Liver Lineup: Innovations in Cholestatic Disease Management, With Kris Kowdley, MD

In this episode of Liver Lineup: Updates & Unfiltered Insights, Nancy Reau, MD, sits down with Kris Kowdley, MD, to discuss evolving approaches in cholestatic liver disease, with a particular focus on primary biliary cholangitis (PBC).

The conversation begins with how treatment goals have shifted from partial biochemical response to striving for full normalization of alkaline phosphatase and bilirubin, changes supported by recent global data showing improved long-term outcomes when patients achieve complete biochemical remission.

Kowdley highlights how these evolving targets are shaping clinical practice and guideline development, including the growing push to evaluate UDCA response at 6 months rather than 1 year, potentially expediting decisions about second-line therapy. The discussion also underscores the importance of incorporating staging tools such as transient elastography, which has shown promise as a biomarker and surrogate endpoint for predicting clinical outcomes in PBC.

The duo highlights the recent voluntary withdrawal of obeticholic acid from the US market as another major inflection point for clinicians, raising questions about how to manage patients who had been stable on the therapy. Kowdley reviews available alternatives, including fibrates and recently approved peroxisome proliferator-activated receptor (PPAR) agonists elafibranor and seladelpar, and addresses practical considerations when transitioning patients to new regimens. Importantly, he notes the potential of combination or even triple therapy strategies to help more patients achieve complete biochemical response.

Beyond laboratory targets, the conversation emphasizes patient-centered outcomes such as fatigue and pruritus, symptoms that often have a profound impact on quality of life but have historically lacked effective treatment. The emerging role of ileal bile acid transporter (IBAT) inhibitors represents an encouraging step forward, offering rapid relief of pruritus in PBC and other cholestatic diseases, with clinical trials underway to expand their use.

The pair also discuss diagnosis, particularly in challenging AMA-negative cases. Kowdley shares insights on when to use biopsy, how transient elastography fits into the workup, and the emerging role of genetic testing for patients with atypical presentations or suspected hereditary cholestatic syndromes.

The episode closes with reminders about comprehensive management, including monitoring bone health and tailoring therapy to the individual patient’s disease stage, biochemical profile, and quality-of-life concerns.

Editors’ note: Reau has relevant disclosures with AbbVie, Gilead, Salix, Arbutus, and VIR. Kowdley has relevant disclosures with CymaBay, Genfit, Gilead, Intercept, Ipsen, Madrigal, Mirum, Pfizer, NovoNordisk, 89Bio, AbbVie, and others.

References

1. Brooks A. Intercept Voluntarily Withdraws Obeticholic Acid (Ocaliva) for PBC From US Market. HCPLive. September 11, 2025. Accessed September 18, 2025. https://www.hcplive.com/view/intercept-voluntarily-withdrawals-obeticholic-acid-ocaliva-for-pbc-from-us-market

2. Brooks, A. FDA Grants Accelerated Approval to Elafibranor (Iqirvo) for PBC. HCPLive. June 10, 2024. Accessed September 18, 2025. https://www.hcplive.com/view/fda-grants-accelerated-approval-to-elafibranor-iqirvo-for-pbc

3. Brooks, A. FDA Grants Accelerated Approval to Seladelpar (Livdelzi) for Primary Biliary Cholangitis. HCPLive. August 14, 2024. Accessed September 18, 2025. https://www.hcplive.com/view/fda-grants-accelerated-approval-to-seladelpar-livdelzi-for-primary-biliary-cholangitis