Digestive Diseases and Sciences

, Volume 64, Issue 4, pp 918–927 | Cite as

Biomarkers: What Role Do They Play (If Any) for Diagnosis, Prognosis and Tumor Response Prediction for Hepatocellular Carcinoma?

  • James J. HardingEmail author
  • Danny N. Khalil
  • Ghassan K. Abou-Alfa



Hepatocellular carcinoma (HCC) is a common illness that affects patients worldwide. The disease remains poorly understood though several recent advances have increased the understanding of HCC biology and treatment.


A literature review was conducted to understand the role of biomarkers in HCC clinical practice and highlight areas of critical investigation.


Candidate biomarkers may include differential alterations in HCC genomics, epigenomics, gene expression and transcriptomic profiles, protein expression, cellular composition of the microenvironment, and vasculature. To date no circulating or tumor diagnostic markers have been established in this disease. Likewise, prognostication is currently adjudicated by clinicopathologic features and it remains unclear if the incorporation of any biomarkers may help enhance the prognostic understanding following curative intents like surgery, transplant, and select regional therapy or palliative treatment including embolization or systemic therapy. Predictive biomarkers are investigational and are under evaluation for molecular pathways like TOR, MET, VEGFA, and FGF19. Tumoral genomics, HLA allele diversity and tumoral immune activation as predictive markers for immune checkpoint inhibitors are key focuses of ongoing research.


Diagnostic, prognostic, and predictive tumor and circulating biomarkers for HCC have not been defined though several markers have been proposed to guide patient care.


Hepatocellular carcinoma Biomarkers Diagnostic Predictive Prognostic 


Compliance with ethical standards

Conflict of interest

JJH reports consultation fees from Bristol Myers Squibb, Eli Lilly, Eisai, and CtyomX and research funds from Bristol Myers Squibb. GKA reports research support from ActaBiologica, Agios, Array, Astra Zeneca, Bayer, Beigene, BMS, Casi, Celgene, Exelixis, Genentech, Halozyme, Incyte, Lilly, Mabvax, Novartis, OncoQuest, Polaris Puma, QED, Roche; and consulting fees from 3DMedcare, Agios, Alignmed, Amgen, Antengene, Aptus, Aslan, Astellas, Astra Zeneca, Bayer, Beigene, Bioline, BMS, Boston Scientifc, Bridgebio, Carsgen, Celgene, Casi, Cipla, CytomX, Daiichi, Debio, Delcath, Eisai, Exelixis, Genoscience, Gilead, Halozyme, Hengrui, Incyte, Inovio, Ipsen, Jazz, Jansen, Kyowa Kirin, LAM, Lilly, Loxo, Merck, Mina, Newlink Genetcis, Novella, Onxeo, PCI Biotech, Pfizer, Pharmacyte, Pharmacyclics, Pieris, QED, Redhill, Sanofi, Servier, Silenseed, Sillajen, Sobi, Targovax, Tekmira, