An observational study in Cirrhosis and Hepatocellular Carcinoma, sponsored by University of Oxford. Recruiting at 1 site in United Kingdom. Open to participants aged 18 Years to 100 Years. Per ClinicalTrials.gov, last updated 2022-09-15.
Sponsored by University of Oxford · Observational
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.
3,182 studies on the registry are indexed under Carcinoma, Hepatocellular; 954 are open to participants now.
This study's planned enrollment of 3,000 is above the median of 200 across 754 observational studies indexed under Carcinoma, Hepatocellular.
Browse Carcinoma, Hepatocellular studies →University of Oxford is the lead sponsor of 794 studies on the registry; 117 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Patients with Child-Pugh (CP) A or B cirrhosis with no current or historical diagnosis of HCC. Diagnosis of cirrhosis can be based on, laboratory, imaging or histology criteria (e.g. the latter including Ishak stage >=5). Participants can be recruited to other interventional studies for treatment of cirrhosis or prevention of HCC prior to or during participation in the Pearl study.
Cirrhosis Diagnosis Definition
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:
Exclusion Criteria:
All 3000 patients recruited to the Pearl study
Other: Blood and Urine samples
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.
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.
Time frame: When 50 cases of HCC have accumulated through to study completion; up to 5 years
To develop models that can be used to "risk-stratify" cirrhosis patients according to their future risk of HCC
The Harrell's Concordance Index (C-index) will be calculated for each biomarker/model of interest. The minimum and maximum C-index scores are 0 and 1, respectively, where the higher the score the better the biomarker/model is at identifying HCC risk. C-index values indicate the degree to which individuals who develop HCC have a higher risk score than those who do not. C-index values will be adapted to incorporate non-HCC mortality as a competing risk. The C-index value will be used to identify the biomarkers/models with the best discriminative ability.
Time frame: Throughout study to completion; 5 years
To better understand the incidence of HCC in a UK population stratified by underlying cirrhosis aetiology
Cumulative incidence of HCC according to cirrhosis aetiology
Time frame: At 1, 3 and 5 year post- baseline.
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