Table 3.
Ongoing clinical trials evaluating risk stratification and early detection biomarkers for HCC.
| Biomarker type | Type of test/biomarker | Trial name | Test/biomarker | Target population | Biomarker development phase | Planned no. subjects | Country | Anticipated completion year | NCT No. |
|---|---|---|---|---|---|---|---|---|---|
| Risk stratification | Imaging, clinical test/feature | STARHE | Deep learning of clinical, biological, elastography/ultrasound features | Advanced fibrosis/cirrhosis on HCC screening | 1-3 | 400 | France | 2023 | NCT04802954 |
| SNP | n.a. | MMP1-1607 1G/2G (rs1799750) | Egyptian HCV cirrhosis | 1/2 | 200 | Egypt | 2022 | NCT03722628 | |
| Risk stratification/early detection | Circulating biomarker, microbiome, imaging | ELEGANCE | miRNA panel (early detection), microbiome/MRI/urine, plasma metabolome (risk prediction) | Chronic liver disease from HBV, HCV, or NAFLD | 1-3 | 2,000 | Singapore | 2025 | NCT04965259 |
| Early detection | Circulating biomarker | n.a. | Serum visfatin, vaspin | HCV-related HCC, cirrhosis, healthy controls | 1/2 | 100 | Egypt | 2022 | NCT04763707 |
| Circulating biomarker, clinical test/feature | n.a. | Glycotest HCC panel | HCC, cirrhosis | 2 | 766 | U.S. | 2022 | NCT03878550 | |
| Circulating biomarker | n.a. | lncRNAs-WRAP53, UCA1 | HCC, cirrhosis, and healty controls | 1/2 | 80 | Egypt | 2022 | NCT05088811 | |
| Circulating biomarker, clinical test/feature | ALTUS | mt-HBT, Oncoguard Liver (Multi-target HCC blood test) | Cirrhosis, HBV carriers | 4 | 3,000 | U.S. | 2025 | NCT05064553 | |
| Circulating biomarker, clinical test/feature | LIVER-1 | HelioLiver Test | HCC, controls undergoing routine imaging surveillance for HCC | 4 | 1,200 | U.S. | 2024 | NCT05199259 | |
| Circulating biomarker, clinical test/feature | HEPATIC | HelioLiver Test | HCC, cirrhosis, and HD controls | 2 | 1,000 | China | 2022 | NCT05053412 | |
| Circulating biomarker | SEPT9-CROSS | Epi proColon 2.0 CE (Plasma mSEPT9) | HCC cases and cirrhosis controls | 2 | 530 | France | 2023 | NCT03311152 | |
| Circulating biomarker | n.a. | ctDNA methylation and fragmentation markers, miRNA7, CTC | Esophageal cancer, gastric cancer, colorectal cancer, HCC, healthy controls, pre-cancer | 1-3 | 2,430 | China | 2022 | NCT05431621 | |
| Imaging | FASTRAK | non-contrast AMRI | Compensated cirrhosis | 4 | 944 | France | 2027 | NCT05095714 | |
| Imaging | n.a. | Low-contrast dose CT and deep learning-based reconstruction | Patients undergoing CT for HCC diagnosis or surveillance | 1-3 | 90 | Korea | 2022 | NCT04027556 | |
| Imaging | n.a. | Gadolinium-enhanced AMRI | Cirrhosis | 4 | 150 | U.S. | 2023 | NCT04288323 | |
| Imaging | n.a. | non-contrast AMRI, MRI | Cirrhosis AND reduced visualisation on ultrasound | 4 | 476 | Australia, New Zealand | 2027 | NCT04455932 | |
| Imaging | n.a. | CEUS and MRI | Cirrhosis, chronic liver disease from HBV, atypical hyperplasia nodules | 4 | 100 | China | 2023 | NCT05286099 | |
| Imaging | n.a. | Short MRI surveillance (SMS) protocol | High-risk cirrhosis and/or chronic liver disease | 4 | 470 | Netherlands | 2026 | NCT05429190 | |
| Clinical test/score, imaging | n.a. | HBsAg, AFP, ultrasound | Populations in Zhongshan City | 5 | 20,000 | China | 2023 | NCT02501980 | |
| Circulating biomarker, clinical test/feature, imaging | FAST-MRI Study | GALAD score, ctDNA, nc-AMRI | Cirrhosis | 4 | 820 | U.S. | 2025 | NCT04539717 | |
| Clinical test/score, imaging | STOP-HCC | GALAD score, ultrasound | Compensated cirrhosis | 4 | 1,600 | Saudi Arabia, Vietnam | 2032 | NCT05342350 | |
| Clinical test/score, imaging | n.a. | AFP, AFP-L3%, DCP, ultrasound, CT | Cirrhosis | 4 | 1,418 | Korea | 2026 | NCT04414956 | |
| Circulating biomarker, clinical test/feature, imaging | n.a. | Genetron HCC Methylation PCR Kit, AFP, ultrasound, MRI | HCC, cirrhosis, chronic liver disease; cirrhosis, chronic liver disease under surveillance | 1-4 | 4,816 | China | 2022 | NCT05343832 | |
| Circulating biomarker, imaging | n.a. | EV-RNA, imaging | HCC, biliary tract cancer, cirrhosis, chronic liver disease | 1/2 | 1,810 | U.S. | 2023 | NCT02908048 | |
| Circulating biomarker | n.a. | Chiroptical, Raman, infrared spectroscopy | HCC, cirrhosis, healty controls | 1/2 | 250 | Czechia | 2022 | NCT04221347 | |
| Monitor change in HCC risk level | Tissue transcriptome, immunostaining biomarker | n.a. | PLS, phospho-EGFR staining | Compensated cirrhosis | 1/2 | 25 | U.S. | 2022 | NCT02273362 |
| Circulating biomarker | n.a. | PLSec | Compensated cirrhosis | 2 | 60 | U.S. | 2026 | NCT05028829 |
ClinicalTrials.gov accessed in July 2022.
HCC, hepatocellular carcinoma; SNP, single nucleotide polymorphism; miRNA, micro RNA; MRI, magnetic resonance imaging; HCV, hepatitis C virus; HBV, hepatitis B virus; NAFLD, non-alcoholic fatty liver disease; ctDNA, circulating tumor DNA; CTC, circulating tumor cell; AMRI, abbreviated MRI; CT, computed tomography; CEUS, contrast-enhanced ultrasound; AFP, alpha-fetoprotein; GALAD, Gender, Age, AFP-L3%, AFP, and DCP; nc-AMRI, non-contrast AMRI; DCP, des-gamma-carboxy prothrombin; EV, extracellular vesicle; PLS, Prognostic Liver Signature; PLSec, Prognostic Liver Secretome Signature.