Use of Gender, Age, Alfa-fetoprotein (AFP), and Des-gamma-carboxyprothrombin (PIVKA-II) or GAAD Score in Addition to Ultrasound for Surveillance of People At-risk for Developing Hepatocellular Carcinoma in Asia in Order to Detect Early Liver Cancer

HCC surveillance is currently limited by underutilization and the suboptimal performance of AFP. This prospective, single-arm study investigates whether the GAAD score (Gender, Age, AFP, and PIVKA-II) enhances HCC detection when added to standard-of-care surveillance. High-risk patients will undergo US plus GAAD score testing every six months for two years. The primary analysis compares the relative true positive rate (rTPR) and relative false positive rate (rFPR) of surveillance modalities (US, AFP, GAAD) against combined strategies (US+AFP; US+GAAD), utilizing a 2.57 GAAD cut-off. Secondary endpoints include longitudinal biomarker kinetics, early-stage HCC detection rates, and the impact on downstream imaging (CT/MRI) volume. Ultimately, this study seeks to define the role of GAAD as a surveillance adjunct and inform future clinical guidelines for biomarker-enhanced HCC screening.

This is a prospective, non-randomized, open-label, interventional diagnostic utility study Study procedure Upon enrollment, patients will be followed for 2 years. Surveillance visits will take place at every 6 months intervals according to national guidelines and usual clinical practice. Biomarkers will be assessed using routine blood draw taken at each surveillance visit. Hence, no additional blood draw will be required as per study protocol. Blood collection will be conducted according to local's standard procedures. The following parameters will be assessed at baseline and each follow-up visit. * Characteristics (age, sex, height, weight) * Blood test results (platelets, liver and kidney function, PT, viral infection, liver fibrosis markers) * Fib4 * BMI * Child-Pugh Score * AFP, PIVKA, GAAD * Ultrasound (US): liver evaluation, including existing liver steatosis and its degree if available (according to local clinical practice and used guidelines) * Diabetes type (ICD-10) * Dyslipidemia status * Diagnostic of Hypertension * Central obesity status (defined as waist more than 80 cm - women and 90 cm - male) The Elecsys® AFP, and Elecsys® PIVKA-II will be measured using the Elecsys analyzer, and the GAAD score for each case will be calculated using automatic calculation flow navifyTM Algo Suite. * Elecsys® AFP and Elecsys® PIVKA will be tested and interpreted independent of GAAD as per investigators discretion and/or according to local clinical practice. * GAAD - calculate using navify AlgoSuite In case of positive biomarker/score or imaging, result patients will be subjected further diagnostic workup (recall procedure) with multiphasic contrast-enhanced CT or MRI as described below. Due to its better performance, MRI is the preferred modality but CT can be performed alternatively. Recall procedure For MRI/CT, the following protocols must be applied in order to provide optimal diagnostic performance in accordance with local current clinical practice and Guidelines recommendation (AASLD1, EASL2 and APASL3). The recall procedure with multiphasic contrast-enhanced CT or MRI will be triggered for each patient fulfilling one of the following criteria: * Patients with any suspicious lesion ≥ 1 cm on ultrasound should undergo diagnostic evaluation with multiphasic contrast-enhanced CT or MRI * AFP ≥ 20 ng/ml or rising AFP (on two consecutive tests or doubling of AFP levels) * Patients with limited ultrasound visualization may undergo surveillance contrast-enhanced MRI or multiphase CT based on medical evaluation of treating physician in line with local current clinical practice. For patients with new lesion or lesion \<1 cm lesion on abdominal ultrasound will undergo repeat short-interval evaluation (ultrasound, AFP, PIVKA measurements and GAAD score calculation) in approximately 3-4 months . As part of the study, PIVKA II and GAAD score will be performed and patients with GAAD score ≥ 2.57 will be followed up with multiphasic contrast-enhanced Покажи пълното описание...

Inclusion Criteria: * Signed informed consent form (ICF). * Age above 18 years. * Patients with chronic liver disease who have an indication for HCC surveillance, including: * Liver cirrhosis of any etiology (e.g., chronic HBV, HCV, NASH, alcohol). * Non-cirrhotic chronic liver disease (HCV, MASH, ALD) with evidence of F3 stage fibrosis. * Chronic HBV infection with a clinical diagnosis of non-cirrhosis Exclusion Criteria: * Diagnosis with any cancer other than non-melanoma skin cancer. * Pre-existing diagnosed malignancies, including previous HCC. * Life expectancy of less than 2 years. * Use of Vitamin K antagonists within one week before enrolment. * Women who are pregnant or lactating. * Glomerular filtration rate (GFR) \< 60 mL/min/1.73 m². * Significant hepatic decompensation or a Child-Pugh score of C. * Unwillingness or inability to undergo CT and MRI imaging. * Unwillingness to participate in the study.