A Prospective, Interventional, Longitudinal APAC Study Evaluating Clinical Utility of GAAD Score for Detection of Hepatocellular Carcinoma in a High-risk APAC Patient Population
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 入组人数
- 2,100
- 试验地点
- 1
- 主要终点
- True Positive Rate (Sensitivity) of Combined Ultrasound + GAAD Score for HCC Surveillance
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Screening
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
GAAD Score
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).
干预措施: GAAD score (Diagnostic Test)
结局指标
主要结局
True Positive Rate (Sensitivity) of Combined Ultrasound + GAAD Score for HCC Surveillance
时间窗: Over 24 months of patient follow-up
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)
False Positive Rate of Combined Ultrasound + AFP for HCC Surveillance
时间窗: Over 24 months of patient follow-up
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)
True Positive Rate (Sensitivity) of Ultrasound, AFP, and GAAD Score as Standalone Surveillance Modalities
时间窗: Over 24 months of patient follow-up
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)
False Positive Rate of Ultrasound, AFP, and GAAD Score as Standalone Surveillance Modalities
时间窗: Over 24 months of patient follow-up
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)
False Positive Rate of Combined Ultrasound + GAAD Score for HCC Surveillance
时间窗: Over 24 months of patient follow-up
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)
True Positive Rate (Sensitivity) of Combined Ultrasound + AFP for HCC Surveillance
时间窗: Over 24 months of patient follow-up
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)
次要结局
- Sensitivity and Specificity of Combined Ultrasound + AFP(Over 24 months of patient follow-up)
- Longitudinal Changes in PIVKA-II Levels Prior to HCC Diagnosis(Over 24 months of patient follow-up)
- 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)
- Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of Combined Ultrasound + AFP(Over 24 months of patient follow-up)
- Longitudinal Changes in AFP Levels Prior to HCC Diagnosis(Over 24 months of patient follow-up)
- Longitudinal Changes in GAAD Score Prior to HCC Diagnosis(Over 24 months of patient follow-up)
- Number of Additional Early-Stage HCCs Detected Using GAAD(Over 24 months of patient follow-up)
- Number of Additional CT or MRI Imaging Procedures Triggered by Surveillance Tests(Over 24 months of patient follow-up)
- Relative False Positive Rate of Additional CT or MRI Imaging Procedures(Over 24 months of patient follow-up)