The pathogenesis of hepatic encephalopathy (HE) is complex and involves more than four major mechanisms, including the classical doctrine of ammonia toxicity, neurotransmitter alterations, inflammatory response, intestinal flora, premature failure of astrocytes, cerebral blood flow alterations, hemichannel dysfunction, and bile acids. 1. ammonia toxicity theory, liver dysfunction or the presence of portal shunt, blood ammonia concentration increases, diffusion into the brain of ammonia increases. 2. Neurotransmitter changes, including gamma-aminobutyric acid, glutamate, pseudoneurotransmitters, 5-hydroxytryptamine (5-HT) system, cholinergic system and other related changes. 3. Inflammatory response, hyperammonemia can act synergistically with inflammatory response to induce HE occurrence and development. 4. Intestinal flora, intestinal flora involved in the pathogenesis of HE mainly through the dysbiosis, increased ammonia production and mediated inflammatory response. 5. Premature astrocyte failure. Premature astrocyte failure is a downstream event of oxidative stress, which in turn affects neurotransmitter transmission and leads to the persistence of cognitive impairment in patients. 6. Altered cerebral blood flow, cerebral blood perfusion is critical for maintaining normal brain function, and patients with HE have dysfunctional cerebrovascular autoregulation, causing one of the key mediators of cerebral dysfunction. 7. Hemichannel dysfunction, neuronal energy deficit due to impaired hemichannel-mediated lactate transport between astrocytes and neurons may be one of the potential pathogenic mechanisms of HE. 8. Bile acids, when liver function is impaired, the level of circulating bile acids increases, which can damage the blood-brain barrier by impairing the tight junctions between vascular endothelial cells, leading to an increase in its permeability and contributing to the development of HE. These are the possible pathogenesis of hepatic encephalopathy (HE).