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The Scientific Basis of Cholestatic Liver Disease and Its Symptom Complex
Henry H Nguyen1, Mark G Swain2
1Division of Gastroenterology and Hepatology, Department of Medicine, Calgary Liver Unit, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive Northwest, Calgary, Alberta T2N 4N1, Canada; Division of Gastroenterology and Hepatology, Department of MIID, Calgary Liver Unit, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Abstract:
Cholestatic liver disease disrupts bile acid homeostasis and triggers systemic metabolic, immune, and neuroimmune changes that underpin complex symptom biology. Cholestasis-associated pruritus arises from proposed interacting peripheral mechanisms (eg, bile acids, autotaxin-lysophosphatidic acid, interleukin-31, endogenous opioids) and central itch processing within defined brain networks. Fatigue similarly reflects a convergence of peripheral immune and autonomic disturbances with central alterations in thalamic and basal ganglia connectivity, motor network control, and cognition, rather than simple muscle dysfunction.
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