FROM BIOMARKERS TO PRECISION SURVEILLANCE: A SOCIO-TECHNICAL REVIEW OF NON-INVASIVE HEPATOCELLULAR CARCINOMA SCREENING IN CIRRHOSIS
DOI:
https://doi.org/10.31435/ijitss.1(49).2026.5352Keywords:
Hepatocellular Carcinoma, Precision Surveillance, Biomarkers, Cirrhosis, Implementation, Health EquityAbstract
This review examines how non-invasive biomarker technologies are reshaping hepatocellular carcinoma (HCC) surveillance in cirrhosis when considered not only as diagnostic tools but also as socio-technical interventions. A structured narrative review was developed from a targeted full-text corpus covering biomarkers, precision surveillance, cost-effectiveness, surveillance harms, and disparities in access and outcomes. The literature was coded thematically across five domains: biomarker technologies, precision surveillance models, economic value, patient burden, and equity and implementation. The reviewed evidence shows that surveillance is moving from a one-size-fits-all ultrasound-based model toward hybrid, risk-stratified systems that combine blood-based biomarkers, algorithmic scores, and selective advanced imaging. Composite scores such as GALAD and HES V2.0 improve early-stage detection compared with single markers, while recent modeling studies suggest that biomarker-based or precision surveillance can be cost-effective under realistic assumptions about test performance, adherence, and price. However, adoption is constrained by assay standardization, reimbursement, false-positive workup, psychological and financial harms, and persistent disparities related to insurance, mental health, transportation, language, and digital access. The main conclusion is that the future of HCC screening is not simply a better biomarker but a better surveillance system. Research and policy should therefore evaluate analytic performance together with workflow fit, patient acceptability, equity, governance, and real-world implementation.
References
Amin, N., Anwar, J., Sulaiman, A., Naumova, N. N., & Anwar, N. (2025). Hepatocellular carcinoma: A comprehensive review. Diseases, 13(7), Article 207. https://doi.org/10.3390/diseases13070207
Atiq, O., Tiro, J., Yopp, A. C., Muffler, A., Marrero, J. A., Parikh, N. D., Murphy, C. C., McCallister, K., & Singal, A. G. (2017). An assessment of benefits and harms of hepatocellular carcinoma surveillance in patients with cirrhosis. Hepatology, 65(4), 1196–1205. https://doi.org/10.1002/hep.28895
Decharatanachart, P., Pan-ngum, W., Peeraphatdit, T., Tanpowpong, N., Tangkijvanich, P., Treeprasertsuk, S., Rerknimitr, R., & Chaiteerakij, R. (2024). Cost-utility analysis of non-contrast abbreviated magnetic resonance imaging for hepatocellular carcinoma surveillance in cirrhosis. Gut and Liver, 18(1), 135–146. https://doi.org/10.5009/gnl230089
Huang, D. Q., Singal, A. G., Kanwal, F., Lampertico, P., Buti, M., Sirlin, C. B., Nguyen, M. H., & Loomba, R. (2023). Hepatocellular carcinoma surveillance—utilization, barriers and the impact of changing aetiology. Nature Reviews Gastroenterology & Hepatology, 20(12), 797–809. https://doi.org/10.1038/s41575-023-00818-8
Jaber, F., & El-Serag, H. B. (2025). HES V2.0 surpasses GALAD for HCC detection: A review of multidimensional biomarker scores and studies. Hepatic Oncology, 12(1), Article 2494446. https://doi.org/10.1080/20450923.2025.2494446
Kao, S.-Y. Z., Sangha, K., Fujiwara, N., Hoshida, Y., Parikh, N. D., & Singal, A. G. (2024). Cost-effectiveness of a precision hepatocellular carcinoma surveillance strategy in patients with cirrhosis. EClinicalMedicine, 75, Article 102755. https://doi.org/10.1016/j.eclinm.2024.102755
Kronenfeld, J. P., & Goel, N. (2021). An analysis of individual and contextual-level disparities in screening, treatment, and outcomes for hepatocellular carcinoma. Journal of Hepatocellular Carcinoma, 8, 1209–1219. https://doi.org/10.2147/JHC.S284430
Lee, Y.-T., Fujiwara, N., Yang, J. D., & Hoshida, Y. (2023). Risk stratification and early detection biomarkers for precision HCC screening. Hepatology, 78(1), 319–362. https://doi.org/10.1002/hep.32779
