Real-world Elecsys® GAAD Implementation and Validation to Improve Surveillance and Early Detection of HCC (REVISE-HCC)

Real-world Elecsys® GAAD Algorithm Implementation and Validation to Improve Surveillance and Early Detection of Hepatocellular Carcinoma

Patients with liver cirrhosis are at high risk of developing hepatocellular carcinoma (HCC) which implies significant mortality. At present current surveillance methods detect hepatocellular carcinomas at a late stage resulting in few treatment options for patients and, in the majority of cases, premature death.

The goal of this study is to implement Elecsys® GAAD in real-world hepatocellular carcinoma surveillance for those with liver cirrhosis.

The main questions it aims to answer are:

• Does the introduction of the Elecsys® GAAD algorithm to the surveillance pathway increase early detection of HCC?
• Does the introduction of the Elecsys® GAAD algorithm to the surveillance pathway reduce false positive tests and unnecessary confirmatory investigations?
• Does the new surveillance pathway improve adherence?

Researchers will compare Elecsys® GAAD with standard of care tests to see if it results in earlier detection of hepatocellular carcinoma and will explore potential improvements to the surveillance pathway.

Study Overview

• Status: Recruiting
• Conditions: Liver Cirrhosis; Hepatocellular Carcinoma
• Intervention / Treatment: Diagnostic test: Elecsys® GAAD

• Study Type: Interventional
• Enrollment (Estimated): 600
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Varinder Athwal, PhD; Phone Number: 0300 3309444; Email: varinder.athwal@mft.nhs.uk
• Study Contact Backup: Name: Christopher Mysko, MClinEd MRCP; Phone Number: 0300 3309444; Email: christopher.mysko@mft.nhs.uk

Study Locations

• United Kingdom
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M13 9WL
      • Recruiting
      • Manchester University NHS Foundation Trust
      • Contact: Christopher Mysko, MClinEd MRCP; Phone Number: 07848471145; Email: christopher.mysko@mft.nhs.uk
      • Principal Investigator: Varinder Athwal, MRCP PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with known liver cirrhosis referred into or already under hepatocellular carcinoma surveillance

Exclusion Criteria:

• Pregnancy/breast-feeding.
• Patients who do not have liver cirrhosis
• Patients who already have hepatocellular carcinoma
• Any patient who is unable to understand, retain and weigh information to make an informed decision, will be excluded from the study. The investigators will use every opportunity, including tele-interpretation services to minimise this from happening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Patients with liver cirrhosis eligible for HCC Surveillance; Real-world HCC surveillance cohort will be exposed to Elecsys® GAAD in parallel with standard of care tests.

Diagnostic test: Elecsys® GAAD; Elecsys® GAAD is a CE marked in vitro diagnostic (IVD) multivariate index assay, intended as an aid in the diagnosis of early-stage HCC. It provides a semi quantitative result by combining in an algorithm the quantitative measurements of Elecsys® AFP (alpha-fetoprotein) and Elecsys® PIVKA-II (protein induced by vitamin K absence II) levels in serum and plasma, with gender and age. Clinical evidence showed that Elecsys® GAAD had high performance in detecting HCC (sensitivity 86.5%), particularly early stage (sensitivity 78.9%), with 91.4% specificity for both early and all stages, out-performing current standard of care (Chan et al. 2021). Elecsys® GAAD may be integrated into current surveillance practice to increase early-stage HCC detection rate, reduce unnecessary onward investigations and patient anxiety.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of hepatocellular carcinoma diagnosis	Incidence recorded as number of cases per study cohort	2 years
Stage of hepatocellular carcinoma at diagnosis	Barcelona Clinic Liver Cancer (BCLC) stage 0-D	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rates of false positives for each combination of diagnostic tests	Count (%) of True/False positives for each test (against magnetic resonance imaging (MRI) / computerised tomography (CT)) will be reported. Results from different tests (and their (meaningful) combination) will be tabulated against each other: Alpha-fetoprotein (AFP) vs GAAD; Ultrasound scan (USS) vs GAAD; AFP+ USS vs GAAD; AFP+USS vs GAAD +USS; AFP/GAAD/USS/AFP+USS/GAAD+USS vs MRI/CT for those who proceed to confirmatory imaging.	2 years
Rates of curative treatment	Rates of curative treatment being offered (%) will be recorded on an intention to treat (ITT) basis from Multi-Disciplinary Team (MDT) meeting outcomes.	2 years
Rates of adherence	• Attendance rates for biannual surveillance appointments (%), within predefined tolerance of 5-9 months post previous appointment.	2 years
Rates of discontinuation	• Count (%) of surveillance discontinuation, defined as no visit >12 months.	2 years
Survival rates	Long-term follow up data will be collected to determine rates of survival following HCC diagnosis at 1-year, 3-years and 5-years.	7 years

Collaborators and Investigators

• Sponsor: Manchester University NHS Foundation Trust
• Collaborators: Roche Pharma AG; Imperial College London; University of Manchester; Unity Insights
• Investigators: Principal Investigator: Varinder Athwal, MRCP PhD, Manchester University NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2024
• Primary Completion (Estimated): July 31, 2030
• Study Completion (Estimated): July 31, 2030

Study Registration Dates

• First Submitted: May 24, 2023
• First Submitted That Met QC Criteria: July 24, 2023
• First Posted (Actual): August 2, 2023

Study Record Updates

• Last Update Posted (Estimated): September 24, 2025
• Last Update Submitted That Met QC Criteria: September 23, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: hepatocellular carcinoma; cirrhosis; surveillance; health inequalities; GAAD
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Pathological Conditions, Signs and Symptoms; Carcinoma, Hepatocellular; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: B01938

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No