Ask AI
Back Back
PBC Second Line Therapy
Avoid These Common Misconceptions and Mistakes About PBC Second-Line PBC Therapy

Released: February 17, 2026

Gideon Hirschfield
Gideon Hirschfield, MA, MB BChir, FRCP, PhD
Activity Information

Activity

Progress
1
Course Completed
Continue
Key Takeaways
  • When deciding on escalation to second-line therapy, treat primary biliary cholangitis to ideal targets, aiming for normal alkaline phosphatase, normal bilirubin, and no symptoms. 
  • Follow response through biochemistry, symptom improvement, and longer-term disease indicators such as liver stiffness trends.

Living with primary biliary cholangitis (PBC) now means there are lots of opportunities to improve disease control and prevent end-stage liver disease. I think 1 misconception about PBC is that not everyone needs second-line therapy if they meet current biochemical response criteria, or that it is okay to use slightly outdated treatment goals, which may be adequate but not ideal. 

Instead, I would like people to move away from the idea that there is no rush to get treatment and no need to aim high in managing PBC. In contrast, I want people to think about the ideal treatment goals of normal bilirubin, normal alkaline phosphatase (ALP), and no symptoms, including pruritus. Every time you see a patient with PBC, think about how you can reach these goals with the available treatments.

In the US, these treatments are ursodeoxycholic acid (UDCA) and the 2 next-generation PPAR agonists elafibranor and seladelpar, which are add-on therapies to UDCA. A mistake I sometimes see is to stop UDCA when starting second-line therapy; this is not recommended.

In the future, there may also be treatments available that will target pruritus, which will become very important for people with reduced quality of life because of their symptoms.

Moving to Second-line PBC Therapy
In looking at response to first-line therapy and determining the need for second-line therapy, the healthcare professional should be considering what they can most confidently offer to their patient to seek normalization of ALP, stability and improvement in liver stiffness, and improvement in symptoms, particularly pruritus. Therefore, the simplest algorithm for PBC second-line therapy is to look at the patient’s biochemical response after 6-12 months of treatment with weight-based UDCA therapy and see what your patient needs to achieve an ideal treatment response. In patients whose biochemical response is not where it needs to be—meaning normal ALP, bilirubin, and no symptoms—consider the use of approved second-line agents in combination with UDCA.

Emerging Data on Improved Outcomes
We now have increased confidence that these targets mean something, that biochemical response on second-line therapy is associated with better outcomes.

All of the data we had initially were in patients treated with first-line UDCA, and this strongly supports that biochemistry is a good surrogate of outcome. We now have data, reported at this time as conference abstracts, showing that in patients treated with second-line obeticholic acid (no longer available in the US) or a fibrate, those who have an improvement in ALP have better clinical outcomes. These data support using biochemical treatment efficacy in assessing the impact of second-line therapy, supporting the goal of moving all appropriate patients towards an ideal response to their therapies.

Your Thoughts
When and why do you escalate beyond UDCA to second-line therapy? Share what typically triggers your move to second-line therapy and what barriers delay escalation in your practice.

Continue