Advancing the management of primary biliary cholangitis: From pathogenesis to emerging therapies

Abstract

Primary biliary cholangitis is a chronic cholestatic autoimmune liver disease that progressively damages the bile ducts, leading to cholestasis and, in advanced stages, cirrhosis. While it primarily affects middle-aged women, recent data indicate a rising incidence in men. The interplay between genetic susceptibility, environmental exposures, and gut microbiome alterations is thought to drive disease onset. Diagnosis relies on persistent cholestatic enzyme elevation, disease-specific autoantibodies, and, in select cases, liver biopsy. Ursodeoxycholic acid remains the cornerstone of treatment, but many patients show an incomplete response. The recent withdrawal of obeticholic acid from the market, due to insufficient evidence of long-term benefit, has highlighted the urgent need for effective second-line therapies. Agonists of peroxisome proliferator- activated receptors, such as elafibranor and seladelpar, have demonstrated promising biochemical improvements and may reshape the therapeutic landscape. Future research is focused on refining risk assessment, optimizing treatment combinations, and addressing symptoms such as fatigue and pruritus to enhance patient well-being. A shift toward early intervention and personalized treatment strategies may further improve long-term outcomes in primary biliary cholangitis.

Keywords: Primary biliary cholangitis; Ursodeoxycholic acid; Peroxisome proliferator-activated receptors; Gut-liver axis; Cholestasis; Obeticholic acid; Fatigue; Pruritus

Core Tip: Primary biliary cholangitis (PBC) is a progressive autoimmune liver disease driven by a complex interplay of genetic, environmental, and microbial factors. Despite advances in early diagnosis and the widespread use of ursodeoxycholic acid, a significant subset of patients experiences incomplete biochemical response and disease progression. This review highlights recent breakthroughs in understanding PBC pathogenesis, the limitations of current therapies, including the withdrawal of obeticholic acid, and the emerging role of novel agents such as selective peroxisome proliferator-activated receptors agonists. Future strategies focusing on early intervention, personalized treatment, and symptom management may reshape the clinical management and prognosis of PBC.