Shining Light on an Invisible Burden: Advances in Primary Biliary Cholangitis Care

New York, NY – At the 2025 Women’s Health Annual Visit (WHAV), hepatologists Dr. Gideon Hirschfield (Toronto General Hospital) and Dr. Marlyn Mayo (UT Southwestern Medical Center), who joined virtually, highlighted the evolving understanding and management of primary biliary cholangitis (PBC), a chronic autoimmune cholestatic liver disease that disproportionately affects women. Often called an “invisible” disease due to its subtle or nonspecific symptoms, PBC affects about one in 1,000 women over age 40, with more than 100,000 people currently living with the disease in the United States.

From Cirrhosis to Cholangitis: A Patient-Driven Name Change

Formerly known as primary biliary cirrhosis, the disease was renamed primary biliary cholangitis in 2015 following patient advocacy efforts to remove the stigma associated with the word “cirrhosis.” The change also reflects the ability to diagnose the disease earlier, when cirrhosis is not yet present. The new name was jointly adopted by hepatology and gastroenterology journals and recognized in ICD-10 coding soon after.

Who Is Affected?

Epidemiologic data show that 90% of PBC patients are women, with three-quarters diagnosed after age 50. Men do develop PBC, though usually at an older age and often with more advanced disease. Prevalence is increasing worldwide. Importantly, average survival after diagnosis has improved to about 20 years, up from 10 years in past decades.

Clinical Presentation: Symptoms and Diagnostic Clues

Many patients are asymptomatic at diagnosis, which contributes to under-recognition. When symptoms are present, the most common include:

• Fatigue (50–75%), often associated with brain fog, poor sleep, and reduced quality of life.

• Pruritus (up to 70%), which can be severe and life-altering, without correlating to disease severity.

• Sicca complex—dry eyes, dry mouth, and often vaginal dryness.

• Other features: hypercholesterolemia, osteoporosis, and fat-soluble vitamin deficiencies in advanced disease.

Diagnosis typically relies on:

• Persistent elevation of alkaline phosphatase and GGT.

• Antimitochondrial antibodies (AMA), present in >90% of cases.

• PBC-specific antinuclear antibodies (e.g., anti-gp210, anti-sp100) in AMA-negative patients.

• Liver biopsy is reserved for atypical cases.

Extrahepatic Associations

PBC frequently overlaps with other autoimmune conditions, including thyroid disease, rheumatoid arthritis, limited scleroderma, Sjögren’s syndrome, and inflammatory bowel disease. Osteoporosis and gallstones are also common, underscoring the need for broad patient monitoring.

Pathophysiology: Still Unclear

The cause of PBC remains unknown. Genetic predisposition, immune dysregulation, and environmental exposures likely interact. Examples cited include higher PBC prevalence among Nagasaki atomic bomb survivors and geographic overlap with toxic Superfund sites in New York.

Treatment: Expanding Beyond Ursodiol

For decades, ursodeoxycholic acid (UDCA) has been the mainstay of therapy, improving transplant-free survival. Patients with inadequate biochemical response—up to 40%—now have access to new agents:

• Elafibranor (a PPAR agonist, FDA-approved in 2024): Achieved a 51% composite response versus 4% with placebo and a 15% normalization of alkaline phosphatase at one year. However, it did not meet its primary endpoint for pruritus improvement.

• Seladelpar (a PPAR-delta agonist, also approved in 2024): Demonstrated both biochemical efficacy (61% composite response; 25% normalization) and clinically meaningful pruritus reduction, making it the first FDA-approved therapy to address both disease activity and symptom burden.

• Investigational therapies:IBAT inhibitors such as linerixibat have shown rapid, sustained, and statistically significant itch reduction in clinical trials and may soon add to symptom-focused management.

PBC in Women’s Health

Because a quarter of patients are diagnosed before age 50, PBC often intersects with reproductive health:

• UDCA is safe during conception, pregnancy, and breastfeeding.

• Bezafibrate can be used in the second or third trimester for severe cholestasis.

• Elafibranor and seladelpar should be avoided in pregnancy and require effective contraception.

• Hormone replacement therapy (HRT) and vaginal estrogens are generally safe unless advanced liver failure is present.

• Bone health should be proactively monitored, with bisphosphonates, Prolia, or IV therapies as needed.

Monitoring and Long-Term Care

For stable patients on UDCA with normalized labs, follow-up every 6–12 months is recommended, including liver function tests, thyroid screening, and bone density assessment. Elastography every 12–36 months helps track fibrosis progression. Patients with incomplete response, younger age at diagnosis, or advanced disease warrant closer specialist involvement.

Key Takeaways

• PBC is a common rare disease, affecting about 1 in 1,000 women over 40.

• Symptoms like fatigue and pruritus are common but often under-recognized.

• Diagnosis relies on alkaline phosphatase elevation and AMA positivity, with biopsy only in select cases.

• UDCA remains first-line, while elafibranor and seladelpar expand second-line options—seladelpar uniquely improving both liver tests and itch.

• Long-term care includes symptom management, monitoring for extrahepatic disease, and close attention to women’s health needs.

This educational session at the Women’s Health Annual Visit (WHAV Meeting) was funded by an independent educational grant from Gilead Sciences, Inc.