ± 11; = 0.047). : This study supports that vitamin D supplementation modulates low-grade inflammation in decompensated cirrhosis providing cognitive benefits, particularly in working memory.
失代偿期肝硬化的特征是全身炎症以及先天性和适应性免疫功能障碍。肝性脑病（HE）是一种常见且使人衰弱的病症，其特征为认知障碍，其中氨和炎症起协同致病作用。维生素D的骨骼外功能包括免疫调节，其缺乏与免疫功能障碍和不同形式的认知障碍有关。目的是评估补充维生素D的失代偿期肝硬化患者的认知功能和炎症变化。方法：对西班牙两家三级医院（2017年9月至2020年1月）中从失代偿期出院的肝硬化患者在补充维生素D之前、之后6个月和12个月进行评估。检查了一套全面的神经心理学测试和神经炎症标志物。在一组患者中，分析了外周免疫血细胞。结果：招募了39名患者。其中，27名完成了6个月的评估并进行了分析[年龄62.4±11.3岁；22名男性；终末期肝病模型（MELD）11.7±4.0；既往显性HE占33%；血浆25-羟维生素D（25OHD）水平中位数为12.7µg/L]，22名完成了12个月的评估。在基线时，学习和记忆（R = 0.382；P = 0.049）和工作记忆（R = 0.503；P = 0.047）子测试与血浆25OHD水平相关。此外，处理速度（R = -0.42；P = 0.04）、注意力（R = -0.48；P = 0.04）、Tinetti平衡（R = -0.656；P < 0.001）和Tinetti评分（R = -0.659；P < 0.001）与神经炎症标志物IL-1β相关。25OHD水平较低的患者在基线时TH1细胞比例较高，补充后IL-1β和IL-6的改善幅度较大。补充25OHD后工作记忆有改善（从46.7±13提高到50±11；P = 0.047）。结论：本研究支持补充维生素D可调节失代偿期肝硬化的低度炎症，带来认知益处，尤其是对工作记忆。
