Primary biliary cholangitis.

Primary biliary cholangitis is a chronic, autoimmune, cholestatic disease that mainly affects women aged 40-70 years. Recent epidemiological studies have shown an increasing incidence worldwide despite geographical heterogeneity and a decrease in the female-to-male ratio of those the disease affects. Similar to other autoimmune diseases, primary biliary cholangitis occurs in genetically predisposed individuals upon exposure to environmental triggers, specifically xenobiotics, smoking, and the gut microbiome. Notably, the diversity of the intestinal microbiome is diminished in individuals with primary biliary cholangitis. The intricate interplay among immune cells, cytokines, chemokines, and biliary epithelial cells is postulated as the underlying pathogenic mechanism involved in the development and progression of primary biliary cholangitis, and extensive research has been dedicated to comprehending these complex interactions. Following the official approval of obeticholic acid as second-line treatment for patients with an incomplete response or intolerance to ursodeoxycholic acid, clinical trials have indicated that peroxisome proliferator activator receptor agonists are promising additional second-line drugs. Future dual or triple drug regimens might reach a new treatment goal of normalisation of alkaline phosphatase levels, rather than a decrease to less than 1·67 times the upper limit of normal levels, and potentially improve long-term outcomes. Improvement of health-related quality of life with better recognition and care of subjective symptoms, such as pruritus and fatigue, is also an important treatment goal. Promising clinical investigations are underway to alleviate these symptoms. Efforts to facilitate better access to medical care and dissemination of current knowledge should enable diagnosis at an earlier stage of primary biliary cholangitis and ensure access to treatments based on risk stratification for all patients.

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Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests ATan received support from the Health and Labor Sciences Research Grant (research on intractable hepatobiliary disease) issued by the Ministry of Health, Labor, and Welfare of Japan (grant number JPMH 23FC1026); consultant fees from EA Pharma, GlaxoSmithKline (GSK), and Kowa; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie and Gilead Sciences; received support for attending meetings and travel from GSK and Kowa; and participated on a data safety monitoring board or advisory board for GSK, EA Pharma, and Kowa. JMV received grants or contracts from CymaBay, Enanta, Escient, Genfit/Ipsen, Gilead, Intercept, NGM Pharmaceuticals, Novartis, Pliant, and Zydu; consulting fees from Arena, CymaBay, Intercept, Lilly, Moderna, and Novartis; is the Chairman of the Fractyl data and safety monitoring board; and is a member of the National Institute of Diabetes and Digestive and Kidney Diseases, the Drug Induced Liver Injury Network, and the Data and Safety Monitoring Board. XM and ATak declare no competing interests.