Fatigue in Cirrhosis

Abstract

Fatigue is a common symptom in patients with liver disease and has a significant impact on the health-related quality of life (HR-QoL). Its pathogenesis is poorly understood and is considered multifactorial. The liver is central in the pathogenesis of fatigue because it uniquely regulates much of the production, storage, and release of substrate for energy generation. Also, the liver "cross-talks" with the key organs that are responsible for this symptom complex-gut, skeletal muscle, and brain. Fatigue can have both peripheral (i.e., neuromuscular) and central (i.e., resulting from changes in neurotransmission within the brain) components. The treatment strategies for the management of fatigue are behavioral changes and pharmacotherapy, along with dietetic intervention and exercise. However, there is no consensus on management strategies for fatigue in patients with liver disease. This article gives an overview of fatigue as a concept, its pathophysiology, measures to evaluate fatigue in patients with liver disease, the impact of fatigue on chronic liver disease, assessment of fatigue in an appropriate clinical setting, and various interventions to manage fatigue.

Keywords: 6MWD, 6 min walk distance; ACG, anterior cingulate gyrus; ADL, activities of daily living; BBB, blood-brain barrier; BNST, bed nucleus of stria terminalis; CEC, cerebral endothelial cell; CFS, chronic fatigue syndrome; CPET, cardio-pulmonary exercise testing; CRH, corticotropin release hormone; DA, dopamine; FAS, fatigue assessment scale; FIS, fatigue impact scale; FSS, fatigue severity scale; HGS, hand-grip strength; HPA, hypothalamus-pituitary-adrenal; HR-QoL, health-related quality of life; IADL, instrumental activities of daily living; ME, meningo-encephalomyelitis; ME, meningoencephalitis; NAFLD, nonalcoholic fatty liver disease; NM, neuromuscular; NO, nitric oxide; PGE2, prostaglandins; PRO, patient-reported outcomes; PROMIS-F, patient-reported outcome measure information system for fatigue; PSC, primary sclerosing cholangitis; SAMe, S-adenosyl-methionine; SN, substantia nigra; SPPB, short-physical performance battery; VAS-F, visual analog scalefatigue; VTA, ventral tegmental area; central fatigue; chronic liver disease; health-related quality of life [HR-QoL]; iNOS, inducible nitric oxide synthase; patient-related outcomes [PRO]; peripheral fatigue; vmPFC, ventromedial prefrontal cortex.