Evolving therapeutic landscape of primary biliary cholangitis: A review.

Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease characterized by progressive bile duct destruction, leading to fibrosis, cirrhosis, and eventual liver failure. Over the past two decades, significant advancements have paved the way for novel therapeutic strategies. Ursodeoxycholic acid (UDCA) has been the cornerstone of PBC management, improving survival and delaying disease progression in most patients. However, up to 40% of patients demonstrate an inadequate response to UDCA, necessitating additional treatment options. Obeticholic acid (OCA), a farnesoid X receptor agonist, has emerged as a second-line therapy, showing efficacy in reducing alkaline phosphatase levels and improving liver biochemistry. Beyond UDCA and OCA, a new wave of therapeutic agents are reshaping the PBC landscape. These include fibrates, peroxisome proliferator-activated receptor agonists and novel immunomodulatory drugs aimed at reducing autoimmune-mediated liver injury. Bile acid transport inhibitors, anti-fibrotic agents, and gut microbiome-targeted therapies are also under investigation, offering hope for personalized treatment approaches. This review highlights the evolution of PBC therapy, emphasizing the unmet needs of patients with refractory disease and the potential of emerging therapies to improve outcomes. As the therapeutic landscape continues to expand, optimizing treatment strategies through precision medicine holds the promise of transforming the management of PBC.