A. Sidney Barritt, MD, is a tenured associate professor and the director of hepatology in the UNC liver center at the University of North Carolina.

A. Sidney Barritt, MD

Closing Gaps in PBC Care With Emerging and Established Second-Line Treatments

 has undergone a meaningful transformation in recent years, offering new optimism for a disease long defined by limited treatment options.

While ursodeoxycholic acid remains the cornerstone of first-line therapy, a substantial proportion of patients fail to achieve an adequate biochemical response, placing them at continued risk for disease progression. In an interview with HCPLive, A. Sidney Barritt, MD, a tenured associate professor and the director of hepatology in the UNC liver center at the University of North Carolina, and Frances Lee, MD, an assistant professor of medicine in the division of liver diseases at Mount Sinai, discuss how the arrival of multiple second-line agents is reshaping PBC management, redefining treatment goals, and prompting clinicians to think more broadly about both outcomes and quality of life.

Barritt emphasized that for decades, the 20% to 30% of patients who did not respond adequately to ursodeoxycholic acid represented a critical unmet need. The availability of second-line therapies has changed that equation, with the introduction of seladelpar (Livdelzi) and elafibranor (Iqirvo) allowing clinicians to help more patients achieve normalization of alkaline phosphatase and meaningful reductions in bilirubin. These biochemical improvements, he noted, are closely linked to reduced risks of cirrhosis, hepatic decompensation, and liver transplantation. With better tools now available, he says there is a real opportunity to slow the pace of disease progression for many patients.

Lee echoed this perspective, underscoring the significance of having multiple second-line options for patients with an incomplete response to first-line therapy. She framed these advances as a source of renewed hope, not only for controlling disease activity but also for improving patients’ day-to-day lives.

Despite this progress, both experts highlighted persistent gaps in PBC care. Barritt pointed to delays in diagnosis as a major issue, noting that abnormal alkaline phosphatase levels are often present for years before PBC is recognized. Earlier identification, followed by prompt initiation and optimization of therapy, remains essential to improving outcomes.

Lee focused on the importance of addressing quality-of-life concerns, such as pruritus and fatigue, which can be profoundly disabling yet are frequently underrecognized. She also noted that careful symptom assessment may uncover concomitant autoimmune conditions that warrant targeted management.

Looking ahead, both experts expressed enthusiasm for ongoing research and emerging therapies, including additional PPAR agonists, FXR-targeting agents, and treatments aimed specifically at symptom relief. Both stressed that clinicians should adopt more ambitious biochemical targets, striving for alkaline phosphatase levels as close to normal as possible and aggressive use of second-line therapies when goals are not met. With an expanding therapeutic arsenal, they say the focus in PBC is shifting toward true disease optimization rather than acceptance of partial control.

Editors’ Note: Barritt reports relevant disclosures with Mirum, Madrigal, Target RWE, Boehringer Ingelheim, Merck, and Mallinckrodt. Lee reports no relevant disclosures.

Brooks A. FDA Grants Accelerated Approval to Elafibranor (Iqirvo) for PBC. HCPLive. June 10, 2024. Accessed January 22, 2026. 

https://www.hcplive.com/view/fda-grants-accelerated-approval-to-elafibranor-iqirvo-for-pbc

Brooks A. FDA Grants Accelerated Approval to Seladelpar (Livdelzi) for Primary Biliary Cholangitis. HCPLive. August 14, 2024. Accessed January 22, 2026. 

https://www.hcplive.com/view/fda-grants-accelerated-approval-to-seladelpar-livdelzi-for-primary-biliary-cholangitis

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A pair of hepatology experts discuss the shifting therapeutic landscape in PBC, lingering unmet needs, and where the field may be heading next.

A. Sidney Barritt, MD

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