Role of peripheral inflammation in minimal hepatic encephalopathy.
Por:
Llansola M, Izquierdo-Altarejos P, Montoliu C, Mincheva G, Palomares-Rodriguez A, Pedrosa MA, Arenas YM and Felipo V
Publicada:
23 ago 2024
Ahead of Print:
23 ago 2024
Resumen:
Many patients with liver cirrhosis show minimal hepatic encephalopathy (MHE) with mild cognitive impairment (MCI) and motor alterations that reduce their quality of life. Some patients with steatotic liver disease also suffer MCI. To design treatments to improve MHE/MCI it is necessary to understand the mechanisms by which liver disease induce them. This review summarizes studies showing that appearance of MHE/MCI is associated with a shift in the immunophenotype leading to an "autoimmune-like" form with increased pro-inflammatory monocytes, enhanced CD4 T and B lymphocytes activation and increased plasma levels of pro-inflammatory cytokines, including IL-17, IL-21, TNFa, IL-15 and CCL20. The contribution of peripheral inflammation to trigger MHE is supported by studies in animal models and by the fact that rifaximin treatment reverses MHE in around 60% of patients in parallel with reversal of the changes in peripheral inflammation. MHE does not improve in patients in which peripheral inflammation is not improved by rifaximin. The process by which peripheral inflammation induces MHE involves induction of neuroinflammation in brain, with activation of microglia and astrocytes and increased pro-inflammatory TNFa and IL-1ß, which is observed in patients who died with steatotic liver disease (SLD) or liver cirrhosis and in animal models of MHE. Neuroinflammation alters glutamatergic and GABAergic neurotransmission, leading to cognitive and motor impairment. Transmission of peripheral alterations into the brain is mediated by infiltration in brain of extracellular vesicles from plasma and of cells from the peripheral immune system. Acting on any step of the process peripheral inflammation - neuroinflammation - altered neurotransmission may improve MHE.
Filiaciones:
:
Laboratory of Neurobiology, Centro de Investigación Príncipe Felipe, Valencia, Spain
:
Laboratory of Neurobiology, Centro de Investigación Príncipe Felipe, Valencia, Spain
:
Departamento de Patología, Facultad de Medicina, Universidad Valencia, Valencia, Spain
Fundación de Investigación Hospital Clínico Universitario de Valencia-INCLIVA, Valencia, Spain
:
Laboratory of Neurobiology, Centro de Investigación Príncipe Felipe, Valencia, Spain
Palomares-Rodriguez A:
Laboratory of Neurobiology, Centro de Investigación Príncipe Felipe, Valencia, Spain
Pedrosa MA:
Laboratory of Neurobiology, Centro de Investigación Príncipe Felipe, Valencia, Spain
:
Laboratory of Neurobiology, Centro de Investigación Príncipe Felipe, Valencia, Spain
Departamento de Patología, Facultad de Medicina, Universidad Valencia, Valencia, Spain
:
Laboratory of Neurobiology, Centro de Investigación Príncipe Felipe, Valencia, Spain.
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