Characterization of Methylation Patterns in Hepatocellular Carcinoma

Study Overview
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Brief Summary
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This study is being performed as part of the development process of the Liver EpiCheck test which includes the identification of different methylation profiles in HCC (hepatocellular carcinoma) patients compare to cancer free control in blood samples

Detailed Description
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This is a prospective, multi-center, observational study aimed to collect blood samples and de-identified clinical data from subjects diagnosed with HCC (cases arm) and subjects with high risk for HCC which are undergoing routine surveillance for HCC.

Official Title
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Characterization of Methylation Patterns in Hepatocellular Carcinoma

Conditions
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Hepatocellular Carcinoma, Hepatocellular Cancer, Cirrhosis

Intervention / Treatment
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* Procedure: Blood collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria - Case Group: Age ≥ 22 years Subjects who are willing and able to provide written informed consent Subjects with confirmed diagnosis of HCC, naïve to tumor directed therapy Exclusion Criteria - Case Group: Subjects with current cancer of any kind, other than hepatocellular carcinoma Subjects with a history of cancer of any kind (including hepatocellular carcinoma), other than non-melanoma skin cancer completely resected Coinfection with HIV Prior solid organ transplant Inclusion Criteria - Control Group: Age ≥ 22 years Subjects who are willing and able to provide written informed consent Subjects diagnosed with one of the following: i. Subjects with HCV and cirrhosis ii. Subjects with HBV and cirrhosis iii. Non-cirrhotic chronic HBV subjects at intermediate or high risk of HCC, according to EASL Clinical Practice Guidelines for the management of hepatocellular carcinoma iv. Subjects with Non-Alcoholic Fatty Liver Disease (NAFLD) with cirrhosis. v. Cirrhotic patients due to any other reasons, including alcohol disease Subjects currently undergoing surveillance for hepatocellular carcinoma HCC surveillance imaging (e.g., US, CT, MRI) performed within 3 months prior to baseline visit Subjects with compensated liver function as measured by Child-Pugh Score A or B7 without ascites (all measures should be from the last three months) Exclusion Criteria - Control Group: Subjects with current cancer of any kind, other than hepatocellular carcinoma Subjects with a history of cancer of any kind (including hepatocellular carcinoma), other than non-melanoma skin cancer completely resected Coinfection with HIV Prior solid organ transplant Current substance abuse

Ages Eligible for Study
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Minimum Age: 22 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cases Group<br>Subjects who have already been diagnosed with liver cancer, however did not yet undergo any surgery, ablation, embolization or any other treatment for this cancerous lesion (including, but not limited to systemic therapies) | Procedure: Blood collection<br>* Peripheral blood will be collected via routine venipuncture procedure<br>|
| Control Group<br>Cancer free subjects with high risk to development HCC. High risk subjects include the following: Subjects with HCV (hepatitis C virus) and cirrhosis Subjects with HBV (hepatitis B virus) and cirrhosis Non-cirrhotic chronic HBV subjects at intermediate or high risk of HCC, according to EASL (European Association for the Study of the Liver) Clinical Practice Guidelines for the management of hepatocellular carcinoma Subjects with NAFLD (Non-Alcoholic Fatty Liver Disease) with cirrhosis Cirrhotic patients due to any other reasons, including alcohol disease | Procedure: Blood collection<br>* Peripheral blood will be collected via routine venipuncture procedure<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To collect blood samples and clinical data in order to characterize methylation patterns that will discriminate between HCC and normal hepatic tissue | To collect blood samples and clinical data in order to characterize methylation patterns that will discriminate between HCC and normal hepatic tissue | 60 months | 
| To develop a molecular blood test that will be able to detect HCC based on change in methylation patterns between HCC and normal hepatic tissue | To develop a molecular blood test that will be able to detect HCC based on change in methylation patterns between HCC and normal hepatic tissue | 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver EpiCheck Performance | To assess the performance of the Liver EpiCheck in terms of (1) Sensitivity (2) Specificity (3) NPV(negative predictive value) and (4) PPV (positive predictive value) | 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cirrhosis, Hepatocellular Carcinoma, Methylation, HCC