Potential conflict of interest: Nothing to report.
Article first published online: 7 APR 2011
Copyright © 2011 American Association for the Study of Liver Diseases
Volume 53, Issue 4, pages 1372–1376, April 2011
How to Cite
Butterworth, R. F. (2011), Hepatic encephalopathy: A central neuroinflammatory disorder?. Hepatology, 53: 1372–1376. doi: 10.1002/hep.24228
Studies of the Neuroscience Research Unit are funded by the Canadian Institutes of Health Research.
- Issue published online: 7 APR 2011
- Article first published online: 7 APR 2011
- Accepted manuscript online: 11 FEB 2011 09:31AM EST
- Manuscript Accepted: 24 JAN 2011
- Manuscript Received: 17 NOV 2010
- Canadian Institutes of Health Research
Encephalopathy and brain edema are serious central nervous system complications of liver failure. Recent studies using molecular probes and antibodies to cell-specific marker proteins have demonstrated the activation of microglial cells in the brain during liver failure and confirmed a central neuroinflammatory response. In animal models of ischemic or toxic liver injury, microglial activation and concomitantly increased expression of genes coding for proinflammatory cytokines in the brain occur early in the progression of encephalopathy and brain edema. Moreover, the prevention of these complications with mild hypothermia or N-acetylcysteine (two treatments known to manifest both peripheral and central cytoprotective properties) averts central neuroinflammation due to liver failure. Recent studies using anti-inflammatory agents such as ibuprofen and indomethacin have shown promise for the treatment of mild encephalopathy in patients with cirrhosis, whereas treatment with minocycline, a potent inhibitor of microglial activation, attenuates the encephalopathy grade and prevents brain edema in experimental acute liver failure. The precise nature of the signaling mechanisms between the failing liver and central neuroinflammation has yet to be fully elucidated; mechanisms involving blood-brain cytokine transfer and receptor-mediated cytokine signal transduction as well as a role for liver-related toxic metabolites such as ammonia have been proposed. The prevention of central proinflammatory processes will undoubtedly herald a new chapter in the development of agents for the prevention and treatment of the central nervous system complications of liver failure. (HEPATOLOGY 2011;)