Mechanism-based target therapy in primary biliary cholangitis: opportunities before liver cirrhosis?

Frontiers in Immunology

Immunology

Yushu Yang¹  Lixia Gao²  XiaoSong He³  Patrick S. C. Leung³  Manuel Rojas⁴ 

[1] Department of Rheumatology and Immunology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China;Department of Rheumatology and Immunology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China;Division of Rheumatology, Allergy, and Clinical Immunology, University of California, Davis, Davis, CA, United States;Division of Rheumatology, Allergy, and Clinical Immunology, University of California, Davis, Davis, CA, United States;Division of Rheumatology, Allergy, and Clinical Immunology, University of California, Davis, Davis, CA, United States;Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogota, Colombia;

关键词: primary biliary cholangitis;    immune cells;    bile acids;    nuclear receptors;    liver fibrosis;   

DOI  :  10.3389/fimmu.2023.1184252

 received in 2023-03-11, accepted in 2023-05-16,  发布年份 2023

来源: Frontiers

【 摘 要 】

Primary biliary cholangitis (PBC) is an immune-mediated liver disease characterized by cholestasis, biliary injuries, liver fibrosis, and chronic non-suppurative cholangitis. The pathogenesis of PBC is multifactorial and involves immune dysregulation, abnormal bile metabolism, and progressive fibrosis, ultimately leading to cirrhosis and liver failure. Ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) are currently used as first- and second-line treatments, respectively. However, many patients do not respond adequately to UDCA, and the long-term effects of these drugs are limited. Recent research has advanced our understanding the mechanisms of pathogenesis in PBC and greatly facilitated development of novel drugs to target mechanistic checkpoints. Animal studies and clinical trials of pipeline drugs have yielded promising results in slowing disease progression. Targeting immune mediated pathogenesis and anti-inflammatory therapies are focused on the early stage, while anti-cholestatic and anti-fibrotic therapies are emphasized in the late stage of disease, which is characterized by fibrosis and cirrhosis development. Nonetheless, it is worth noting that currently, there exists a dearth of therapeutic options that can effectively impede the progression of the disease to its terminal stages. Hence, there is an urgent need for further research aimed at investigating the underlying pathophysiology mechanisms with potential therapeutic effects. This review highlights our current knowledge of the underlying immunological and cellular mechanisms of pathogenesis in PBC. Further, we also address current mechanism-based target therapies for PBC and potential therapeutic strategies to improve the efficacy of existing treatments.

【 授权许可】

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Copyright © 2023 Yang, He, Rojas, Leung and Gao