Validation, clinical utility and limitations of the Amsterdam-Oxford model for primary sclerosing cholangitis

Abstract

Background & aims: Recently the Amsterdam-Oxford model (AOM) was introduced as a prognostic model to assess the risk of death and/or liver transplantation (LT) in primary sclerosing cholangitis (PSC). We aimed to validate and assess the utility of the AOM.

Methods: Clinical and laboratory data were collected from the time of PSC diagnosis until the last visit or time of LT or death. The AOM was calculated at yearly intervals following PSC diagnosis. Discriminatory performance was assessed by calculation of the C-statistic and prediction accuracy by comparing the predicted survival with the observed survival in Kaplan-Meier estimates. A grid search was performed to identify the most discriminatory AOM threshold.

Results: A total of 534 patients with PSC and a mean (SD) age of 39.2 (13.1) years were included. The diagnosis was large duct PSC in 466 (87%), PSC with features of autoimmune hepatitis in 52 (10%) and small-duct PSC in 16 (3%). During the median (IQR) follow-up of 7.8 (4.0-12.6) years, 167 patients underwent LT and 65 died. The median LT-free survival was 13.2 (11.8-14.7) years. The C-statistic of the AOM ranged from 0.67 at baseline to 0.75 at 5 years of follow-up. The difference between the predicted and observed survival ranged from -1.6% at 1 year to + 3.9% at 5 years of follow-up. Patients that developed AOM scores >2.0 were at significant risk of LT or death (time-dependent hazard ratio 4.09; 95% CI 2.99-5.61).

Conclusions: In this large cohort of patients with PSC, the AOM showed an adequate discriminative performance and good prediction accuracy at PSC diagnosis and during follow-up. This study further validates the AOM as a valuable risk stratification tool in PSC and extends its utility.

Lay summary: In our study we assessed whether the Amsterdam-Oxford model (AOM) is able to correctly estimate the risk of liver transplantation or death in patients with primary sclerosing cholangitis (PSC). This model uses 7 objective and readily available variables to estimate prognosis for individual patients at the time of PSC diagnosis. The AOM may aid in patient counselling and timing of diagnostic procedures or therapeutic interventions for complications of liver disease. We confirm that the model works well at PSC diagnosis, but also when the AOM is recalculated at different timepoints during follow-up, greatly improving the applicability of the model in clinical practice and for individual patients.

Keywords: Autoimmune liver disease; Cholestasis; Primary sclerosing cholangitis; Risk stratification, prognostic modelling.