An interventional study of PIVKA-II and GAAD score calculation in Liver Cirrhosis, Hepatitis B, Chronic and Hepatitis C, Chronic, sponsored by Siriraj Hospital. Enrolling by invitation at 1 site in Thailand. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-04-24.
Sponsored by Siriraj Hospital · Not applicable, Interventional, and Screening
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.
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:
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 CT or MRI as recall procedure.
Clinical decisions will be based on local radiologic assessment. Based on multiphasic contrast-enhanced CT or MRI - the diagnosis of HCC will be made in line with current clinical practice:
For patients with positive findings in any surveillance modality (refers to US, AFP or GAAD; if PIVKA-II alone is above MDP cut-off, this will not be considered a positive case), the following additional parameters will be documented upon diagnostic workup:
Right to withdraw Subjects have the right to withdraw from the study at any time for any reason. If lost to follow-up, the assigned study staff will try to contact the subject by telephone followed by registered mail to establish and document as completely as possible the reason for the withdrawal.
Subjects will be allowed to miss one scheduled visit. Subjects with >1 missed visits will be excluded from further follow-up.
Subjects will be informed of circumstances under which their participation may be terminated by the responsible investigator without the subject's consent. The investigator may withdraw subjects from the study in the event of intercurrent illness, adverse events, lack of compliance with the study and/or study procedures (e.g., study visits), or any reason where it is felt that it is in the best interest of the subject to be terminated from the study. Any administrative or other reasons for withdrawal will be documented and explained to the subject. If the reason for removal of a subject from the study is an Adverse Event, the principal specific event will be recorded in the medical record.
5. Statistics Primary and secondary endpoint(s) Primary endpoint
Exploratory Clinical performance of Elecsys® AFP, Elecsys® PIVKA-II, GAAD -score for the aid in diagnosis of early and all stages stage Hepatocellular Carcinoma (HCC).
Exploratory endpoint
Statistical methods Primary endpoints:
● Exploratory Clinical performance of Elecsys® AFP, Elecsys® PIVKA-II, GAAD -score for the aid in diagnosis of early and all stages stage Hepatocellular Carcinoma (HCC). - descriptive (PPV, NPV, Sens, Spec AUC/ROC)
Exploratory endpoints,
Sample size, level of significance, and power Sample size estimation:
As HCC has a low annual prevalence (consider 1.5% \& 2% for now), the precision of the sensitivity estimate (i.e., width of the 95% confidence interval) is the main prerequisite for the sample size, as sensitivity is calculated from HCC cases. Assuming a decent target of 20% sensitivity 95% confidence interval width, a true sensitivity of 86.5% (MCE study), and a prevalence of 1.5% \& 2% over two years follow-up, a sample size of 2100 samples would be required to achieve a 95% confidence interval width of 19% (1.5% annual prevalence) and 16% (2% annual prevalence) respectively, which is considered sufficient.
1,298 studies on the registry are indexed under Liver Cirrhosis; 338 are open to participants now.
This study's planned enrollment of 2,100 is above the median of 78 across 739 interventional studies indexed under Liver Cirrhosis.
Browse Liver Cirrhosis studies →Siriraj Hospital is the lead sponsor of 95 studies on the registry; 32 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Patients with chronic liver disease who have an indication for HCC surveillance, including:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Child-Pugh class
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Addition of PIVKA-II and GAAD score will probably detect more HCC and compare with ultrasound alone or ultrasound plus AFP
Diagnostic Test: PIVKA-II and GAAD score calculation
Measurement of PIVKA-II to routine ultrasound and AFP and calculation of GAAD score
Occurrence of hepatocellular carcinoma (HCC)
New HCC detected by imaging or pathology
Time frame: 24 months of follow up
Relative True Positive Rate of Surveillance Modalities
Time frame: 24 months
Relative False Positive Rate of Surveillance Modalities
Time frame: 24 months
Plan to share: No
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