Changing face of hepatic encephalopathy: Role of inflammation and oxidative stress

Figure 1 The “Two-hit” hypothesis. In a background of liver injury and hyperammonemia, a second “hit”, such as an ammonia load following an upper gastrointestinal bleed, systemic inflammation/infection, or the development of hyponatremia can drive further astrocyte swelling, oxidative stress and lead to a rapid deterioration in neurocognitive function. The close relationship between astrocyte swelling and oxidative stress leads to an “auto-amplifying signalling loop”. The sites of action of potential therapies are indicated on the Figure. L-OL-A: L-ornithine L aspartate; NMDA: N-methyl D-aspartate; NSAID: Non-steroidal anti-inflammatory; TLR: Toll-like receptor.