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Review
. 2006 Mar;20(3):181-8.
doi: 10.1155/2006/624832.

Fatigue in liver disease: pathophysiology and clinical management

Mark G Swain  1
Affiliations
Review

Fatigue in liver disease: pathophysiology and clinical management

Mark G Swain. Can J Gastroenterol. 2006 Mar.

Abstract
in English, French

Fatigue is the most commonly encountered symptom in patients with liver disease, and it has a significant impact on their quality of life. However, although some progress has been made with regard to the understanding of the processes which may generate fatigue in general, the underlying cause(s) of liver disease-associated fatigue remain incompletely understood. The present review describes recent advances which have been made in our ability to measure fatigue in patients with liver disease in the clinical setting, as well as in our understanding of potential pathways which are likely important in the pathogenesis of fatigue associated with liver disease. Specifically, experimental findings suggest that fatigue associated with liver disease likely occurs as a result of changes in neurotransmission within the brain. In conclusion, a reasonable approach to help guide in the management of the fatigued patient with liver disease is presented.

La fatigue est le principal symptôme chez les patients atteints d’une maladie hépatique, et elle a des conséquences considérables sur leur qualité de vie. Cependant, même si certains progrès ont été réalisés quant à notre compréhension des processus généraux susceptibles de produire de la fatigue, les causes sousjacentes de la fatigue associée à la maladie hépatique sont mal comprises. La présente analyse décrit les progrès récents accomplis dans notre capacité de mesurer la fatigue chez les patients atteints d’une maladie hépatique en milieu clinique, ainsi que dans notre compréhension des voies potentielles qui, selon toute probabilité, jouent un rôle important dans la pathogenèse de la fatigue associée à la maladie hépatique. Plus précisément, les observations expérimentales laissent supposer que la fatigue associée aux maladies hépatiques découle de modifications à la neurotransmission dans le cerveau. En conclusion, une démarche raisonnable pour orienter la prise en charge du patient atteint d’une maladie hépatique et de fatigue est présentée.

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Figures

Figure 1
Figure 1
Corticotropin-releasing hormone (CRH) acts in its traditional role to stimulate adrenocorticotropic hormone (ACTH) release from the anterior pituitary gland. However, CRH release from nerve fibres projecting to areas within the brain stimulates behavioural activation and arousal
Figure 2
Figure 2
Serotonin-secreting nerves originate in the dorsal raphe nucleus within the midbrain and their axons project throughout the central nervous system. Activation of 5-hydroxytryptamine 1A (5HT1A) autoreceptors located on serotonin nerve cell bodies within the raphe nucleus results in a decrease in serotonin release from nerve terminals at the distal projection sites of these serotonergic nerves. ↓ Decrease
Figure 3
Figure 3
Neural transmission pathway for liver to brain signalling. Kupffer cells within the liver secrete proinflammatory mediators (eg, cytokines, prostaglandins) that activate vagal afferent nerves, which innervate the liver. Nerve impulses are then carried to the nucleus tractus solitarius (NTS) within the brainstem, which acts as a relay centre for the transmission of these impulses to areas throughout the brain. Stimulation of vagal afferent nerves can thereby result in alterations in neurotransmitter systems within the brain, which may give rise to central fatigue
Figure 4
Figure 4
Humoral transmission pathway for liver to brain signalling. Substances released within the circulation in the setting of liver disease (eg, cytokines, including tumour necrosis factor-alpha [TNFα]) activate the cerebral endothelial cells that make up the blood-brain barrier. Activated cerebral endothelial cells then secrete secondary messengers (eg, nitric oxide, prostaglandin E2) into the brain parenchyma, which induce changes in central neurotransmitter systems, which give rise to central fatigue
See this image and copyright information in PMC

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