Effects of Switching from Fenofibrate to Pemafibrate for Asymptomatic Primary Biliary Cholangitis.

Background/aims: The addition of a fibrate to ursodeoxycholic acid (UDCA) is the standard treatment for asymptomatic primary biliary cholangitis (aPBC) with an incomplete response to UDCA. Among the fibrates, bezafibrate and fenofibrate increase the serum creatinine level and reduce the estimated glomerular filtration rate (eGFR). Pemafibrate is an selective peroxisome proliferator-activated receptor alpha modulator (SPPARM-α) mainly metabolized by the liver that was recently approved to treat dyslipidemia.

Hydrophobic bile acids suppress expression of AE2 in biliary epithelial cells and induce bile duct inflammation in primary biliary cholangitis.

Understanding the mechanisms of chronic inflammation in primary biliary cholangitis (PBC) is essential for successful treatment. Earlier work has demonstrated that patients with PBC have reduced expression of the anion exchanger 2 (AE2) on biliary epithelial cells (BEC) and deletion of AE2 gene has led to a PBC-like disorder in mice. To directly address the role of AE2 in preventing PBC pathogenesis, we took advantage of our ability to isolate human BEC and autologous splenic mononuclear cells (SMC).

The developmental program of human dendritic cells is operated independently of conventional myeloid and lymphoid pathways.

Two distinct dendritic cell (DC) subsets, conventional DCs (cDCs) and plasmacytoid DCs (pDCs), have been shown to develop via either the myeloid or the lymphoid pathway in murine hematopoiesis. Lineage-specific phenotypes or functions of "myeloid" and "lymphoid" DCs, however, still remain elusive. Furthermore, such analysis has been particularly difficult in humans, due to lack of an assay system appropriate for the analysis of human stem and progenitor cell differentiation.