Ursodeoxycholic Acid Therapy and Liver Transplant-free Survival in Patients with Primary Biliary Cholangitis

BACKGROUND AND AIMS: The clinical efficacy of ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) remains subject to debate as definitive randomized controlled trials are lacking. We aimed to determine whether UDCA prolongs transplantation (LT) free survival in PBC. METHODS: This international cohort study included patients from the Global PBC Study Group database, originating from 8 countries in Europe and North America. Both UDCA-treated and untreated patients were included. LT and death were assessed as a combined endpoint through Cox regression analyses, with inverse probability of treatment-weighing (IPTW). RESULTS: In the 3902 patients included, the mean (SD) age was 54.3 (11.9) years, 3552 patients (94.0%) were female, 3529 patients (90.4%) were treated with UDCA and 373 patients (9.6%) were not treated. The median (IQR) follow-up was 7.8 (4.1-12.1) years. In total, 721 UDCA-treated patients and 145 untreated patients died or underwent LT. After IPTW, the 10-year cumulative LT-free survival was 79.7% (95%CI 78.1-81.2) among UDCA-treated patients and 60.7% (95%CI 58.2-63.4) among untreated patients (P<0.001). UDCA was associated with a statistically significant reduced risk of LT or death (Hazard Ratio [HR] 0.46, 95%CI 0.40-0.52, P<0.001). The HR remained statistically significant in all stages of disease. Patients classified as inadequate biochemical responders after one year of UDCA had a lower risk of LT or death than patients who were not treated (adjusted HR 0.56, 95%CI 0.45-0.69, P