When to Start Second-Line Therapy in PBC, With Kris Kowdley, MD

Clinicians caring for patients with primary biliary cholangitis (PBC) should take a second look at alkaline phosphatase (ALP) levels, because normalization is now achievable in a high proportion of patients, according to Kris Kowdley, MD, director of Liver Institute Northwest.

“I would encourage everyone who cares for patients with PBC to really look at that alkaline phosphatase and ask: Is this a patient that would benefit from normalization of alkaline phosphatase,” Kowdley told HCPLive at The Liver Meeting 2026 in Denver, Colorado.

His comments follow late-breaking phase 3 ELSPIRE data, in which elafibranor (Iqirvo) normalized ALP in 85.3% of patients with ALP between 1 and 1.67 times the upper limit of normal (ULN) despite ursodeoxycholic acid, compared with 23.3% receiving placebo.1

How Should Clinicians Decide on Second-Line Therapy?

Kowdley emphasizes that starting second-line therapy is a shared decision between patient and physician. Clear candidates include patients with moderate to advanced fibrosis, such as liver stiffness above 8 to 10 kPa, ALP well above 1.67 times ULN, or bilirubin above 0.6 times ULN. Global PBC Study Group data identified that bilirubin threshold as the best predictor of transplant or death, with 10-year survival of 91.3% at or below it vs 79.2% above it.2 He also weighs age at diagnosis, symptoms such as itch and fatigue, and disease stage.

Who Might Be Overlooked?

Because many patients with PBC are seen only once or twice a year, Kowdley says those who do not raise symptoms or treatment goals may be missed.

Watch the full interview to hear Kowdley discuss how he individualizes care, why genetic cholestatic diseases may play a broader role than once thought, and the emerging therapies he is watching.

References

1. Kowdley K, Lawitz E, Bowlus C, et al. Elafibranor to normalize alkaline phosphatase in patients with primary biliary cholangitis and incomplete response to ursodeoxycholic acid: results from the phase III randomized controlled ELSPIRE trial. Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO.
2. Murillo Perez CF, Harms MH, Lindor KD, et al; Global PBC Study Group. Goals of treatment for improved survival in primary biliary cholangitis: treatment target should be bilirubin within the normal range and normalization of alkaline phosphatase. Am J Gastroenterol. 2020;115(7):1066-1074. doi:10.14309/ajg.0000000000000557