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Updates in PBC
Updates in Primary Biliary Cholangitis (PBC) Management From EASL 2025 

Released: June 13, 2025

Expiration: December 12, 2025

Aparna Goel
Aparna Goel, MD
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Key Takeaways

•    Assessing response to UDCA as early as 6 months may identify who should move on to second-line therapy.
•    New data on different second-line PPARs give insights on efficacy in hepatic and extrahepatic manifestations of primary biliary cholangitis and safety in bone health.
•    Statins may have a role in managing chronic liver disease beyond lipid-lowering.  


Recent presentations at the European Association for the Study of the Liver 2025 provided meaningful updates for the evolving management of primary biliary cholangitis (PBC), focusing on optimizing early response assessment, advancing second-line therapies, and addressing systemic complications. These developments carry significant implications for improving outcomes in patients with suboptimal responses to ursodeoxycholic acid (UDCA).

Early Response Assessment
A 25-year retrospective analysis of 155 patients revealed strong predictors of complete biochemical response (CBR) to UDCA at 12 months and at long-term follow-up (median 10 years). Specifically, achieving the Toronto criteria at 6 months (OR: 81) and reaching CBR at 12 months (OR: 55) were highly predictive of CBR at end of follow-up.

By contrast, the presence of cirrhosis at baseline significantly reduced the likelihood of achieving CBR (OR: 0.19).

Of note, none of the patients who failed to meet Toronto criteria at 6 months achieved CBR by the end of the follow-up period. These data reinforce a time-sensitive approach to identify patients who may benefit from earlier initiation of second-line therapy. I think that these data support moving away from the traditional 12-month reassessment.

Second-Line PPAR Efficacy ...
Data analysis from the RESPONSE and ASSURE trials demonstrated that the peroxisome proliferator–activated receptor (PPAR) agonist seladelpar was associated with early and sustained GLOBE score improvements from baseline through 24 months of treatment. These improvements were primarily driven by reductions in alkaline phosphatase and total bilirubin, both well-established prognostic markers in PBC. The corresponding predicted transplant-free survival showed consistent improvement at 3, 12, and 24 months in the seladelpar arm, whereas no meaningful change was observed in the placebo arm. These findings underscore seladelpar’s potential as a disease-modifying therapy.

Complementing these findings, pooled data from the ENHANCE and RESPONSE studies demonstrated that in patients with moderate to severe pruritus, seladelpar was associated with significant improvement.

This dual impact on clinical symptoms and biochemical markers highlights the PPAR agonist’s potential role in treating both the hepatic and extrahepatic manifestations of PBC. 

... And Safety
For both FDA-approved PPAR agonists, seladelpar and elafibranor, there is potential for increased risk of fractures noted in the prescribing information. At EASL 2025, a post-hoc analysis examined bone health and outcomes in the ELATIVE trial of elafibranor. At baseline, a higher percentage of patients in the elafibranor arm had a history of osteoporosis compared with patients in the placebo arm (19% vs 3%). Higher proportions of patients in the elafibranor arm were also receiving bisphosphonates, vitamin D, and calcium supplementation compared with those in the placebo group. 

Baseline and Week 52 assessments of bone mineral density (BMD) and bone turnover markers—C-terminal telopeptide of type 1 collagen and amino-terminal propeptide of type 1 procollagen—were available for approximately half of the study population. No significant changes were observed in BMD at the femoral neck and lumbar spine in either arm. A significant difference in change from baseline BMD between the elafibranor and placebo groups was observed in the total hip region, with slight increases in BMD with elafibranor and decreases in BMD with placebo.

Changes in bone turnover markers were comparable across both groups throughout the study. Of the 7 fractures reported in the elafibranor group, 6 were associated with trauma.

I think that these findings help address concerns regarding the use of elafibranor in patients with PBC, particularly given the importance of bone health as a clinical consideration.

Statins for Chronic Liver Disease
Finally, compelling data from a retrospective cohort study of 466 patients with PBC highlighted the underappreciated benefit of statins. In patients with noncirrhotic PBC, statin use for more than 12 months was associated with reduced progression to cirrhosis (HR: 0.48) and significantly lower all-cause mortality (HR: 0.28), both liver and nonliver related. This finding suggests that statins may confer hepatoprotective effects beyond lipid-lowering, meriting consideration in clinical practice.

Your Thoughts
Do you plan to make changes to your practice based on this new data? Leave a comment to join the discussion!