Prognostic performance of liver stiffness measurements in primary sclerosing cholangitis: the prospective FICUS cohort.

Abstract

Predicting outcomes of primary sclerosing cholangitis (PSC) by reliable and simple tools is an unmet need. Retrospective studies have suggested that liver stiffness measurement (LSM) by vibration-controlled transient elastography (Fibroscan®) can predict outcomes. We aimed to validate the prognostic value of LSM statics and determine the relevance of LSM dynamics in a large, prospective, cohort study. Clinical, biological and LSM data of adult patients with uncomplicated PSC were prospectively recorded annually for 5 years. LSM was assessed either continuously or according to 3 Baveno-VII classes (<10kPa, >10-<15kPa, >15kPa). The primary endpoint was transplant-free survival. Adjusted hazard ratios (aHRs) and 95% confidence intervals (95%CIs) were determined using time-dependent multivariable Cox regression analyses. Effect of LSM change was evaluated using joint modeling. Progression was defined by a significantly positive individual LSM slope. 538 patients with at least one reliable LSM and follow-up available (median: 60.7 months, Q1-Q3(48.6-66.0)) were analyzed. Median baseline LSM was 7.6(5.8-11.7)kPa. Nineteen patients died and 72 were transplanted. Baseline LSM was strongly and independently linked to the risk of death or transplantation (RDT). For the groups 2.5--<10kPa, 10--<15kPa, >15kPa, 5 years transplant-free survival was 93.9%(90.3-%-96.2%), 78.1%(66.2%-86.3%) and 46.0%(34.6%-56.7%) respectively. Progressors experienced a worst transplant-free survival vs non-progressors: aHR 3.12(1.55-6.24), P=0.001. Each one kPa/year increment was associated with 18% increase in RDT. This observational study validates the strong prognostic value of both static and dynamic LSM in PSC, as assessed by Fibroscan®. These results support the use of LSM as a risk stratification tool and potential surrogate endpoint in clinical trials.