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In both models, treatment with 30mg/kg OCA reduced serum transaminases up to 30%, but did not improve fibrosis. The limited impact on fibrosis was due to cholestasis-independent worsening of ductular reaction by OCA in both disease models; OCA but not EDP-305 at therapeutic doses promoted ductular proliferation in healthy mice and favored differentiation of primary HPC towards cholangiocyte lineage in vitro. CONCLUSIONS EDP-305 potently improved pre-established liver injury and hepatic fibrosis in murine biliary and metabolic models of