New Therapeutic Targets in Autoimmune Cholangiopathies

Frontiers in Medicine

article

Alessio Gerussi¹  Pietro Invernizzi¹  Martina Luc๠ Laura Cristoferi¹  Vincenzo Ronca¹  Clara Mancuso¹  Chiara Milani¹  Daphne D'Amato¹  Sarah Elizabeth O'Donnell¹  Marco Carbone¹ 

[1] Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca;San Gerardo Hospital;National Institute of Health Research Liver Biomedical Research Centre Birmingham, Centre for Liver Research, Institute of Immunology and Immunotherapy, University of Birmingham, United Kingdom

关键词: primary biliary cholangitis;    primary sclerosing cholangitis;    liver;    FXR agonists;    fibrates;    microbiome;    gut-liver axis;   

DOI  :  10.3389/fmed.2020.00117

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are autoimmune cholangiopathies characterized by limited treatment options. A more accurate understanding of the several pathways involved in these diseases has fostered the development of novel and promising targeted drugs. For PBC, the characterization of the role of farnesoid X receptor (FXR) and perixosome-proliferator activated receptor (PPAR) has paved the way to several clinical trials including different molecules with choleretic and antinflammatory action. Conversely, different pathogenetic models have been proposed in PSC such as the “leaky gut” hypothesis, a dysbiotic microbiota or a defect in mechanisms protecting against bile acid toxicity. Along these theories, new treatment approaches have been developed, ranging from drugs interfering with trafficking of lymphocytes from the gut to the liver, fecal microbiota transplantation or new biliary acids with possible immunomodulatory potential. Finally, for both diseases, antifibrotic agents are under investigation. In this review, we will illustrate current understanding of molecular mechanisms in PBC and PSC, focusing on actionable biological pathways for which novel treatments are being developed.

【 授权许可】

CC BY