University of Birmingham 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). 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. Patients were derived from the Global PBC Study Group database. This study group is an international and multicenter collaboration between 15 liver centers from 8 North American and European countries, which combined individual patient data from major long-term follow-up cohorts. Most cohorts included prospectively collected follow-up data. All patients had an established diagnosis of PBC 2, 3 and characteristics of the study population have been previously described elsewhere. 18 For the current study only those patients treated with UDCA were included. Patients were excluded if follow-up data were insufficient or unavailable, the start date of treatment or the exact date of major clinical events was unknown or in case of concomitant liver disease. Collected clinical and laboratory data included gender, age, PBC diagnosis, liver histology, treatment (type of medication, dosage and duration), duration and last date of follow-up, baseline antimitochondrial antibody status, baseline and yearly laboratory values (serum alkaline phosphatase, total bilirubin, albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and platelets and outcomes (death and cause of death, liver transplantation, hepatocellular carcinoma, ascites and variceal bleeding). the predictive ability of the score was satisfactory with a C statistic of 0.81 (95% CI 0.76-0.86) in the early stage subgroup and 0.78 (95% CI 0.74-0.83) in the late stage. Comparable results were found when repeating these analyses in the validation cohort; with a C statistic in the early stage (n=448) of 0.85 (0.79-0.91) and in the late stage (n=212) of 0.79 (0.72-0.86).