Point Shear Wave Elastography by Acoustic Radiation Force Impulse Quantification in Comparison to Transient Elastography for the Noninvasive Assessment of Liver Fibrosis in Chronic Hepatitis C: A Prospective International Multicenter Study

Abstract

Purpose: The aim of the present prospective European multicenter study was to demonstrate the non-inferiority of point shear wave elastography (pSWE) compared to transient elastography (TE) for the assessment of liver fibrosis in patients with chronic hepatitis C.

Materials and Methods: 241 patients with chronic hepatitis C were prospectively enrolled at 7 European study sites and received pSWE, TE and blood tests. Liver biopsy was performed with histological staging by a central pathologist. In addition, for inclusion of cirrhotic patients, a maximum of 10 % of patients with overt liver cirrhosis confirmed by imaging methods were allowed by protocol (n = 24).

Results: Owing to slower than expected recruitment due to a reduction of liver biopsies, the study was closed after 4 years before the target enrollment of 433 patients with 235 patients in the ‘intention to diagnose’ analysis and 182 patients in the ‘per protocol’ analysis. Therefore, the non-inferiority margin was enhanced to 0.075 but non-inferiority of pSWE could not be proven. However, Paired comparison of the diagnostic accuracy of pSWE and TE revealed no significant difference between the two methods in the ‘intention to diagnose’ and ‘per protocol’ analysis (0.81 vs. 0.85 for F ≥ 2, p = 0.15; 0.88 vs. 0.92 for F ≥ 3, p = 0.11; 0.89 vs. 0.94 for F = 4, p = 0.19). Measurement failure was significantly higher for TE than for pSWE (p = 0.030).

Conclusion: Non-inferiority of pSWE compared to TE could not be shown. However, the diagnostic accuracy of pSWE and TE was comparable for the noninvasive staging of liver fibrosis in patients with chronic hepatitis C.

Zusammenfassung

Ziel: Ziel der vorliegenden prospektiven europäischen Multicenterstudie war es die Nicht-Unterlegenheit der Punkt-Scherwellenelastographie(pSWE) im Vergleich zur transienten Elastographie(TE) für die Beurteilung des Leberfibrosestadiums bei Patienten mit chronischer Hepatitis C nachzuweisen.

Material und Methoden: 241 Patienten mit chronischer Hepatitis C wurden prospektiv an 7 europäischen Zentren eingeschlossen und erhielten eine pSWE, TE und laborchemische Diagnostik. Die Leberhistologie wurde durch einen zentralen Pathologen beurteilt. Zusätzlich wurden maximal 10 % der Patienten ohne Leberhistologie mit gesicherter Leberzirrhose eingeschlossen (n = 24).

Ergebnisse: Bedingt durch einen europaweiten Rückgang der Zahl der Leberbiopsien wurde die Studie nach 4 Jahren Rekrutierung beendet bevor die Ziel-Patientenzahl von 433 erzielt werden konnte. Es konnten 235 Patienten in die ‘intention to diagnose’-Analyse und 182 Patienten in die ‘per protocol’-Analyse eingeschlossen werden. Die statistische Nicht-Unterlegenheitsgrenze wurde angepasst an die geringere Patientienzahl (0,075), die Nicht-Unterlegenheit von pSWE konnte nicht belegt werden. Jedoch ergab der gepaarte Vergleich der diagnostischen Genauigkeit von pSWE und TE keinen signifikanten Unterschied zwischen beiden Methoden sowohl in der ‘intention to diagnose’, als auch in der ‘per protocol’-Analyse (0,81 vs. 0,85 für F ≥ 2, p = 0,15; 0,88 vs. 0,92 für F ≥ 3, p = 0,11; 0,89 vs. 0,94 für F = 4, p = 0,19). Die Rate an Fehlmessungen war mit TE signifikant höher als mit pSWE (p = 0,030).

Schlussfolgerung: Die Nicht-Unterlegenheit von pSWE im Vergleich zu TE konnte nicht nachgewiesen werden. Jedoch war die diagnostische Genauigkeit von pSWE und TE vergleichbar gut für die nicht-invasive Beurteilung des Leberfibrosestadiums.

Clinical Trials Registration: NCT 01113814

Key words

ultrasound - staging - abdomen - hepatic veins

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