Evolving Goals Reshape the Treatment of Primary Biliary Cholangitis

While the management of primary biliary cholangitis (PBC) has been redefined by therapies that can achieve meaningful improvements in biomarkers of disease progression, personalized care and aspirational goals may take the management of this chronic liver disease to a whole new level. At The Liver Meeting 2025 in Washington, D.C., experts discussed a shift in the paradigm of PBC management marked not only by the evolution of pharmacologic therapies but also by new, patient-centered approaches to treatment.  

PBC is a chronic autoimmune liver disease with a global prevalence of approximately 18 cases per 100,000 people, which tends to affect women disproportionately. While PBC has a complex etiology involving both genetic predisposition and environmental factors, such as smoking and exposure to certain medications, it can also present with complex clinical manifestations that may pose therapeutic challenges. 

“The pillars of care in PBC are treatment of the underlying disease process and [improvement of] quality of life,” said Michele Tana, MD, associate professor of medicine at the University of California, San Francisco. “We are very excited about recent developments and new therapies for PBC, but we always want to think about the patients’ experience of their disease.”

PBC can have a significant impact on quality of life, as many patients experience bothersome symptoms, as well as concomitant autoimmune disorders. Common symptoms such as fatigue, pruritus, anxiety, depression, and inability to sleep can impair daily activities and may lead to social dysfunction. “Pruritus is one of the most troublesome and undertreated symptoms in PBC,” Tana remarked. “You want to make sure that you are asking [patients] these questions – how does itching interfere with your lifestyle, would you like treatment for it? Not all patients do, but it is important to ask and offer.” Options for managing pruritus, typically in a stepwise approach, include cholestyramine, followed by opioid antagonists, sertraline, and salvage therapies such as plasmapheresis and ultraviolet light therapy. 

Fatigue, a common symptom in patients with PBC, raises another therapeutic conundrum. The TrACE approach can be used to “treat the treatable,” address any contributors to fatigue, help patients develop coping strategies, and understand the impact of fatigue on their lives. “A strong therapeutic relationship is invaluable in the management of PBC,” Tana noted. “Always keep in mind patients’ quality of life and extrahepatic manifestations.” The management of PBC should include the continuous assessment and management of symptoms, including extrahepatic manifestations such as dyslipidemia and metabolic bone disease, with treatment regimens tailored to the presence of symptoms. 

“PBC, like many chronic liver diseases, is a disease that can be well managed with a structured approach,” Tana added. “We now have more options than ever to treat our patients with PBC, and more are on the horizon.” Novel PPAR agonists elafibranor and seladelpar have shown promise as second-line therapies for PBC in patients who have had an inadequate response to or intolerance of ursodeoxycholic acid (UDCA).

Results from the RESPONSE trial showed that the benefit of seladelpar extended beyond improvements in biochemical markers, demonstrating a significant improvement in pruritus. While neither agent is recommended for patients with decompensated cirrhosis, the recently approved therapies may slow disease progression and effectively control symptoms for many patients with PBC. 

“There are changes afoot in the world of PBC,” Tana said. “The current paradigm that we have used for many years is securing a diagnosis, starting treatment, assessing response at 12 months, and then adding second-line therapy and managing symptoms. However, a new paradigm can be envisioned using targeted therapies individualized to particular patient profiles, and tailoring care throughout the course of the patient’s disease, and then a vision of, perhaps, completely normal liver tests and a normal quality of life, abolishing the need for transplantation and, ideally, a cure.” Early intervention may be key to improving response to therapy as well as outcomes. Some experts have advocated for assessment of the treatment response at an earlier timepoint, which could prompt the initiation of second-line therapies as early as 6 months after starting treatment with UDCA, if needed.  

For patients with advanced disease, who experience progressive fibrosis and complications, risk stratification is a key component of PBC management. While liver stiffness measurements and biochemical responses may often follow divergent trajectories in PBC, liver stiffness values greater than 10 kPa strongly predict liver-related events, and may be more sensitive predictors than biochemical trends in this population. Assessment and staging of fibrosis should be performed at baseline and during monitoring, ideally every 2 years, Tana added. Biochemical measurements (eg, albumin, bilirubin, alkaline phosphatase levels) and liver stiffness assessment by transient elastography are valuable tools that can help identify patients with advanced PBC who can benefit from immediate intervention.