A Prospective, Interventional, Longitudinal APAC Study Evaluating Clinical Utility of GAAD Score for Detection of Hepatocellular Carcinoma in a High-risk APAC Patient Population
Phase: NA
Conditions: Hepatecellular Carcinoma, Cirrhosis, HBV Infection
Sponsor: Mahidol University

Official Study Title: 
A Prospective, Interventional, Longitudinal APAC Study Evaluating Clinical Utility of the GAAD 
Score for Detection of Hepatocellular Carcinoma in a High-Risk APAC Patient Population 
 
Study Acronym: 
STOP HCC-GAAD-APAC-Thailand 
 
ClinicalTrials.gov Identifier: 
NCT: Not yet assigned 
 
Document Type: 
Clinical Trial Protocol Synopsis 
 
Document Version: 
Version 1.0 
 
Document Date: 
17 October 2025 
 
Sponsor / Responsible Party: 
Faculty of Medicine Siriraj Hospital 
 
Country / Region: 
Asia-Pacific (Thailand) 
 
 

Study Title 
A Prospective, Interventional, Longitudinal APAC Study Evaluating Clinical Utility of the GAAD 
Score for Detection of Hepatocellular Carcinoma in a High-Risk APAC Patient Population 
 
Acronym 
STOP HCC-GAAD-APAC-Thailand 
 
Brief Summary 
Hepatocellular carcinoma (HCC) surveillance is frequently underutilized, and currently available 
biomarkers, such as alpha-fetoprotein (AFP), demonstrate suboptimal diagnostic performance. 
This prospective study aims to evaluate a simplified multivariate index, the GAAD score—
comprising gender, age, alpha-fetoprotein (AFP), and protein induced by vitamin K absence or 
antagonist-II (PIVKA-II)—for its ability to improve the detection of hepatocellular carcinoma in 
patients with chronic liver disease. 
The study hypothesizes that the addition of the GAAD score to standard surveillance strategies 
will improve diagnostic performance for HCC and may provide evidence to support its inclusion 
in future clinical practice guidelines. 
 
Study Design 
 
Study Type: Interventional (Diagnostic Utility Study) 
 
Study Phase: Not Applicable 
 
Primary Purpose: Diagnostic 
 
Study Model: Single Group Assignment 
 
Allocation: Non-Randomized 
 
Masking: None (Open Label) 
 
Study Start Date: To be determined 
 
Primary Completion Date: 24 months (follow-up period) 
 
Study Completion Date: 36 months (enrollment plus follow-up) 
 
 

Outcome Measures 
Primary Outcome Measures 
Measure: Relative true positive rate and relative false positive rate of surveillance modalities 
Description: 
To evaluate the diagnostic performance of ultrasound, serum AFP, and the GAAD score as 
standalone surveillance tests, as well as the combinations of ultrasound plus AFP and 
ultrasound plus GAAD. The GAAD score cut-off for this endpoint is 2.57. 
Time Frame: Over 24 months of patient follow-up 
 
Secondary (Exploratory) Outcome Measures 
1. Measure: Comparative clinical performance of GAAD 
Description: To compare the clinical performance of the GAAD algorithm with 
ultrasound, AFP, PIVKA-II, and the combination of ultrasound plus AFP, including 
positive predictive value (PPV), negative predictive value (NPV), sensitivity, specificity, 
and area under the receiver operating characteristic curve (AUC), stratified by HCC stage 
and etiology. 
Time Frame: Over 24 months of patient follow-up 
2. Measure: Biomarker kinetics 
Description: To assess longitudinal changes in Elecsys AFP, Elecsys PIVKA-II, and the 
GAAD score leading up to an HCC diagnosis in confirmed cases. 
Time Frame: Over 24 months of patient follow-up 
3. Measure: Additional early-stage HCCs identified 
Description: To quantify the number of additional early-stage hepatocellular carcinoma 
cases identified through use of the GAAD score compared with standard surveillance 
methods. 
Time Frame: Over 24 months of patient follow-up 
4. Measure: Additional imaging procedures triggered 
Description: To count the number of additional computed tomography (CT) or magnetic 
resonance imaging (MRI) procedures triggered by positive GAAD, AFP, or ultrasound 
results and to calculate the relative false positive rate. 
Time Frame: Over 24 months of patient follow-up 
 
Arms and Interventions 
Arm: High-Risk Cohort 

Intervention: Diagnostic Test – GAAD Score 
All enrolled participants will undergo standard hepatocellular carcinoma surveillance consisting 
of blood sampling and abdominal ultrasound every 6 months for 24 months. Blood samples will 
be analyzed for serum AFP and PIVKA-II to calculate the GAAD score. 
A GAAD score of ≥ 2.57 will trigger a recall procedure, defined as further diagnostic evaluation 
using multiphasic contrast-enhanced CT or MRI. This is in addition to standard recall triggers, 
including detection of a suspicious hepatic lesion measuring ≥ 1 cm on ultrasound or elevated 
or rising serum AFP levels (≥ 20 ng/mL). 
 
Eligibility Criteria 
Ages Eligible for Study: ≥ 18 years 
Sexes Eligible for Study: All 
Accepts Healthy Volunteers: No 
Inclusion Criteria: 
 
Signed informed consent form 
 
Age ≥ 18 years 
 
Chronic liver disease with an indication for HCC surveillance, including: 
o Liver cirrhosis of any etiology (e.g., chronic hepatitis B virus, hepatitis C virus, 
metabolic dysfunction–associated steatohepatitis, or alcohol-related liver 
disease) 
o Non-cirrhotic chronic liver disease with evidence of stage F3 fibrosis 
o Chronic hepatitis B virus infection with a clinical diagnosis of non-cirrhotic liver 
disease 
Exclusion Criteria: 
 
Any active malignancy other than non-melanoma skin cancer 
 
History of prior malignancy, including hepatocellular carcinoma 
 
Life expectancy < 2 years 
 
Use of vitamin K antagonists within 1 week prior to enrollment 
 
Pregnancy or breastfeeding 
 
Estimated glomerular filtration rate < 60 mL/min/1.73 m² 

 
Significant hepatic decompensation or Child–Pugh class C liver disease 
 
Unwillingness or inability to undergo CT or MRI 
 
Unwillingness or inability to participate in the study