STOP HCC-GAAD-APAC-Thailand

NCT07319299 | Enrolling By Invitation

• 1 other identifier: Si 089/2024
• Study Type: interventional
• Target: 2,100
• Locations: 1 country
• Sites: 1

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 incorporation of the GAAD score into standard HCC surveillance strategies will improve diagnostic performance compared with existing surveillance modalities alone and may provide evidence to support its inclusion in future clinical practice guidelines.

Conditions

Hepatecellular Carcinoma; Cirrhosis; HBV Infection

Outcome Measures

Primary Outcomes (6)

• True Positive Rate (Sensitivity) of Ultrasound, AFP, and GAAD Score as Standalone Surveillance Modalities

  To evaluate the true positive rate (sensitivity) of Ultrasound, serum alpha-fetoprotein (AFP), and the GAAD score when used individually for hepatocellular carcinoma (HCC) surveillance. Sensitivity will be calculated for each modality separately by comparing surveillance results with the reference standard diagnosis of HCC. Unit of Measure: Proportion (percentage)

  Over 24 months of patient follow-up

• False Positive Rate of Ultrasound, AFP, and GAAD Score as Standalone Surveillance Modalities

  To evaluate the false positive rate of Ultrasound, serum AFP, and the GAAD score when used individually for HCC surveillance. The false positive rate will be calculated for each modality separately based on surveillance results compared with the reference standard diagnosis. Unit of Measure: Proportion (percentage)

  Over 24 months of patient follow-up

• True Positive Rate (Sensitivity) of Combined Ultrasound + GAAD Score for HCC Surveillance

  To evaluate the true positive rate (sensitivity) of the combined Ultrasound and GAAD score strategy for HCC surveillance. A positive surveillance result will be defined according to the prespecified combination criteria (e.g., either test positive or both tests positive, as defined in the protocol). Unit of Measure: Proportion (percentage)

  Over 24 months of patient follow-up

• False Positive Rate of Combined Ultrasound + GAAD Score for HCC Surveillance

  To evaluate the false positive rate of the combined Ultrasound and GAAD score strategy for HCC surveillance, using the reference standard diagnosis of HCC. Unit of Measure: Proportion (percentage)

  Over 24 months of patient follow-up

• True Positive Rate (Sensitivity) of Combined Ultrasound + AFP for HCC Surveillance

  To evaluate the true positive rate (sensitivity) of the combined Ultrasound and serum AFP strategy for HCC surveillance, based on predefined combination criteria. Unit of Measure: Proportion (percentage)

  Over 24 months of patient follow-up

• False Positive Rate of Combined Ultrasound + AFP for HCC Surveillance

  To evaluate the false positive rate of the combined Ultrasound and serum AFP strategy for HCC surveillance, compared with the reference standard diagnosis of HCC. Unit of Measure: Proportion (percentage)

  Over 24 months of patient follow-up

Secondary Outcomes (12)

• Area Under the Receiver Operating Characteristic Curve (AUC) of GAAD Compared With Ultrasound, AFP, and PIVKA-II

  Over 24 months of patient follow-up

• Sensitivity and Specificity of GAAD Compared With Ultrasound, AFP, and PIVKA-II

  Over 24 months of patient follow-up

• Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of GAAD Compared With Ultrasound, AFP, and PIVKA-II

  Over 24 months of patient follow-up

• Area Under the Receiver Operating Characteristic Curve (AUC) of Combined Ultrasound + AFP

  Over 24 months of patient follow-up

• Sensitivity and Specificity of Combined Ultrasound + AFP

  Over 24 months of patient follow-up

Study Arms (1)

GAAD Score

OTHER

All enrolled participants will undergo standard hepatocellular carcinoma (HCC) surveillance consisting of blood sampling and abdominal ultrasound performed every 6 months for a total follow-up period of 24 months. Blood samples will be analyzed for serum alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) to calculate the GAAD score, a multivariable index incorporating gender, age, AFP, and PIVKA-II. A GAAD score ≥ 2.57 will trigger a recall procedure, defined as diagnostic evaluation with multiphasic contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) of the liver. This recall procedure is conducted in addition to standard surveillance recall criteria, which include detection of a suspicious hepatic lesion measuring ≥ 1 cm on ultrasound or elevated or rising serum AFP levels (≥ 20 ng/mL).

Diagnostic Test: GAAD score

Interventions

GAAD score DIAGNOSTIC_TEST

All enrolled participants will undergo standard hepatocellular carcinoma (HCC) surveillance, consisting of blood sampling and abdominal ultrasound performed every 6 months for a total follow-up period of 24 months. Blood samples will be analyzed for serum alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) to calculate the GAAD score, a multivariable index incorporating gender, age, AFP, and PIVKA-II. A GAAD score of ≥ 2.57 will trigger a recall procedure, defined as further diagnostic evaluation using multiphasic contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) of the liver. This recall procedure is performed in addition to standard surveillance recall criteria, which include detection of a suspicious hepatic lesion measuring ≥ 1 cm on ultrasound or elevated or rising serum AFP levels (≥ 20 ng/mL).

