Hepatology · Article 198

Which Second-Line Therapies Should Be Used for Primary Biliary Cholangitis?

PBC second-line therapy requires a structured, evidence-based clinical approach. This review summarizes the key diagnostic, management, monitoring and decision points for gastroenterology and hepatology practice.

PBC second-line therapy clinical reference — Related free clinical resource: Guideline-Based Management in Hepatology.

PBC second-line therapy: practical clinical approach

This page focuses on PBC second-line therapy with emphasis on decisions that change patient care, common pitfalls, and the current evidence base.

External guidance for PBC second-line therapy

Clinical takeaway: For PBC second-line therapy, decisions should integrate current guidelines, patient-specific risk, and the evidence summarized below.

Answer first: The second-line PBC landscape changed rapidly in 2024–2026. Elafibranor and seladelpar, both PPAR-targeted therapies, are approved options for adults with inadequate response or intolerance to UDCA in appropriate settings. Seladelpar also has evidence for improvement in cholestatic pruritus. Obeticholic acid was withdrawn from the U.S. market in 2025, so it should no longer be treated as the default U.S. second-line option. Fibrates, particularly bezafibrate in regions where available, remain an off-label evidence-supported strategy but require renal, hepatic and muscle monitoring.

Reassess the baseline before adding therapy

Confirm diagnosis, UDCA dose, adherence, fibrosis stage and biochemical risk.

New PPAR therapies are now central

Elafibranor and seladelpar provide approved alternatives for inadequate UDCA response.

Cirrhosis changes safety

Decompensated disease requires specialist management; drug labeling and hepatic impairment restrictions must be respected.

Practical clinical algorithm

1. Confirm inadequate UDCA response after appropriate dosing.

2. Stage liver disease and identify decompensation.

3. Discuss approved second-line options such as elafibranor or seladelpar.

4. Consider fibrates where appropriate and supported locally.

5. Monitor ALP, bilirubin, symptoms and adverse effects.

6. Reassess transplant risk in advanced disease rather than endlessly adding drugs.

Common mistakes to avoid

Continuing to recommend withdrawn U.S. obeticholic acid as routine therapy.
Adding a drug before confirming UDCA adherence.
Ignoring decompensated cirrhosis restrictions.
Treating pruritus response as equivalent to disease-modifying response.
Failing to monitor renal/muscle effects with fibrates.

Trainee takeaway

PBC second-line therapy is now a PPAR-centered field; clinicians should update older algorithms that still place obeticholic acid at the center.

Frequently asked questions

Which new drugs are approved?

Elafibranor and seladelpar are approved second-line options in the U.S.

Is obeticholic acid still available in the U.S.?

It was withdrawn from the U.S. market in 2025.

Do fibrates still have a role?

Yes, off-label in selected patients and depending on regional practice.

References

1. Thomson ABR. Clinical Pharmacology, Physiology and Pathophysiology: Gastroenterology, Hepatology, and Pancreaticobiliary Disorders. CAPstone Academic Publishers; 2024.

2. Thomson ABR. Guideline-Based Management in Hepatology. CAPstone Academic Publishers; 2015.

3. Kowdley KV, et al. Efficacy and Safety of Elafibranor in Primary Biliary Cholangitis. N Engl J Med. 2024.

4. Hirschfield GM, et al. Seladelpar in Patients with Primary Biliary Cholangitis. N Engl J Med. 2024.

5. AASLD. Statement Acknowledging Withdrawal of Obeticholic Acid for PBC. November 6, 2025.

Educational content only. Clinical decisions should incorporate the individual patient, local resources, product labeling, and the most current applicable guideline or regulatory information.

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