INS and cholestasis: During preclinical studies OCA administration had significant beneficial effects in numerous disorders of enterohepatic system including improvement of estrogen-induced cholestasis, liver fibrosis, NASH, insulin signaling, portal hypertension, reduction of intestinal inflammation and improvement of ileal barrier function during cholestasis, improved bile acid-induced chronic diarrhea (Fiorucci et al., 2004, 2005; Adorini et al., 2012; Verbeke et al., 2014; Walters et al., 2015).