GAAD Score

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults with chronic liver disease who have an indication for hepatocellular carcinoma (HCC) surveillance, including one or more of the following:
• Liver cirrhosis of any etiology (e.g., chronic hepatitis B virus \[HBV\], chronic hepatitis C virus \[HCV\], metabolic dysfunction-associated steatohepatitis \[MASH\], or alcohol-related liver disease \[ALD\])
• Non-cirrhotic chronic liver disease (e.g., HCV, MASH, or ALD) with evidence of stage F3 fibrosis
• Chronic HBV infection with a clinical diagnosis of non-cirrhotic liver disease

You may not qualify if:

• Diagnosis of any active malignancy other than non-melanoma skin cancer
• History of previously diagnosed malignancy, including prior hepatocellular carcinoma
• Life expectancy of less than 2 years
• Use of vitamin K antagonists within 1 week prior to enrollment
• Pregnant or breastfeeding women
• Estimated glomerular filtration rate (GFR) \< 60 mL/min/1.73 m²
• Significant hepatic decompensation or Child-Pugh class C liver disease
• Unwillingness or inability to undergo computed tomography (CT) or magnetic resonance imaging (MRI)
• Unwillingness or inability to provide informed consent or to participate in the study

Sponsors & Collaborators

• Mahidol University: lead

Study Sites (1)

Faculty of Medicine Siriraj Hospital

Bangkoknoi, Bangkok, 10700, Thailand

Location

Related Publications (5)

• Tzartzeva K, Obi J, Rich NE, Parikh ND, Marrero JA, Yopp A, Waljee AK, Singal AG. Surveillance Imaging and Alpha Fetoprotein for Early Detection of Hepatocellular Carcinoma in Patients With Cirrhosis: A Meta-analysis. Gastroenterology. 2018 May;154(6):1706-1718.e1. doi: 10.1053/j.gastro.2018.01.064. Epub 2018 Feb 6.

  PMID: 29425931 RESULT

• Best J, Bechmann LP, Sowa JP, Sydor S, Dechene A, Pflanz K, Bedreli S, Schotten C, Geier A, Berg T, Fischer J, Vogel A, Bantel H, Weinmann A, Schattenberg JM, Huber Y, Wege H, von Felden J, Schulze K, Bettinger D, Thimme R, Sinner F, Schutte K, Weiss KH, Toyoda H, Yasuda S, Kumada T, Berhane S, Wichert M, Heider D, Gerken G, Johnson P, Canbay A. GALAD Score Detects Early Hepatocellular Carcinoma in an International Cohort of Patients With Nonalcoholic Steatohepatitis. Clin Gastroenterol Hepatol. 2020 Mar;18(3):728-735.e4. doi: 10.1016/j.cgh.2019.11.012. Epub 2019 Nov 8.

  PMID: 31712073 RESULT

• Omata M, Cheng AL, Kokudo N, Kudo M, Lee JM, Jia J, Tateishi R, Han KH, Chawla YK, Shiina S, Jafri W, Payawal DA, Ohki T, Ogasawara S, Chen PJ, Lesmana CRA, Lesmana LA, Gani RA, Obi S, Dokmeci AK, Sarin SK. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatol Int. 2017 Jul;11(4):317-370. doi: 10.1007/s12072-017-9799-9. Epub 2017 Jun 15.

  PMID: 28620797 RESULT

• European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol. 2018 Jul;69(1):182-236. doi: 10.1016/j.jhep.2018.03.019. Epub 2018 Apr 5. No abstract available.

  PMID: 29628281 RESULT

• Singal AG, Llovet JM, Yarchoan M, Mehta N, Heimbach JK, Dawson LA, Jou JH, Kulik LM, Agopian VG, Marrero JA, Mendiratta-Lala M, Brown DB, Rilling WS, Goyal L, Wei AC, Taddei TH. AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma. Hepatology. 2023 Dec 1;78(6):1922-1965. doi: 10.1097/HEP.0000000000000466. Epub 2023 May 22. No abstract available.

  PMID: 37199193 RESULT

MeSH Terms

Conditions

Fibrosis

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Tawesak Tanwandee, MD

  Siriraj Hospital

  PRINCIPAL INVESTIGATOR

• Tawesak Tanwandee, MD

  Siriraj Hospital

  STUDY DIRECTOR

• Tawesak Tanwandee, MD

  Siriraj Hospital

  STUDY CHAIR

• Tawesak Tanwandee

  Siriraj Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: GAAD score

Study Record Dates

• First Submitted: November 15, 2025
• First Posted: January 6, 2026
• Study Start: February 2, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: January 6, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

TH (1)