International Study of High-Risk Patients for Hepatocellular Carcinoma Using Liquid Biopsy

Recruiting

• Conditions: Liver Cancer; Liver Cirrhosis; Hepatocellular Carcinoma; Early Stage Liver Cancer

• Registration Number: NCT05342350
• Lead Sponsor: Johns Hopkins University

Brief Summary

This study has two purposes. One is to conduct a phase IV biomarker validation study in which the investigators will prospectively survey a cohort of patients at risk for liver cancer using semi-annual abdominal ultrasound and GALAD Score for 5 years. The GALAD score is a serum biomarker-based panel that can aid in early detection among patients with a high risk for liver cancer. One is to establish a bio-repository of longitudinally collected bio-specimens from patients with fibrosis/cirrhosis as a reference set for future research.

Detailed Description

Vietnam and Saudi Arabia have some of the highest disease burdens of liver cancer globally. Early detection in asymptomatic patients who are at risk for liver is a strategy to improve survival outcomes in liver cancer management. GALAD score (gender, age, alpha-feto protein (AFP)-L%, AFP and DCP) is a serum biomarker-based panel that can improve HCC early detection in patients with liver fibrosis and cirrhosis. In case-control studies and studies with the design of prospective specimen collection, and retrospective blinded evaluation, GALAD has demonstrated promising clinical utility. However, in order to ascertain its potential role in the surveillance of liver cancer early detection, GALAD needs to be validated prospectively for clinical surveillance of liver cancer (i.e. phase IV biomarker validation study). Thus, the investigators propose to conduct a phase IV biomarker validation study to prospectively survey a cohort of patients at risk for HCC (i.e. patients with compensated cirrhosis and irrespective of cirrhosis etiologies), using semi-annual abdominal ultrasound and GALAD Score for 5 years. In doing so, the investigators aim to validate the potential role of GALAD Score for clinical surveillance and early detection of HCC in Vietnam and Saudi Arabia. Additionally, the investigators will collect and archive biospecimens to develop a bio-repository for liver disease. The biorepository will encourage the sharing of biospecimens and collaboration among physicians or physician-researchers between the US, Vietnam, and Saudi Arabia.

Study Timeline

• Study Start: 2022-04-15
• Study First Submitted: 2022-04-16
• Study First Submitted QC: 2022-04-16
• Study First Posted: 2022-04-22
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-14
• Last Update Posted: 2025-01-16
• Primary Completion: 2027-07-01
• Study Completion: 2027-07-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1600

Inclusion Criteria

1. Provision of signed and dated informed consent form
2. Stated willingness to comply with all study procedures and availability for the duration of the study and up to 5 years post-study follow up
3. Adults aged 18 or older
4. Both genders and all ethnicities
5. Willingness to give written, informed consent to be enrolled into the database
6. Collection of biosamples (serum, plasma, and urine) at each of the 6 months follow up during the study duration
7. Individuals already confirmed to have cirrhosis with MELD ≤ 15 from any etiology (chronic HBV, chronic HCV, NASH cirrhosis, etc.)
8. For chronic HBV and/or /HCV carrier, with or without on treatment
9. Reside in Vietnam or Saudi Arabia at the time of study and provides contact information (email and/or cell phone number for texting)
10. No prior or current treatment of HCC
11. No cancer history within 5 years
12. No participation in a trial for HCC Treatment
13. No prior solid organ transplant
14. Albumin, Bilirubin, Creatinine and INR labs within past 30 days
15. Imaging showing no HCC within 180 days
16. Diagnosis of fibrosis and cirrhosis based on: histology, image showing cirrhotic liver with splenomegaly and platelets <120 mm3, or esophageal or gastric varices on endoscopy AND presence of chronic liver disease/Fibroscan/Fib-4/APRI/ARFI. For viral hepatitis, kPa>=9kPa, APRI >=1; for NAFLD/NASH (FIB-4 > 1.3 & TE > 8kPa)
17. No significant hepatic decompensation
18. No hepatorenal syndrome
19. AFP labs within 180 days irrespective of AFP titer
20. Two phone numbers and personal identification numbers (CMND number)
21. No known AIDS related diseases
22. No significant co-morbid conditions with life expectancy <5 years
23. No other cancer(s)

Exclusion Criteria

1. Decompensated cirrhosis (variceal bleeding, hepatic encephalopathy, ascites, spontaneous bacterial peritonitis, and/or hepatorenal syndrome) or MELD>15
2. Individuals who already have HCC, with or without HCC treatment
3. On liver transplantation list or anticipated to be on the liver transplantation list during the study duration
4. Individuals who cannot, do not want to, or refused to sign the informed consent form (ICF)
5. Any serious or active medical or psychiatric illness, which, in the opinion of the investigator, would interfere with patient treatment, assessment or compliance with the protocol
6. Documentation was not adequate
7. Taking Vitamin K within 7 days prior to clinic follow or having disease affecting Vitamin K levels.
8. Known HIV positive
9. Active drug use or dependence that, in the opinion of the study investigator, would interfere with adherence to study requirements

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
GALAD performance for liver cancer early detection	5 years	Performance of GALAD score determined in association with liver cancer detection by LiRADS criteria in a cohort with compensated cirrhosis undergoing prospective surveillance every 6 months for 5 years.

Secondary Outcome Measures

Name	Time	Method
Establishment of a bio-repository of longitudinally collected from patients with cirrhosis to be used for future studies	5 years	Proportion of study participants agrees to consent for bio-specimen when invited

Trial Locations

Locations (10)

National Guard Hospital in Riyadh; 🇸🇦 Riyadh, Saudi Arabia

Binh An Hospital; 🇻🇳 Rach Gia, Kien Giang, Vietnam

King Saud University Medical Center; 🇸🇦 Riyadh, Saudi Arabia

Institute of Gastroenterology and Hepatology; 🇻🇳 Ha Noi, Vietnam

Dong Da Hospital; 🇻🇳 Ha Noi, Vietnam

Medic Ca Mau; 🇻🇳 Ca Mau, Vietnam

King Faisal Specialist Hospital and Research Centre in Riyadh; 🇸🇦 Riyadh, Saudi Arabia

King Faisal Specialist Hospital and Research Center in Jeddah; 🇸🇦 Jeddah, Saudi Arabia

National Guard Hospital in Jeddah; 🇸🇦 Jeddah, Saudi Arabia

Medic Medical Center-Ho Chi Minh City; 🇻🇳 Ho Chi Minh City, Vietnam