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Magnetic resonance imaging (MRI) with magnetic resonance cholangiography (MRC) has become the radiologic standard of reference for diagnosis of primary sclerosing cholangitis (PSC). However, natural history of radiologic features of PSC is poorly known. In the current study, we aimed at analyzing the course of PSC using three-dimensional (3D) MRC and liver MRI to find predictive radiologic features of progression. PSC patients, followed up in our center, with at least two 3D MRCs performed in at least a 1-year interval, were retrospectively reviewed. We built an interpretation standard model to score precisely bile ducts and liver parenchyma features. The primary endpoint was overall radiologic course, including worsening, improvement, or stabilization. Radiologic features were analyzed by logistic regression. We reviewed 289 MRIs from 64 patients upon a mean radiologic follow-up of 4 years (range, 1-9). Radiologic features worsened in 37 patients (58%) and stabilized in 27 (42%); no patient showed improvement. Multivariate analysis resulted in two MRI progression risk scores, based on the combination of predictive radiologic features (score without gadolinium administration = 1 × dilatation of intrahepatic bile ducts + 2 × dysmorphy + 1 × portal hypertension; score with gadolinium administration = 1 × dysmorphy + 1 × parenchymal enhancement heterogeneity). These scores were associated with radiologic progression, with an area under the curve of 80 and 83% ± 4%. Conclusion: A majority of PSC patients develop radiologic aggravation upon MRI over 4 years. Two simple scores can predict radiologic progression.(Hepatology 2014;58:242–250)