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Hippocampal neuroinflammation could contribute to cognitive decline in patients with liver disease, but this has yet to be studied. The study aims were to assess if hippocampus from patients who died with steatohepatitis or cirrhosis showed: (i) glial activation, (ii) altered cytokine content, (iii) immune cell infiltration, (iv) neuronal apoptosis and (v) neuronal loss.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Post\u2010mortem hippocampus was obtained from 6 controls, 19 patients with steatohepatitis (SH) and 4 patients with liver cirrhosis. SH patients were divided into SH1 (<jats:italic>n<\/jats:italic>\u2009=\u20099), SH2 (<jats:italic>n<\/jats:italic>\u2009=\u20096) and SH3 (<jats:italic>n<\/jats:italic>\u2009=\u20094) groups depending on disease severity. Glial activation, IL\u20101\u03b2 and TNF\u03b1 content, CD4 lymphocyte and monocyte infiltration, neuronal apoptosis and neuronal loss were analyzed by immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients who died in SH1 showed astrocyte activation, whereas those who died in SH2 also showed microglial activation, CD4 lymphocyte and monocyte infiltration, neuronal apoptosis and neuronal loss. These changes remained in patients in SH3, who also showed increased IL\u20101\u03b2 and TNF\u03b1. Patients who died of liver cirrhosis did not show CD4 lymphocyte infiltration, neuronal apoptosis or increase in TNF\u03b1, but still showed glial activation, increased IL\u20101\u03b2 and neuronal loss.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Patients with steatohepatitis showed glial activation, immune cell infiltration, apoptosis and neuronal loss. Glial activation and neuronal loss remained in cirrhotic patients. This may explain the irreversibility of some cognitive alterations in hepatic encephalopathy. Cognitive reserve may contribute to different grades of cognitive impairment despite similar neuronal loss.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.15935","type":"journal-article","created":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T08:21:42Z","timestamp":1687335702000},"page":"3032-3046","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Patients who died with steatohepatitis or liver cirrhosis show neuroinflammation and neuronal loss in hippocampus"],"prefix":"10.1111","volume":"30","author":[{"given":"Paola","family":"Leone","sequence":"first","affiliation":[{"name":"Laboratory of Neurobiology Centro de Investigaci\u00f3n Pr\u00edncipe Felipe  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaiza M.","family":"Arenas","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology Centro de Investigaci\u00f3n Pr\u00edncipe Felipe  Valencia 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