Another mechanism of the cholesterol-lowering effect of bezafibrate may be due to the stimulation of cholesterol efflux from hepatocytes to the bile canaliculi Napabucasin clinical trial by way of the activation of PPARs. Our experiment using HepaRG cells showed significantly up-regulated expression of ABCG5 and ABCG8 mRNA after bezafibrate but not rifampicin treatment (Fig. 5B). A similar effect of bezafibrate on ABCG5 in human liver has been reported previously.51 Because of the inhibition of bile acid synthesis and presumably the stimulation of cholesterol excretion into bile, bezafibrate significantly increases biliary cholesterol saturation.52 Indeed, increased risk of gallstone formation has been reported in

hyperlipidemic patients treated with another fibrate, fenofibrate.53 However, combination therapy of UDCA and bezafibrate appears to attenuate

the adverse effect of bezafibrate, because UDCA markedly lowers biliary cholesterol saturation and dissolves cholesterol gallstones.2 On the other hand, bezafibrate may augment the anticholestatic and antilithogenic actions of UDCA by inhibiting bile acid synthesis and increasing the proportion of UDCA (Fig. 2C). In addition to anticholestatic effects, activation of PXR54 and the PPARs55 has been reported to suppress inflammation through the inhibition of proinflammatory genes, including nuclear factor-κB (NF-κB), tumor necrosis factor-α, and interleukin-1α. In this study, although we did not evaluate the contribution of the antiinflammatory effects of bezafibrate to the selleck kinase inhibitor improvement of biochemical markers, bezafibrate is suggested to be an ideal drug with anticholestatic, hypolipidemic,

and even antiinflammatory actions on PBC by way of the activation of both PXR and PPARs. In summary, bezafibrate exhibited anticholestatic efficacy on PBC patients who showed an incomplete response to UDCA monotherapy. Although UDCA replaces hydrophobic bile acids and activates canalicular BSEP and MDR3 and basolateral MRP4,7 MCE bezafibrate inhibits hepatic synthesis and uptake of bile acids, enhances bile acid detoxification, and stimulates canalicular MDR3, MDR1 and MRP2 activities as a dual PPARs/PXR agonist (Fig. 6). These data lend support to the idea that combination therapy with UDCA and bezafibrate is an excellent method for the treatment of early-stage PBC patients who exhibit an incomplete biochemical response to UDCA monotherapy. Additional Supporting Information may be found in the online version of this article. “
“The aim of this systematic review was to evaluate the efficacy and safety of biological agents (vedolizumab, abatacept, visilizumab, golimumab) in patients with active moderate to severe ulcerative colitis. This paper was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines.