Development and Validation of a Scoring System to Predict Outcomes of Patients With Primary Biliary Cirrhosis Receiving Ursodeoxycholic Acid Therapy.
OBJECTIVE
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.
Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Willem J
WJ
Lammers
NIHR Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, United Kingdom.
Gideon M
GM
Hirschfield
Centre de Référence des Maladies Inflammatoires des Voies Biliaires, Hôpital Saint-Antoine, APHP, Paris, France.
Christophe
C
Corpechot
Department of Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
Frederik
F
Nevens
Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota; Arizona State University, College of Health Solutions, Phoenix, Arizona.
Keith D
KD
Lindor
Liver Clinic, Toronto Western and General Hospital, University Health Network, Toronto, Ontario, Canada.
Harry L A
HL
Janssen
Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.
Annarosa
A
Floreani
Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
Cyriel Y
CY
Ponsioen
Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas.
Marlyn J
MJ
Mayo
Liver Unit and Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center, Rozzano, Italy.
Pietro
P
Invernizzi
Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.
Pier M
PM
Battezzati
Liver Unit, Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain.
Albert
A
Parés
The Sheila Sherlock Liver Centre, The Royal Free Hospital, London, United Kingdom.
Andrew K
AK
Burroughs
Divison of Gastroenterology and Hepatology, University of Alberta, Edmonton, Alberta, Canada.
Andrew L
AL
Mason
Liver Care Network and Organ Care Research, Swedish Medical Center, Seattle, Washington.
Kris V
KV
Kowdley
Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan.
Teru
T
Kumagi
Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Maren H
MH
Harms
NIHR Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, United Kingdom.
Palak J
PJ
Trivedi
Centre de Référence des Maladies Inflammatoires des Voies Biliaires, Hôpital Saint-Antoine, APHP, Paris, France.
Raoul
R
Poupon
Liver Clinic, Toronto Western and General Hospital, University Health Network, Toronto, Ontario, Canada.
Angela
A
Cheung
Liver Unit and Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center, Rozzano, Italy.
Ana
A
Lleo
Liver Unit, Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain.
Llorenç
L
Caballeria
Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Bettina E
BE
Hansen
Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands. Electronic address: h.vanbuuren@erasmusmc.nl.
Henk R
HR
van Buuren
D000328:Adult; D000367:Age Factors; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D003661:Decision Support Techniques; D018450:Disease Progression; D018572:Disease-Free Survival; D005060:Europe; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009656:North America; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D013997:Time Factors; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
D015415:Biomarkers; D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid
Autoimmune Liver Disease; Cholestasis; Predictive Factor; Prognosis