STOP HCC-GAAD-APAC-Thailand

Mahidol University

Status: Invitation-only

Conditions: Cirrhosis; HBV Infection; Hepatecellular Carcinoma

Treatments: Diagnostic Test: GAAD score

Study type: Interventional

Funder types: Other

Identifiers

NCT07319299

Si 089/2024

Details and patient eligibility

About

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.

Full description

Surveillance and early detection of hepatocellular carcinoma (HCC) increase the likelihood of potentially curative treatment. However, HCC surveillance remains substantially underutilized, even in countries with adequate healthcare resources. Early-stage HCC can be treated with curative intent using local ablation, surgical resection, or liver transplantation.

The role of serum alpha-fetoprotein (AFP) in HCC surveillance varies across international guidelines. AFP is recommended for surveillance by the Asian Pacific Association for the Study of the Liver (APASL), considered optional by the American Association for the Study of Liver Diseases (AASLD), and not recommended by the European Association for the Study of the Liver (EASL). Similar considerations have informed recommendations for combined use of AFP with ultrasound (US) in HCC surveillance by the World Health Organization (WHO) Guidelines for the Prevention, Care and Treatment of Viral Hepatitis (references 1-4).

AFP has demonstrated suboptimal performance as a serologic surveillance marker for HCC. Serum AFP levels may fluctuate in patients with cirrhosis due to hepatitis B virus (HBV) or hepatitis C virus (HCV) activity, exacerbations of underlying liver disease, or the development of HCC, thereby limiting its diagnostic accuracy.

Recently, the GALAD score-a multivariable model incorporating gender, age, AFP-L3, AFP, and protein induced by vitamin K absence or antagonist-II (PIVKA-II)-has been proposed as an alternative approach to improve HCC detection and has demonstrated strong diagnostic performance in patients with cirrhotic HCC. A simplified version of this model, the GAAD score (Roche Diagnostics International Ltd., Rotkreuz, Switzerland), which includes gender, age, AFP, and PIVKA-II, has been shown to achieve comparable diagnostic performance in preliminary analyses (Piratvisuth et al., 2023, submitted).

However, the existing evidence supporting the use of the GALAD and GAAD scores is primarily derived from retrospective and/or case-control studies. Prospective validation in real-world surveillance settings remains limited. This study is therefore designed to prospectively evaluate the diagnostic performance of the GAAD score, alone and in combination with standard surveillance modalities, in patients with chronic liver disease undergoing routine HCC surveillance.

Enrollment: 2,100 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Screening

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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2,100 participants in 1 patient group

GAAD Score

Other group

Description:

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).

Treatment:

Diagnostic Test: GAAD score