Development and Validation of a Scoring System to Predict Outcomes of Patients With Primary Biliary Cirrhosis Receiving Ursodeoxycholic Acid Therapy

BACKGROUND & AIMS: Approaches to risk stratification for patients with primary biliary cirrhosis (PBC) are limited, single-center based, and often dichotomous. We aimed to develop and validate a better model for determining prognoses of patients with PBC.

METHODS: We performed an international, multicenter meta-analysis of 4119 patients with PBC treated with ursodeoxycholic acid (UDCA) at liver centers in 8 European and North American countries. Patients were randomly assigned to derivation (n=2488, 60%) and validation cohorts (n=1631, 40%). A risk score (GLOBE score) to predict transplantation-free survival was developed and validated with univariate and multivariable Cox regression analyses using clinical and biochemical variables obtained after 1 y UDCA therapy. Risk score outcomes were compared with the survival of age-, sex-, and calendar time-matched members of the general population. The prognostic ability of the GLOBE score was evaluated alongside those of the Barcelona, Paris-1, Rotterdam, Toronto, and Paris-2 criteria.

RESULTS: Age (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.04-1.06; P<.0001); levels of bilirubin (HR, 2.56; 95% CI, 2.22-2.95; P<.0001), albumin (HR, 0.10; 95% CI, 0.05-0.24; P<.0001), and alkaline phosphatase (HR, 1.40; 95% CI, 1.18-1.67; P=.0002); and platelet count (HR/10 units decrease, 0.97; 95% CI, 0.96-0.99; P<.0001) were all independently associated with death or liver transplantation (C statistic derivation, 0.81; 95% CI, 0.79-0.83, and validation cohort, 0.82; 95% CI, 0.79-0.84). Patients with risk scores >0.30 had significantly shorter times of transplant-free survival than matched healthy individuals (P<.0001). The GLOBE score identified patients who would survive for 5 y and 10 y (responders) with positive predictive values of 98% and 88%, respectively. Up to 22% and 21% of events and non-events, respectively, 10 y after initiation of treatment were correctly reclassified in comparison with earlier proposed criteria. In subgroups of patients <45 y, 45-52 y, 52-58 y, 58-66 y, and ≥66 y old, age-specific GLOBE-score thresholds beyond which survival significantly deviated from matched healthy individuals were -0.52, 0.01, 0.60, 1.01 and 1.69, respectively. Transplant-free survival could still be accurately calculated by the GLOBE score with laboratory values collected at 2-5 y after treatment.

CONCLUSIONS: We developed and validated scoring system (the GLOBE score) to predict transplant-free survival of UDCA-treated patients with PBC. This score might be used to select strategies for treatment and care.