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

Willem J. Lammers, Gideon M. Hirschfield, Christophe Corpechot, Frederik Nevens, Keith D. Lindor, Harry L A Janssen, Annarosa Floreani, Cyriel Y. Ponsioen, Marlyn J. Mayo, Pietro Invernizzi, Pier M. Battezzati, Albert Parés, Andrew K. Burroughs, Andrew L. Mason, Kris V. Kowdley, Teru Kumagi, Maren H. Harms, Palak J. Trivedi, Raoul Poupon, Angela CheungAna Lleo, Llorenç Caballeria, Bettina E. Hansen, Henk R. Van Buuren

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Abstract

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 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 year of ursodeoxycholic acid 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 = 1.05; 95% confidence interval [CI]: 1.04-1.06; P <.0001); levels of bilirubin (hazard ratio = 2.56; 95% CI: 2.22-2.95; P <.0001), albumin (hazard ratio = 0.10; 95% CI: 0.05-0.24; P <.0001), and alkaline phosphatase (hazard ratio = 1.40; 95% CI: 1.18-1.67; P =.0002); and platelet count (hazard ratio/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 years and 10 years (responders) with positive predictive values of 98% and 88%, respectively. Up to 22% and 21% of events and nonevents, respectively, 10 years after initiation of treatment were correctly reclassified in comparison with earlier proposed criteria. In subgroups of patients aged <45, 45-52, 52-58, 58-66, and ≤66 years, 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 years after treatment. Conclusions We developed and validated scoring system (the GLOBE score) to predict transplant-free survival of ursodeoxycholic acid-treated patients with PBC. This score might be used to select strategies for treatment and care.

Original languageEnglish (US)
Pages (from-to)1804-1812.e4
JournalGastroenterology
Volume149
Issue number7
DOIs
StatePublished - Dec 1 2015

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Keywords

  • Autoimmune Liver Disease
  • Cholestasis
  • Predictive Factor
  • Prognosis

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Lammers, W. J., Hirschfield, G. M., Corpechot, C., Nevens, F., Lindor, K. D., Janssen, H. L. A., Floreani, A., Ponsioen, C. Y., Mayo, M. J., Invernizzi, P., Battezzati, P. M., Parés, A., Burroughs, A. K., Mason, A. L., Kowdley, K. V., Kumagi, T., Harms, M. H., Trivedi, P. J., Poupon, R., ... Van Buuren, H. R. (2015). Development and Validation of a Scoring System to Predict Outcomes of Patients with Primary Biliary Cirrhosis Receiving Ursodeoxycholic Acid Therapy. Gastroenterology, 149(7), 1804-1812.e4. https://doi.org/10.1053/j.gastro.2015.07.061