Hepatic encephalopathy: Sometimes more portal than hepatic

Abstract

Hepatic encephalopathy is a severe complication of both chronic and acute liver diseases. The term hepatic encephalopathy stems from the belief that hepatic insufficiency is its fundamental etiopathogenic factor. However, most clinical cases show liver failure along with mesenteric venous portal hypertension. This portal hypertension would explain the abnormal mechanical forces suffered by the digestive tract in the early stages of the disorder. These forces could regulate some gut biochemical pathological pathways in a process known as mechanotransduction. Thus, portal hypertension would begin with the establishment of a mechanotransduced afferent or sensory inflammatory gut‐brain pathway, resulting in functional and structural changes in the central nervous system. In this review, we will revisit the term “hepatic encephalopathy” in light of new results where portal hypertension occurs before liver failure and is accompanied by brain changes. Moreover, we will point out cellular links that can explain the microbiota, immune, gut, and brain axis disturbances found in this disorder.

Distinct prognostic value of different portal hypertension-associated features in patients with primary biliary cholangitis

“…We are aware that ascites and hepatic encephalopathy are not part of the initially proposed Baveno VI guidelines either. We nonetheless decided to include these parameters in our definition of CSPH since both have been associated with portal hypertension [46][47][48] and regularly occur during end-stage chronic liver disease.…”

Mast cell-mediated splanchnic cholestatic inflammation

“…The increase of portal pressure also spreads to the post-capillar venules of the splanchnic venous system and can produce gastrointestinal impairments by mechanotransduction [38]. In particular, the excessive mechanical energy acting over the gastrointestinal venous vascular wall would not only affect the endothelium through mechanotransduction, but also those cells that are in its neightborhood, like the gastrointestinal mast cells [39]. Thus, the increase of mast cells in cholestatic rats with portal hypertension could be related to the mechanotransductor stimulus caused by portal hypertension.…”

“…Likewise, due to the close relationship that the mast cells have with neurons, they would produce neurogenic inflammation and portal hypertensive encephalopathy [39]. The mediators released by the mast cells that bypass the liver and reach the systemic circulation through the portosystemic collateral vessels would also take part [17,26] in the development of this type of encephalopathy [39].…”

The Lymphatic Headmaster of the Mast Cell-Related Splanchnic Inflammation in Portal Hypertension

“…Particularly, the splanchnic post-capillary venule endothelium has great sensibility to the portal pressure increase, when the hypertension is secondary to a liver disease. This fact allows for an early change in the endothelium phenotype, which expresses an inflammatory phenotype before developing hepatic insufficiency [7].…”