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however, evidence suggests that susceptibility to the disease results from the interplay between environmental triggers and genetic predisposition ( Figure 2 ), leading to dysregulation of bile acids synthesis and/or metabolism of and finally disruption of the biliary bicarbonate (HCO 3 - ) umbrella, which is critical for protecting the bile ducts from harmful bile acids through the secretion of HCO 3 - into the ductular lumen

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