Clinical significance and pathogenic mechanisms of fatigue in metabolic dysfunction-associated steatotic liver disease

Fatigue is among the most common, albeit underestimated, symptoms in patients with metabolic dysfunction-associated steatotic liver disease. It affects quality of life and reduces the effectiveness of non-pharmacological interventions, thereby negatively affecting the prognosis. This review discusses the clinical problems associated with increased fatigue, explores diagnostic methods, considers key pathogenetic mechanisms of this symptom development (including neuroinflammation, hyperammonemia, mitochondrial and muscle dysfunction, sleep disorders, changes in the composition of gut microbiota), and describes the role of interorgan communication (the liver-brain and gut-brain axes) in the formation of the central link of fatigue. The presented data emphasize the need for an integrated approach to the diagnosis and correction of fatigue, which would include not only the impact on metabolic disorders, but also on neurophysiological and behavioral factors. Early assessment of fatigue and targeted interventions on key pathogenetic links can increase the effectiveness of non-pharmacological intervention (which currently form the basis of metabolic dysfunction-associated steatotic liver disease therapy) and improve the prognosis of patients with this chronic liver disease.