Marquardt, P., Liu, P. H., Immergluck, J., Olivares, J., Arroyo, A., Rich, N. E., Parikh, N. D., Yopp, A. C., & Singal, A. G. (2021). Hepatocellular carcinoma screening process failures in patients with cirrhosis. Hepatology Communications, 5(9), 1481–1489. https://doi.org/10.1002/hep4.1735
Marsh, T. L., Parikh, N. D., Roberts, L. R., Schwartz, M. E., Nguyen, M. H., Befeler, A., Page-Lester, S., Tayob, N., Srivastava, S., Rinaudo, J. A., Singal, A. G., Reddy, K. R., & Marrero, J. A. (2025). A phase 3 biomarker validation of GALAD for the detection of hepatocellular carcinoma in cirrhosis. Gastroenterology, 168(2), 316–326.e6. https://doi.org/10.1053/j.gastro.2024.09.008
Narasimman, M., Hernaez, R., Cerda, V., Lee, M., Sood, A., Yekkaluri, S., Khan, A., Quirk, L., Liu, Y., Kramer, J. R., Craddock Lee, S., Murphy, C. C., Tiro, J. A., & Singal, A. G. (2024). Hepatocellular carcinoma surveillance may be associated with potential psychological harms in patients with cirrhosis. Hepatology, 79(1), 107–117. https://doi.org/10.1097/HEP.0000000000000528
Narasimman, M., Hernaez, R., Cerda, V., Lee, M., Yekkaluri, S., Khan, A., Sood, A., Gurley, T., Quirk, L., Liu, Y., Kramer, J. R., Craddock Lee, S., Tiro, J. A., Murphy, C. C., & Singal, A. G. (2024). Financial burden of hepatocellular carcinoma screening in patients with cirrhosis. Clinical Gastroenterology and Hepatology, 22(4), 760–767.e1. https://doi.org/10.1016/j.cgh.2023.07.018
Saleh, S., Mohammed, A., Davila, J., Paranji, N., & Niu, B. (2022). Disparities in hepatocellular cancer screening in cirrhotic patients with psychiatric disorders. Cureus, 14(3), Article e23516. https://doi.org/10.7759/cureus.23516
Singal, A. G., Chen, Y., Sridhar, S., Mittal, V., Fullington, H., Shaik, M., Waljee, A. K., & Tiro, J. A. (2022). Novel application of predictive modeling: A tailored approach to promoting HCC surveillance in patients with cirrhosis. Clinical Gastroenterology and Hepatology, 20(8), 1795–1802.e2. https://doi.org/10.1016/j.cgh.2021.02.038
Singal, A. G., Chhatwal, J., Parikh, N. D., & Tapper, E. B. (2024). Cost-effectiveness of a biomarker-based screening strategy for hepatocellular carcinoma in patients with cirrhosis. Liver Cancer, 13(6), 643–654. https://doi.org/10.1159/000539895
Singal, A. G., Reig, M., & Villanueva, A. (2022). Emerging tools for hepatocellular carcinoma surveillance. American Journal of Gastroenterology, 117(12), 1948–1951. https://doi.org/10.14309/ajg.0000000000002015
Singal, A. G., Sanduzzi-Zamparelli, M., Nahon, P., Ronot, M., Hoshida, Y., Rich, N., Reig, M., Vilgrain, V., Marrero, J., Llovet, J. M., Parikh, N. D., & Villanueva, A. (2023). International Liver Cancer Association (ILCA) white paper on hepatocellular carcinoma risk stratification and surveillance. Journal of Hepatology, 79(1), 226–239. https://doi.org/10.1016/j.jhep.2023.02.022
Wolf, E., Rich, N. E., Marrero, J. A., Parikh, N. D., & Singal, A. G. (2021). Use of hepatocellular carcinoma surveillance in patients with cirrhosis: A systematic review and meta-analysis. Hepatology, 73(2), 713–725. https://doi.org/10.1002/hep.31309
Woolen, S. A., Singal, A. G., Davenport, M. S., Troost, J. P., Khalatbari, S., Mittal, S., Siddiqui, S., Fobar, A., Morris, J., Odewole, M., Tapper, E. B., Pillai, A., & Parikh, N. D. (2022). Patient preferences for hepatocellular carcinoma surveillance parameters. Clinical Gastroenterology and Hepatology, 20(1), 204–215.e6. https://doi.org/10.1016/j.cgh.2021.02.024
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Kamil Chudzicki, Michał Babicz, Oliwer Muller, Jagoda Pałubska, Katarzyna Rosa, Agata Słoma, Anna Szot, Dominik Szydełko, Martyna Szymczyk, Paweł Żurek
This work is licensed under a Creative Commons Attribution 4.0 International License.
All articles are published in open-access and licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Hence, authors retain copyright to the content of the articles.
CC BY 4.0 License allows content to be copied, adapted, displayed, distributed, re-published or otherwise re-used for any purpose including for adaptation and commercial use provided the content is attributed.
How to Cite
