Role of Peripheral Inflammation in Hepatic Encephalopathy

Abstract

A growing body of evidence now highlights a key role for systemic inflammation in altering behavior and mood in patients with liver disease. How inflammation occurring in the periphery in the context of liver disease, communicates with the brain to mediate changes in neurotransmission and thereby behavior is incompletely understood. Traditional routes of communication between the periphery and the brain involve neural (i.e. vagal afferent nerves) and humoral (blood-borne) pathways, with increased circulating levels of endotoxin and cytokines (especially Tumor Necrosis Factor a, TNFa) that occur during systemic inflammatory responses, as being primarily implicated in mediating signaling via these pathways. However, in recent years communication via peripheral immune-cell-to-brain and the gut-microbiota-to-brain routes have received increasing attention in the context of liver disease for their ability to modulate brain function, and generate a spectrum of symptoms ranging from fatigue and altered mood to overt Hepatic Encephalopathy (HE). In this review, we discuss periphery-to-brain communication pathways and their potential role in mediating systemic inflammationassociated alterations in behavior, that are in turn ultimately part of a spectrum of brain changes linked to the development of clinically apparent HE.

The Role of Intestinal Bacteria and Gut–Brain Axis in Hepatic Encephalopathy

“…Lipopolysaccharides administration transiently elevates blood levels of interleukin6 (IL6) and tumor necrosis factor-alpha (TNFa) ( Labrenz et al, 2019 ). Pro-inflammatory factors combine with the receptors expressed in Cerebral Endothelial Cells (CECs) to produce a secondary messenger, which induces oxidative stress and neuroinflammation ( Azhari and Swain, 2018 ). Compared to mice with healthy microbiota, there is a significant expression of inflammatory factors in the cortex of GF mice.…”

Longitudinal neurometabolic changes in the hippocampus of a rat model of chronic hepatic encephalopathy

“…[17][18][19] The mechanisms of NH 4 + neurotoxicity also implicate oxidative/nitrosative stress, mitochondrial dysfunction, cell-signalling disruption, neuroinflammation and alterations in neuronal process growth. 9,10,16,[20][21][22][23][24] While all these mechanisms appear implicated in the pathogenesis of HE, the sequence of events remains unclear, owing largely to the lack of reliable longitudinal studies.…”

Role of Tumor Necrosis Factor alpha promoter polymorphisms in interferon related side effects in chronic hepatitis B patients under interferon alpha 2b treatment

“…Nevertheless, when TNFα is present in peripheral circulation, it always induces inflammatory phenotype. Despite inflammation is key to overcome infections, number of studies proved the role of TNFα in variety of conditions including autoimmunity [11,12]. Impact of interferon administration in addition to antiviral treatment attracted many scientists all around the world due to unmet needs in CHB treatment [13,14].…”