Ursodeoxycholic acid treatment-induced GLOBE score changes are associated with liver transplantation-free survival in patients with primary biliary cholangitis

Background: Treatment of primary biliary cholangitis (PBC) can improve the GLOBE score. We aimed to assess the association between changes in the GLOBE score (ΔGLOBE) and liver transplantation (LT)-free survival in patients with PBC who were treated with ursodeoxycholic acid (UDCA). Methods: Among UDCA-treated patients within the Global PBC cohort, the association between ΔGLOBE ( 0-1 : during first year of UDCA, 1-2 : during second year) and the risk of LT or death was assessed through Cox regression analyses. Results: Overall, 3775 UDCA-treated patients were included; 3424 [90.7%] were female, median age 54.0 (IQR 45.9-62.4) years and median baseline GLOBE score was 0.25 (IQR -0.47 - 0.96). During a median follow-up of 7.2 (IQR 3.7-11.5) years, 730 patients reached the combined endpoint of LT or death. Median ΔGLOBE 0-1 was -0.27 (IQR -0.56 - 0.02). Cox regression analyses, adjusted for pretreatment GLOBE score and ΔGLOBE 0-12 , showed that ΔGLOBE was associated with LT or death (adjusted HR 2.28, 95%CI 1.81-2.87, p <0.001). The interaction between baseline GLOBE score and ΔGLOBE 0-1 was not statistically significant ( p =0.296). The ΔGLOBE 1-2 was associated with LT or death (adjusted HR 2.19, 95%CI 1.67-2.86, p<0.001), independently from the baseline GLOBE score and de change in GLOBE score during the first year of UDCA. Conclusion: UDCA-induced changes in the GLOBE score were significantly associated with LT-free survival in patients with PBC. While the relative risk reduction of LT or death was stable, the absolute risk reduction was heavily dependent on the baseline prognosis of the patient.