Experimental models of hepatic injury in Wilson disease: stage-specific mechanisms and translational applications

Background

Wilson disease (WD) is an autosomal recessive disorder of copper metabolism caused by pathogenic variants in ATP7B, with the liver being one of the earliest and most prominently affected organs. ATP7B dysfunction impairs copper incorporation into ceruloplasmin and biliary copper excretion, resulting in progressive hepatic copper accumulation and a cascade of pathological responses, including proteostasis disturbance, mitochondrial dysfunction, oxidative stress, metabolic remodeling, inflammation, and fibrogenesis. Given the dynamic progression of WD-associated liver injury from early copper dysregulation to chronic hepatitis, fibrosis, cirrhosis, and acute liver failure-like decompensation, appropriate experimental model selection is essential for mechanistic studies and therapeutic development.