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Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are two chronic cholestatic liver diseases affecting bile ducts that may progress to biliary cirrhosis. In the past few years, the increasing knowledge in the pathogenesis of both diseases led to a growing number of clinical trials and possible new targets for therapy. In this review, we provide an update on the treatments in clinical use and summarize the new drugs in trials for PBC and PSC patients. Farnesoid X Receptor (FXR) agonists and Pan-Peroxisome Proliferator-Activated Receptor (PPAR) agonists are the most promising agents and have shown promising results in both PBC and PSC. Fibroblast Growth Factor 19 (FGF19) analogues also showed good results, especially in PBC, while, although PBC and PSC are autoimmune diseases, immunosuppressive drugs had disappointing effects. Since the gut microbiome could have a potential role in the pathogenesis of PSC, recent research focused on molecules that could change the microbiome, with good results. The near future of the medical management of these diseases may include new treatments or a combination of multiple drugs targeting different signaling pathways at different stages of the diseases.
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http://dx.doi.org/10.3390/jcm10081763 | DOI Listing |
Biochem Biophys Res Commun
August 2025
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, No.163 Xianlin Avenue, Nanjing 210023, China. Electronic address:
Obeticholic acid (OCA) is a potent farnesoid X receptor (FXR) agonist used in the treatment of liver diseases associated with cholestasis, such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). However, its clinical utility is limited by dose-dependent hepatotoxicity, and the precise mechanism underlying OCA toxicity remains unclear. In this study, we investigated the mechanistic link between cholestasis-induced gut dysbiosis and OCA-associated hepatotoxicity.
View Article and Find Full Text PDFMedicine (Baltimore)
August 2025
The Eighth Clinical Medical College, Guangzhou University of Chinese Medicine, Foshan, Guangdong, China.
Autoimmune liver diseases (AILDs), including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC), often have complex interactions with thyroid diseases (TDs), such as hypothyroidism, hyperthyroidism, and Hashimoto thyroiditis (HT). These conditions frequently coexist and may share common autoimmune mechanisms, but their exact relationship remains poorly understood. Chronic hepatitis C (CHC), a viral liver disease, also affects thyroid function, but its interaction with TD is still under investigation.
View Article and Find Full Text PDFClin Mol Hepatol
September 2025
Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.
Background & Aims: Bezafibrate (BZF), a dual peroxisome proliferator-activated receptor/pregnane X receptor agonist, has demonstrated efficacy in combination with ursodeoxycholic acid (UDCA) for primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Although one of the therapeutic effects of BZF is suppression of bile acid synthesis, its specific impact on bile acid synthesis pathways has not been thoroughly explored. This study investigated bile acid profiles, synthesis intermediates, and their associations with liver biochemistries in patients with PBC and PSC, and evaluated the impact of BZF treatment on these associations.
View Article and Find Full Text PDFDiabetol Metab Syndr
August 2025
Department of General Surgery, University-Town Hospital of Chongqing Medical University, No. 55, University Town Middle Road, Shapingba District, Chongqing, 400000, China.
Background: Type 1 diabetes (T1D) and autoimmune liver diseases (AILDs), including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC), are characterized by immune-mediated damage. Prior observational studies have reported associations between these conditions, but definitive causal relationships remain elusive. This study leverages genetic data to clarify the nature of these associations.
View Article and Find Full Text PDFHepatol Commun
September 2025
Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
Background: Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are immune-mediated cholestatic disorders characterized by progressive biliary inflammation and fibrosis, for which treatment options remain limited, underscoring the need for novel therapeutic targets. The leukemia inhibitory factor (LIF) is an IL-6-related cytokine that dysregulates the communication between epithelial cells and extracellular matrices by binding a heterodimeric complex formed by LIF receptor (LIFR) and gp130. The role of the LIF/LIFR system in PSC and PBC and its potential as a therapeutic target remain unclear.
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