Validation of Transient Elastography and Comparison with Spleen Length Measurement for Staging of Fibrosis and Clinical Prognosis in Primary Sclerosing Cholangitis

Abstract

BackgroundPatients with primary sclerosing cholangitis (PSC) develop progressive liver fibrosis and end-stage liver disease. Non-invasive and widely available parameters are urgently needed to assess disease stage and the risk of clinical progression. Transient elastography (TE) has been reported to predict fibrosis stage and disease progression. However, these results have not been confirmed in an independent cohort and comparison of TE measurement to other non-invasive means is missing.MethodsIn a retrospective study we collected data from consecutive PSC patients receiving TE measurements from 2006 to 2014 (n = 139). Data from 62 patients who also underwent a liver biopsy were used to assess the performance of TE and spleen length (SL) measurement for the staging of liver fibrosis. Follow-up data from this cohort (n = 130, Hamburg) and another independent cohort (n = 80, Paris) was used to compare TE and SL as predictors of clinical outcome applying Harrel’s C calculations.ResultsTE measurement had a very good performance for the diagnosis and exclusion of higher fibrosis stages (≥F3: AUROC 0.95) and an excellent performance for the diagnosis and exclusion of cirrhosis (F4 vs. < F4: AUROC 0.98). Single-point TE measurement had very similar predictive power for patient outcome as previously published. In a combined cohort of PSC patients (n = 210), SL measurements had a similar performance as TE for the prediction of patient outcome (5 x cross-validated Harrel’s C 0.76 and 0.72 for SL and TE, respectively).ConclusionsBaseline TE measurement has an excellent performance to diagnose higher fibrosis stages in PSC. Baseline measurements of SL and TE have similar usefulness as predictive markers for disease progression in patients with PSC.

Recommendations on the use of magnetic resonance imaging in PSC‐A position statement from the International PSC Study Group

“…TE is an ultrasound shear‐wave–based technology that can also measure liver stiffness. Both have been shown to correlate well with the histological stage of fibrosis and outcomes among patients with PSC . Use of MRE may offer several key advantages when compared to TE.…”

Design and Endpoints for Clinical Trials in Primary Sclerosing Cholangitis

“…These results need prospective validation, which is currently being performed by the international 5‐year prospective FICUS cohort study within the IPSCSG. A recent study from Germany reported findings similar to those of Corpechot et al and demonstrated good performance for diagnosis and exclusion of higher fibrosis stages (≥F3) with an AUROC of 0.95 …”

“…For a cutoff of 120 mm, spleen size measured by ultrasound or on MRI was correlated with patient outcome; PSC patients with a spleen size over 120 mm had a median TFS of only 5.2 years . These researchers recently expanded their series to a combined German/French cohort of 210 PSC patients and found the same adequate Harell's c‐statistics for both TE as for spleen length with regard to its predictive power (liver‐related death, LT, and hepatic decompensation) . However, these data are preliminary and, at this time, are not adequate to support spleen size as a surrogate for clinical trials.…”

“…A recent study from Germany reported findings similar to those of Corpechot et al and demonstrated good performance for diagnosis and exclusion of higher fibrosis stages (≥F3) with an AUROC of 0.95. (58) Baseline data on VCTE from a phase 2 simtuzumab trial were recently presented (ClinicalTrials. gov NCT01672853).…”

Primary Sclerosing Cholangitis Risk Estimate Tool (PREsTo) Predicts Outcomes of the Disease: A Derivation and Validation Study Using Machine Learning

“…To mitigate this, the Enhanced Liver Fibrosis (ELF) Panel was developed and has been shown to predict transplant‐free survival (TFS) . Elastography techniques appear to hold promise to predict clinically relevant events, and prospective validation studies are ongoing . All of these prognostic variables have their own limitations and were examined using traditional statistical methods.…”