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The researchers measured serum levels of ER\u03b1, oxidative stress indicators, and cytokines in PBC patients and healthy controls. They examined the expression of ER\u03b1, pyruvate dehydrogenase complex E2\u2010component (PDC\u2010E2), and apoptosis\u2010related proteins in the small bile ducts. In vitro experiments with HiBECs showed that estrogen had a dual effect on cell viability, increasing it at low concentrations but reducing it at higher concentrations. ER\u03b1 activation led to mitochondrial damage, apoptosis, and upregulation of ER\u03b1 and PDC\u2010E2 expression. These findings suggest that the high expression of ER\u03b1 in the bile ducts contributes to mitochondrial damage, inflammation, and apoptosis in PBC. 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