The GLOBE score identifies PBC patients at increased risk of liver transplantation or death in different age-categories over time

Background and Aims: The GLOBE score differentiates PBC patients into high- and low risk groups for death or liver transplantation after 1 year of UDCA therapy using age-specific thresholds. We sought to determine whether the GLOBE score is predictive for death and liver transplantation when used over time in patients of different age- categories. Methods: Data from the Global PBC Study Group was used. Every 6 months starting at 1 yearof UDCA therapy we identified patients who passed their age-specific GLOBE score thresholds (aGLOBE-t) (ages <45, 45\u201352, 52\u201358, 58\u201366, and 6566 years, with thresholds 12 0.52, 0.01, 0.60, 1.01 and 1.69, respectively). For those passing their aGLOBE-t and those patients who did not, time to a combined endpoint of liver transplantation (LT) and death were compared with POSTER PRESENTATIONS JOURNAL OF HEPATOLOGY Journal of Hepatology 2017 vol. 66 | S543 \u2013 S750 \ua9 2017 All rights reserved. Cox-proportional hazards analysis with aGLOBE-t as a time-depend- ent covariate. Results: A total of 4340 UDCA-treated PBC patients were included, 924 (21.3%), 885 (20.4%), 875 (20.2%), 876 (20.2%), 780 (18%) in age categories <45 (A), 45 \u2013 52 (B), 52 \u2013 58 (C), 58 \u2013 66 (D), and 65 66 (E), respectively. At 12 months of UDCA therapy a total of 1244 (28.7%) patients passed their aGLOBE-t, 375 (40.6%), 279 (31.5%), 207 (23.7%), 208 (23.7%), and 175 (22.4%) in age categories A-E, respectively. Within the following 10 years there were an additional 841 (46.7%) patients that passed their aGLOBE-t, 183 (41.6%), 163 (45.7%), 172 (46.5%), 156 (41.1%), and 167 (40.6%) within age categories A-E, respectively (Fig 1.) The effect (time-dependent hazard ratio (HR)) on the clinical endpoint (death or LT) of passing the aGLOBE-t during follow-up, in patients that were characterized as low risk patients at 12 months of UDCA therapy, but passed theiraGLOBE-t during further follow-up, was HR 4.9 (95% confidence interval [CI]: 1.4 \u2013 17.2), HR 3.7 (1.1 \u2013 9.7), 4.3 (2.3 \u2013 8.1), 3.7 (2.2 \u2013 6.0) and 3.0 (2.1 \u2013 4.3) in age categories A-E, respectively. Conclusions: Patients of different age-categories with a beneficial GLOBE score at 12 months of UDCA therapy are at significant risk of death or LT when they pass their age-specific GLOBE score threshold during further follow-u

Increase in age at diagnosis of primary biliary cholangitis over the last 40 years

Background and Aims: In recent decades, primary biliary cholangitis (PBC) patients tend to present at an earlier disease stage. However, calendar time trends in age at diagnosis, biochemical response to ursodeoxycholic (UDCA) and clinical outcomes have not been fully characterized. The current study aims to describe calendar time trends in a large international cohort of PBC patients and provide important information on the evolution of PBC over the years. Methods: Patient data was retrieved from the Global PBC Study group database, comprising of PBC patients from 16 centers across Europe and North America. Patients were subdivided into 10-year cohorts according to their year of diagnosis: 1970-1980(n=144), 1980-1990(n=868), 1990-2000(n=1858), 2000-2010(n=1966), >=2010(n=255). Calendar time trends in age at diagnosis, biochemical response to UDCA, biochemical and histological disease stage, and clinical outcomes (death or liver transplantation) were assessed in each 10-year cohort. Results: A total of 5091 PBC patients were included, 4507(90.7%) were AMA positive and median follow-up time was 7.2 years (IQR 3.6-11.5). The proportion of male patients increased from 8.3% in the 1970\u2019s to 13.3% in 2010. Age at diagnosis increased incrementally from the 1970\u2019s (mean 46.9, SD 10.1) to 2010 (mean 57.3, SD 12.1, p<0.001), irrespective of biochemical disease stage (Figure 1). Additionally, there was an increase in the number of patients presenting with an earlier disease stage, both biochemically and histologically, p<0.001. The proportion of patients with an early biochemical disease stage in the 1970\u2019s and after 2010 was 41% and 69.9%, respectively. In accordance, patients were more likely to respond to UDCA according to the Paris-I criteria, 51.7% vs. 71% (p<0.001). An increase in response may account for the improved 10-year transplant-free survival between patients from the 1970\u2019s and 2010, 48.1% and 79.7%, respectively (p=0.004). Conclusions: Patient and disease characteristics of PBC at diagnosis have changed over the years, most notably by an increase in age at diagnosis and increased proportion of males. Furthermore, patients tend to present with milder biochemical disease stage regardless of age and gender

Ursodeoxycholic Acid Treatment-Induced GLOBE Score Changes Are Associated With Liver Transplantation-Free Survival in Patients With Primary Biliary Cholangitis

INTRODUCTION: 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 (ΔGLOBE 0-1 : during the first year of UDCA, ΔGLOBE 1-2 : during the second year) and the risk of LT or death was assessed through Cox regression analyses. RESULTS: Overall, 3,775 UDCA-treated patients were included; 3,424 (90.7%) were female, the median age was 54.0 (interquartile range [IQR] 45.9-62.4) years, and the median baseline GLOBE score was 0.25 (IQR -0.47 to 0.96). During a median follow-up of 7.2 (IQR 3.7-11.5) years, 730 patients reached the combined end point of LT or death. The median ΔGLOBE 0-1 was -0.27 (IQR -0.56 to 0.02). Cox regression analyses, adjusted for pretreatment GLOBE score and ΔGLOBE 0-12 , showed that ΔGLOBE was associated with LT or death (adjusted hazard ratio 2.28, 95% confidence interval 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 hazard ratio 2.19, 95% confidence interval 1.67-2.86, P < 0.001), independently from the baseline GLOBE score and the change in GLOBE score during the first year of UDCA. DISCUSSION: 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

Increase in age at diagnosis of primary biliary cholangitis over the last 40 years

status: publishe