Role of manganese in the pathophysiology of hepatic encephalopathy: scoping review protocol

Introduction: Hepatic encephalopathy (HE) is a neuropsychiatric complication of liver disease and/or portosystemic blood shunting, characterized by alterations of alertness, personality, cognition, and motor functions. Its severity is defined from mild symptoms to coma according to four grades. This disease may affect several brain regions including the cingulate gyrus, the insular cortex, and the globus pallidus. The pathophysiology of HE is thought to be multifactorial and involves manganese accumulation in the brain, damaging effect of ammonia on glial cells, etc. Previous studies describe the pathophysiology of HE or the effect of manganese in the central nervous system but there is no review addressing both topics from an integrative perspective and using a systematic methodology. This scoping review aims to evaluate the role of manganese in HE. Methods: Published studies (all publication types) will be retrieved from Web of Science, MEDLINE, Scopus, EBSCOhost, Ovid, and Google Scholar. Inclusion criteria are: studies reporting manganese levels in any biological sample or tissue of patients with HE, any experimental model reporting the effect of manganese administration on measures of neuroprotection in models of liver damage, or showing an effect on manganese levels in the liver and/or the brain. Exclusion criteria are: studies reporting subjects exposed occupationally or environmentally to manganese, or written in languages different than Spanish or English that could not be appropriately translated, or whose full-text files could not be retrieved. Either clinical or preclinical studies will be analyzed separately but might be discussed together. Data summaries will be presented in graphs, figures, and tables. A narrative synthesis will be presented. This protocol complies with PRISMA-P.