Improving Hepatocellular Carcinoma Screening

Study Overview
=================
Brief Summary
-----------------
This is a monocentric, single blind, interventional, single arm study. It is designed to compare the rates of detection of hepatocellular carcinoma (HCC) by ultrasound (US) used in clinical routine vs. abbreviated magnetic resonance imaging (AMRI). The hypothesis is that dynamic AMRI with extracellular contrast agent injection has a higher patient-level detection rate of HCC than screening US and non-contrast AMRI. Interested and eligible patients will be enrolled and undergo HCC screening rounds including US +/- contrast-enhanced US (clinical routine) and screening MRI within the same week bi-annually.

Official Title
-----------------
Prospective Comparison of Diagnostic Performance and Cost-effectiveness of US and Abbreviated MRI for Hepatocellular Carcinoma Screening

Conditions
-----------------
Screening, Magnetic Resonance Imaging, Hepatocellular Carcinoma, Contrast-enhanced US

Intervention / Treatment
-----------------
* Device: MRI


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All adult patients with chronic liver disease and indication for HCC screening according to the European Association for the Study of the Liver recommendations. Informed Consent signed by the subject Exclusion Criteria: History of HCC History of other malignancy Prior liver nodule categorized as LI-RAD 4, 5 or M History of liver transplantation Pregnancy MRI or MRI contrast agent precaution Any other condition making the patient unsuitable for the study Patient's refusal of transmission of relevant medical conditions found on the medical examinations performed during the study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Screening
Intervention Model: Single Group Assignment
Interventional Model Description: single center interventional prospective study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HCC screening population according to European Association for the Study of the Liver recommendation<br> | Device: MRI<br>* To compare the diagnostic performance of US+/- Constrast-enhanced US and AMRI for HCC detection in an at-risk population<br>* Other names: Constrast-enhanced US;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the diagnostic performance of US+/- CEUS and AMRI for HCC detection in an at-risk population | The patients will undergo all the normal follow-up according to clinical recommendations, consisting of a bi-annual clinical visit in the gastro-enterology department and an US. The US will be followed by CEUS in case of suspicious lesion. On the same week, the study participants will undertake MRI. The data of the full MRI will be used to reconstruct two different AMRI sets for reading: non-contrast (NC-) and dynamic (Dyn-) AMRI. The endpoint is the rate of HCC detection. Outcome measures will be compared in terms of ROC curve and AUC. | Through study completion, an average of 1 year. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the patient-level accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of US +/- CEUS vs. AMRI for HCC. | Diagnostic performance of the different tests [(1)US alone, (2) US + CEUS, (3) NC-AMRI, (4) Dyn-AMRI] will be compared using all patient information (including complete MRI and pathology) as the reference standard. Outcome measures will be compared in terms accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) | Through study completion, an average of 1 year. | 
| Evaluate patient satisfaction and comfort with US +/- CEUS vs. AMRI with a questionnaire | In order to evaluation patient's opinion a survey regarding patient experience and opinion to the different test will be performed. Outcome will be measured in term of level of confort using a 5-scale score: from low discomfort to high discomfort: No discomfort Low discomfort Neutral Comfort high comfort | Once, after the first screening round (US+/-CEUS and MRI), 6 months | 
| To develop and test a DL model for HCC detection based on AMRI. | AMRI DL based model will be analysed in terms of (1) diagnostic performance (ROC, AUC, sensitivitiy, specificity, accuracy) and (2) time savings compared to AMRI read by a radiologist. | Through study completion, an average of 1 year. | 
| To perform a cost-effectiveness analysis comparing US to different alternative screening strategies for HCC in Switzerland. | Cost effectiveness analysis will be perfomed by building a model using all study data: patient characteristics, exam diagnostic performance and patient management costs. Outcome will be analysed in terms of Lifetime costs, quality adjusted life expectancy | Through study completion, an average of 1 year. | 
| To perform a cost-effectiveness analysis comparing US to different alternative screening strategies for HCC in Switzerland. | Cost effectiveness analysis will be perfomed by building a model using all study data: patient characteristics, exam diagnostic performance and patient management costs. Outcome will be analysed in terms of incremental costs effectiveness ratios. | Through study completion, an average of 1 year. |