New PPAR therapies could slow fibrosis in primary biliary cholangitis
· Medical Xpressedited by Sadie Harley, reviewed by Andrew Zinin
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Primary biliary cholangitis is a rare autoimmune disease that affects the liver and can progress to cirrhosis. It occurs when the immune system attacks the small bile ducts within the liver. As a result, bile builds up, leading to inflammation and progressive liver damage. Although a first-line treatment exists, 40% of patients do not respond adequately to it or cannot tolerate it, so new treatment options need to be developed.
A study published in the journal Trends in Molecular Medicine reveals that peroxisome proliferator-activated receptors (PPARs) are emerging as a potential therapeutic target.
The study is led by Professor Manuel Vázquez-Carrera, from the UB's Faculty of Pharmacy and Food Sciences, the UB Institute of Biomedicine (IBUB) and the Sant Joan de Déu Research Institute (IRSJD), and head of the CIBER Area for Diabetes and Associated Metabolic Diseases (CIBERDEM).
From liver damage to cirrhosis
This new study presents the latest advances in understanding the role of PPARs in the development of the disease and shows how their activation influences processes associated with liver damage and the metabolic alterations characteristic of type 2 diabetes.
"The study analyzes the scientific evidence on PPAR agonists, a family of drugs that regulate processes essential for liver function. These include the recently approved drugs elafibranor and seladelpar, which have expanded treatment options for people with primary biliary cholangitis," says Professor Xavier Palomer, lead author of the article and a member of the research group led by Vázquez-Carrera.
According to the findings, activation of PPARs helps reduce inflammation, promotes a balance of bile acids—the accumulation of bile acids is toxic to the liver—and could slow the progression of fibrosis, one of the main factors associated with the deterioration of liver function.
Shared pathways with type 2 diabetes
Beyond their role in this disease, PPARs are involved in biological mechanisms shared with type 2 diabetes. Specifically, they regulate fat metabolism, insulin sensitivity and the inflammatory response—processes that are disrupted in both metabolic diseases and certain liver diseases.
Understanding these links may facilitate the development of treatments targeting common mechanisms and contribute to a more integrated understanding of both diseases.
According to the team, which has also analyzed the available clinical evidence on various PPAR agonists, these therapies have become one of the main options for patients requiring second-line treatment.
"However, further studies with longer follow-up periods are still needed to confirm their impact on disease progression and their long-term benefits," the researchers note.
Publication details
Xavier Palomer et al, The emerging role of PPARs in primary biliary cholangitis, Trends in Molecular Medicine (2026). DOI: 10.1016/j.molmed.2026.05.008
Journal information: Trends in Molecular Medicine
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Gastroenterology Provided by University of Barcelona Who's behind this story?
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