When ursodiol isn't enough: New guidance on treating PBC

Clinical takeaway: Ursodeoxycholic acid (ursodiol; UDCA) remains the foundation of primary biliary cholangitis (PBC) treatment and should be offered at diagnosis, but clinicians should reassess biochemical response within 6-12 months and consider earlier escalation in higher-risk patients. The guideline emphasizes risk-based management using liver stiffness measurement and newly approved second-line therapies, particularly PPAR agonists, for patients with inadequate response or UDCA intolerance.

The first medication-focused joint guideline from the American Gastroenterological Association and American Association for the Study of Liver Diseases addresses major changes in the PBC treatment landscape, including the availability of newer therapies and the withdrawal of obeticholic acid from the US market in 2025. The document focuses on six key clinical questions spanning diagnosis, risk stratification, second-line treatment, pruritus management, and post-transplant care.

The guideline strongly recommends UDCA as first-line therapy for all patients with PBC. At doses of 13-15 mg/kg/day, UDCA improves liver biochemistries, slows histologic progression, and improves transplant-free survival. Importantly, the authors advise continuing UDCA even when alkaline phosphatase (ALP) remains elevated, as partial biochemical improvement is still associated with clinical benefit.

A central update is the recommendation to use peroxisome proliferator-activated receptor (PPAR) agonists as second-line therapy in patients with inadequate response or intolerance to UDCA. The guideline suggests elafibranor or seladelpar as add-on therapy for incomplete responders or as monotherapy when UDCA cannot be tolerated. Response should generally be assessed after at least 6 months and no later than 12 months of UDCA treatment, with normalization of ALP considered the ideal target when achievable.

The societies also endorse liver stiffness measurement, preferably with vibration-controlled transient elastography, to improve risk stratification. Patients with liver stiffness measurements ≥10 kPa are considered at higher risk for adverse outcomes and may warrant closer monitoring and consideration of treatment escalation.

For diagnosis, the guideline recommends testing for anti-sp100 and anti-gp210 antibodies in patients with suspected PBC who are antimitochondrial antibody negative. Positive results may help establish the diagnosis and avoid liver biopsy in some patients.

Pruritus receives dedicated attention. The guideline suggests linerixibat as an option for patients with moderate-to-severe cholestatic pruritus, while emphasizing shared decision-making because benefits must be weighed against common gastrointestinal adverse effects, including diarrhea and abdominal pain.

For liver transplant recipients, the societies suggest prophylactic UDCA beginning as soon as possible after transplantation to reduce the risk of recurrent PBC and graft failure.

“This guideline provides clinicians and patients with practical, evidence-based guidance on navigating challenging diagnoses and selecting appropriate second-line therapies as today’s treatment options continue to evolve,” said guideline author David Assis, MD. The authors note that management decisions should increasingly be individualized based on disease severity, symptoms, liver stiffness, and patient preferences.

What’s changed

• First AGA/AASLD guideline focused specifically on medication-related management decisions in PBC.
• Recommends anti-sp100 and anti-gp210 antibody testing to aid diagnosis of AMA-negative PBC before liver biopsy.
• Formally endorses liver stiffness measurement for prognostication and risk stratification.
• Suggests PPAR agonists (elafibranor, seladelpar) as preferred second-line options after inadequate UDCA response or intolerance.
• Introduces guidance on linerixibat, the first FDA-approved therapy specifically for PBC-related pruritus.
• Recommends post-transplant UDCA prophylaxis to reduce recurrent PBC and graft failure.

Source: Levy C, et al. (2026 Oct 22) Gastroenterology. AGA/AASLD Clinical Practice Guideline on Management of Primary Biliary Cholangitis