Willem J Lammers1, Gideon M Hirschfield2, Christophe Corpechot3, Frederik Nevens4, Keith D Lindor5, Harry L A Janssen6, Annarosa Floreani7, Cyriel Y Ponsioen8, Marlyn J Mayo9, Pietro Invernizzi10, Pier M Battezzati11, Albert Parés12, Andrew K Burroughs13, Andrew L Mason14, Kris V Kowdley15, Teru Kumagi16, Maren H Harms1, Palak J Trivedi2, Raoul Poupon3, Angela Cheung6, Ana Lleo10, Llorenç Caballeria12, Bettina E Hansen1, Henk R van Buuren17. 1. Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands. 2. NIHR Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, United Kingdom. 3. Centre de Référence des Maladies Inflammatoires des Voies Biliaires, Hôpital Saint-Antoine, APHP, Paris, France. 4. Department of Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium. 5. Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota; Arizona State University, College of Health Solutions, Phoenix, Arizona. 6. Liver Clinic, Toronto Western and General Hospital, University Health Network, Toronto, Ontario, Canada. 7. Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy. 8. Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands. 9. Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas. 10. Liver Unit and Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center, Rozzano, Italy. 11. Department of Health Sciences, Università degli Studi di Milano, Milan, Italy. 12. Liver Unit, Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain. 13. The Sheila Sherlock Liver Centre, The Royal Free Hospital, London, United Kingdom. 14. Divison of Gastroenterology and Hepatology, University of Alberta, Edmonton, Alberta, Canada. 15. Liver Care Network and Organ Care Research, Swedish Medical Center, Seattle, Washington. 16. Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan. 17. Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands. Electronic address: h.vanbuuren@erasmusmc.nl.
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.
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.
Authors: George Cholankeril; Humberto C Gonzalez; Sanjaya K Satapathy; Stevan A Gonzalez; Menghan Hu; Mohammad Ali Khan; Eric R Yoo; Andrew A Li; Donghee Kim; Satheesh Nair; Robert J Wong; Paul Y Kwo; Stephen A Harrison; Zobair M Younossi; Keith D Lindor; Aijaz Ahmed Journal: Clin Gastroenterol Hepatol Date: 2018-02-08 Impact factor: 11.382
Authors: Patrick S C Leung; Jinjung Choi; Guoxiang Yang; Elena Woo; Thomas P Kenny; M Eric Gershwin Journal: Expert Rev Mol Diagn Date: 2016-03-30 Impact factor: 5.225