AGA/AASLD joint guideline evaluates newer medications for primary biliary cholangitis

For the first time, a joint guideline from the American Gastroenterological Association (AGA) and American Association for the Study of Liver Diseases (AASLD) evaluates newer medications for primary biliary cholangitis (PBC), the most common cholestatic disease in adults. Published in Gastroenterology and HEPATOLOGY, the guideline provides evidence-based recommendations for diagnosis and treatment. 

The guideline addresses recent changes in the PBC treatment landscape and key challenges clinicians face, including diagnosing patients with less common antibody profiles, determining when to move beyond first-line therapy, and managing PBC-related itching. Because most people living with PBC are cared for by general gastroenterologists rather than hepatology specialists, the guideline is designed to ensure the broader GI community has access to the latest evidence and standards of care.

The PBC treatment landscape has changed significantly in the past five years, with new options for second-line therapy and the removal of a treatment that had been used for the past decade. 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." 

David N. Assis, MD, guideline author

This guideline complements AASLD's broader 2018 and 2021 PBC guidance, which addressed PBC care more comprehensively, with special emphasis on second-line treatment options. This is very timely given the withdrawal of obeticholic acid from the U.S. market late in 2025. 

Taken together, the recommendations support a personalized approach to PBC care that considers each patient's risk of disease progression, disease characteristics, symptoms, and preferences. The goal is to intervene early and tailor treatment over time to help slow disease progression and preserve quality of life. 

Key updates: 

AGA and AASLD offer six recommendations for the diagnosis and management of PBC: 

• Use SP100 and GP210 antibodies to help diagnose suspected PBC in those who test negative for antimitochondrial antibodies. These tests may help some patients avoid a liver biopsy.
• Use ursodeoxycholic acid as a first-line therapy for people with PBC.
• Measure liver stiffness to help determine the individual's risk of disease progression.
• Consider peroxisome proliferator-activated receptor agonists as add-on therapy for people with PBC who do not respond adequately to ursodeoxycholic acid or as an alternative for those who cannot tolerate it.
• Consider linerixibat for people with moderate-to-severe itching caused by PBC. Clinicians and patients should use shared decision-making to weigh potential benefits against factors such as gastrointestinal side effects, cost, and individual patient preferences.
• Use ursodeoxycholic acid prophylaxis after a liver transplant to reduce the risk of PBC recurrence and graft failure. 

The certainty of evidence supporting the recommendations ranges from moderate to very low, highlighting both advances in PBC care and areas that need more research. 

This guideline is not intended to be a comprehensive guide to managing every aspect of PBC. Instead, it answers specific clinical questions, such as when to use a particular drug or diagnostic test and how to use it appropriately. There are still many areas where we do not have enough evidence to make firm recommendations, underscoring the need for continued research." 

Marlyn Mayo, MD, guideline author 

Knowledge gaps and future directions 

Despite recent advances, significant questions remain about how best to manage PBC. 

More research is needed to understand how peroxisome proliferator-activated receptor agonists affect long-term outcomes, including mortality, transplant-free survival, and cirrhosis decompensation. Well-designed comparative studies examining these outcomes could help inform future recommendations. 

Additional research is also needed to determine how frequently elastography should be repeated to monitor patients and how clinicians should manage patients who do not respond to second-line therapy. Currently, evidence is insufficient to provide clear recommendations in these areas. Addressing these gaps will be important as diagnostic tools and treatment options continue to evolve. 

Understanding PBC

 Primary biliary cholangitis (PBC) is a long-term autoimmune liver disease. In PBC, the body's immune system mistakenly attacks small bile ducts inside the liver. Over time, this damage can make it harder for bile to flow normally. This can lead to scarring of the liver, called fibrosis, and in some people, may eventually cause cirrhosis, liver failure, or the need for a liver transplant. 

PBC is not caused by alcohol use, and it is not contagious. Most people with PBC can live for many years with proper treatment and monitoring. 

Early diagnosis and treatment with ursodeoxycholic acid can help slow disease progression, protect liver function, and improve long-term outcomes. Newer therapies may help people whose disease does not respond adequately to first-line treatment or who experience severe itching.