NCT05541601 - Prospective Cohort for Early Detection of Liver Cancer | Crick

Overview

This study aims to recruit 3000 people with liver cirrhosis into a Prospective cohort for early detection of Liver cancer - the Pearl cohort. The study team believe that using a combination of novel tests may improve the detection of early Hepatocellular Carcinoma (HCC).

During a four-year follow-up period, around 100 Pearl patients are expected to be diagnosed with HCC. Blood, urine, clinical and imaging data will be collected over the follow up period. The samples will be used to identify a range of tests (including genetic, protein and other biomarkers), which along with the clinical data will hopefully identify those most at risk of developing HCC, and to identify HCC at the earliest possible time points.

Study Type

OBSERVATIONAL

Enrollment

3,000

Conditions

Cirrhosis Hepatocellular Carcinoma

Interventions

Blood and Urine samplesOTHER

The samples will be used to identify a range of tests (including genetic, protein and other biomarkers), which along with the clinical data will hopefully identify those most at risk of developing HCC, and to identify HCC at the earliest possible time points.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 100 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Patients of all genders, age \>18 years 2. Participant is willing and able to give informed consent for participation in the study. 3. Evidence of cirrhosis CP A or B (as defined below, cirrhosis ever diagnosed), with an underlying aetiology of at least one of the following: chronic Hepatitis B Virus (HBV) infection, chronic Hepatitis C Virus (HCV) infection, alcoholic liver disease, non-alcoholic fatty liver disease or haemochromatosis Cirrhosis Diagnosis Definition 1. Histological assessment (Ishak stage 5 or 6) or 2. At least one of the following: i. Validated non-invasive marker of fibrosis including fibroscan, AST to Platelet Ratio Index (APRI) score \>2 or Enhanced Liver Fibrosis (ELF) score \>10.48 or Fibrotest score \>0.73. Fibroscan readings should be assessed by aetiology as below: * HBV: \>=10 kPa * HCV: \>=14.5 kPa * Alcoholic Liver Disease (ALD): \>=19.5 kPa * Non-alcoholic fatty liver disease (NAFLD): \>=15 kPa * Haemochromatosis: \>=12kPa ii. Evidence of varices at endoscopy or imaging in the context of a patent portal vein iii. Definitive radiological evidence of cirrhosis (i.e. nodularity of liver and splenomegaly on Ultrasound/CT) Exclusion Criteria: 1. Diagnosis of current OR historical hepatocellular carcinoma 2. Liver transplant recipients or patients on active listing for liver transplantation 3. Child-Pugh C cirrhosis 4. In the view of the clinician, if the patient has a co-morbidity likely to lead to death within the following 12 months 5. In the view of the clinician, if the patient was not thought to be suitable for HCC surveillance

Locations (1)

Hepatology Clinical Trial Unit, John Radcliffe Hospital

Oxford, Oxfordshire, United Kingdom

RECRUITING

Outcomes

Primary Outcomes

Sensitivity of novel diagnostic approaches for the early diagnosis of HCC in enrolled patients who are diagnosed with HCC by conventional approaches.

Diagnostic approaches to be tested will include: 1. detection of epigenetic (e.g. methylation profiling) and genetic mutations, and copy number variations in circulating tumour DNA; 2. multiparametric MRI liver imaging including MR biomarkers of inflammation, fibrosis, fat and iron content; 3. host genetic makeup (relevant variants identified through Genome Wide Association Studies); 4. detection of autoantibodies to tumour associated antigens; 5. epitope mapping of circulating antibody repertoire using random peptide libraries; 6. protein biomarkers including the L3 isoform of alphafetoprotein, and des-gammacarboxy- prothrombin; 7. proteomic and metabolomic profiling, including steroid metabolic signatures in urine.

Time frame: When 50 cases of HCC have accumulated through to study completion; up to 5 years

Specificity of novel diagnostic approaches for the early diagnosis of HCC in enrolled patients who are diagnosed with HCC by conventional approaches.

Diagnostic approaches to be tested will include: 1. detection of epigenetic (e.g. methylation profiling) and genetic mutations, and copy number variations in circulating tumour DNA; 2. multiparametric MRI liver imaging including MR biomarkers of inflammation, fibrosis, fat and iron content; 3. host genetic makeup (relevant variants identified through Genome Wide Association Studies); 4. detection of autoantibodies to tumour associated antigens; 5. epitope mapping of circulating antibody repertoire using random peptide libraries; 6. protein biomarkers including the L3 isoform of alphafetoprotein, and des-gammacarboxy- prothrombin; 7. proteomic and metabolomic profiling, including steroid metabolic signatures in urine.

Time frame: When 50 cases of HCC have accumulated through to study completion; up to 5 years

Positive/Negative predictive values of novel diagnostic approaches for the early diagnosis of HCC in enrolled patients who are diagnosed with HCC by conventional approaches.

Diagnostic approaches to be tested will include: 1. detection of epigenetic (e.g. methylation profiling) and genetic mutations, and copy number variations in circulating tumour DNA; 2. multiparametric MRI liver imaging including MR biomarkers of inflammation, fibrosis, fat and iron content; 3. host genetic makeup (relevant variants identified through Genome Wide Association Studies); 4. detection of autoantibodies to tumour associated antigens; 5. epitope mapping of circulating antibody repertoire using random peptide libraries; 6. protein biomarkers including the L3 isoform of alphafetoprotein, and des-gammacarboxy- prothrombin; 7. proteomic and metabolomic profiling, including steroid metabolic signatures in urine.

Central Contacts

Study Coordinator

CONTACT

deliver-pearl@ndm.ox.ac.uk

Prospective Cohort for Early Detection of Liver Cancer