摘要
Hepatic encephalopathy is a neurological complication result-ing from loss of hepatic function and is associated with poor clinical outcomes.During acute liver failure over 20%of mortality can be associated with the development of hepatic encephalopathy.In patients with liver cirrhosis,1-year sur-vival for those that develop overt hepatic encephalopathy is under 50%.The pathogenesis of hepatic encephalopathy is complicated due to the multiple disruptions in homeostasis that occur following a reduction in liver function.Of these,elevations of ammonia and neuroinflammation have been shown to play a significant contributing role to the develop-ment of hepatic encephalopathy.Disruption of the urea cycle following liver dysfunction leads to elevations of circulating ammonia,which enter the brain and disrupt the functioning of astrocytes.This results in dysregulation of metabolic path-ways in astrocytes,oxidative stress and cerebral edema.Besides ammonia,circulating chemokines and cytokines are increased following liver injury,leading to activation of micro-glia and a subsequent neuroinflammatory response.The combination of astrocyte dysfunction and microglia activation are significant contributing factors to the pathogenesis of hepatic encephalopathy.
基金
This study was funded by a VA Career Development award(BX003486)from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service to Dr.Matthew McMillin.This study was also funded by NIH R01 awards(DK082435 and DK112803)
a VA Merit award(BX002638)from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service to Dr.Sharon DeMorrow.This work was also supported by the resources of the Central Texas Veterans Health Care System Research Service,Temple,Texas.The content is t
作者简介
Corresponding author:Matthew McMillin,University of Texas at Austin Dell Medical School,1601 Trinity Street,Building B,Austin,TX 78701,USA.Tel:+1-512-495-5037,Fax:+1-512-495-5839,E-mail:matthew.mcmillin@austin.utexas.edu
