Standardized CEUS Algorithms for Diagnosis of HCC - Prospective German Multicenter Study

Completed

• Conditions: Hepatocellular Carcinoma; Cholangiocarcinoma, Intrahepatic; Liver Cirrhosis; Liver Cancer; Liver Neoplasms; Liver Diseases
• Interventions: Diagnostic Test: contrast enhanced ultrasound (CEUS); Diagnostic Test: MRI; Diagnostic Test: Histology

• Registration Number: NCT03405909
• Lead Sponsor: University Hospital Erlangen

Brief Summary

Aim of this prospective national multicenter study is to improve standardization of contrast-enhanced ultrasound (CEUS) in the non-invasive diagnosis of hepatocellular carcinoma (HCC) in high-risk patients.

The study is funded by the German Society for Ultrasound in Medicine (DEGUM).

Detailed Description

To date, CEUS criteria for non-invasive diagnosis of HCC include arterial phase hyperenhancement, followed by contrast washout in the portal venous or late phase. We would like to investigate the following points:

1. whether arterial hyperenhancement alone is sufficient for the definite diagnosis of HCC in cirrhosis with CEUS

2. whether a further clearly-defined point of assessment in the late phase after 4-6 minutes is of additional diagnostic value in focal liver lesions showing no contrast washout after 3 minutes

3. diagnostic value of CEUS-based standardised diagnostic algorithms (ESCULAP = Erlanger Synopsis of Contrast Enhanced Ultrasound for Liver lesion Assessment in Patients at risk; CEUS LI-RADS = Contrast Enhanced Ultrasound Liver Imaging Reporting and Data System) for non-invasive diagnosis of HCC in high-risk patients (diagnostic accuracy, interobserver-variability, feasability in clinical Routine).

Study Timeline

• Study First Submitted: 2018-01-12
• Study First Submitted QC: 2018-01-12
• Study First Posted: 2018-01-23
• Study Start: 2018-04-21
• Primary Completion: 2019-04-06
• Study Completion: 2019-04-06
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-28
• Last Update Posted: 2021-03-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 517

Inclusion Criteria

• high risk for HCC
• focal liver lesion on B-mode ultrasound

Exclusion Criteria

• pre-treated HCC lesion
• systemic therapy for HCC (sorafenib, regorafenib and others)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients at risk for HCC	MRI	Patients with any of the following conditions: liver cirrhosis of any origin chronic hepatitis B infection chronic hepatitis C infection with advanced fibrosis non-alcoholic steatohepatitis (NASH) hemochromatosis Interventions: B-mode ultrasound, contrast enhanced ultrasound (CEUS); MRI / histology
Patients at risk for HCC	Histology	Patients with any of the following conditions: liver cirrhosis of any origin chronic hepatitis B infection chronic hepatitis C infection with advanced fibrosis non-alcoholic steatohepatitis (NASH) hemochromatosis Interventions: B-mode ultrasound, contrast enhanced ultrasound (CEUS); MRI / histology
Patients at risk for HCC	contrast enhanced ultrasound (CEUS)	Patients with any of the following conditions: liver cirrhosis of any origin chronic hepatitis B infection chronic hepatitis C infection with advanced fibrosis non-alcoholic steatohepatitis (NASH) hemochromatosis Interventions: B-mode ultrasound, contrast enhanced ultrasound (CEUS); MRI / histology

Primary Outcome Measures

Name	Time	Method
Diagnostic value of standardised CEUS-based algorithms for the non-invasive diagnosis of HCC in high-risk patients	2 years	Diagnostic accuracy, interobserver-variabilty and feasability in clinical routine for CEUS-based algorithms Reference Standard: histology / MRI

Secondary Outcome Measures

Name	Time	Method
Standardisation of CEUS examinations	2 years	Diagnostic value of an additional standardised examination point in the late phase after 4-6 minutes in lesions without contrast washout after 3 minutes Reference Standard: histology / MRI
Diagnostic accuracy of CEUS in intrahepatic cholangiocellular carcinoma (ICC)	2 years	Sensitvity, specificity, positive and negative predictive value of contrast-enhanced ultrasound for non-invasive diagnosis of ICC in high-risk patients / differential diagnosis of HCC versus ICC Reference Standard: histology
Non-inferiority of CEUS versus MRI for non-invasive diagnosis of HCC	2 years	Comparison of CEUS and MRI for non-invasive diagnosis of HCC (diagnostic accuracy, interobserver agreement) Reference Standard: histology
Diagnostic value / dispensability of contrast washout for definite diagnosis of HCC with CEUS	2 years	Sensitvity, specificity, positive and negative predictive value of arterial hyperenhancement only compared with arterial hyperenhancement followed by contrast washout for non-invasive diagnosis of HCC in high-risk patients Reference Standard: histology / MRI
Comparison of two CEUS-based algorithms	2 years	ESCULAP versus CEUS LI-RADS (diagnostic accuracy, interobserver agreement) Reference Standard: histology / MRI
Influence of histological grading on contrast enhancement behaviour	2 years	correlation of histological grading and contrast enhancement pattern

Trial Locations

Locations (1)

University Hospital Erlangen, Department of Medicine 1; 🇩🇪 Erlangen, Bavaria, Germany