The liver-brain axis in liver failure: neuroinflammation and encephalopathy

Nat Rev Gastroenterol Hepatol. 2013 Sep;10(9):522-8. doi: 10.1038/nrgastro.2013.99. Epub 2013 Jul 2.


Systemic inflammation is common in liver failure and its acquisition is a predictor of hepatic encephalopathy severity. New studies provide convincing evidence for a role of neuroinflammation (inflammation of the brain per se) in liver failure; this evidence includes activation of microglia, together with increased synthesis in situ of the proinflammatory cytokines TNF, IL-1β and IL-6. Liver-brain signalling mechanisms in liver failure include: direct effects of systemic proinflammatory molecules, recruitment of monocytes after microglial activation, brain accumulation of ammonia, lactate and manganese, and altered permeability of the blood-brain barrier. Ammonia and cytokines might act synergistically. Existing strategies to reduce ammonia levels (including lactulose, rifaximin and probiotics) have the potential to dampen systemic inflammation, as does albumin dialysis, mild hypothermia and N-acetylcysteine, the latter two agents acting at both peripheral and central sites. Minocycline, an agent with potent central anti-inflammatory properties, reduces neuroinflammation, brain oedema and encephalopathy in liver failure, as does the anti-TNF agent etanercept.

Publication types

  • Review

MeSH terms

  • Cytokines / metabolism*
  • Etanercept
  • Hepatic Encephalopathy* / drug therapy
  • Hepatic Encephalopathy* / etiology
  • Hepatic Encephalopathy* / metabolism
  • Humans
  • Immunoglobulin G / therapeutic use*
  • Immunosuppressive Agents / therapeutic use
  • Inflammation / metabolism
  • Liver Failure / complications
  • Liver Failure / drug therapy
  • Liver Failure / metabolism
  • Receptors, Tumor Necrosis Factor / therapeutic use*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors


  • Cytokines
  • Immunoglobulin G
  • Immunosuppressive Agents
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Etanercept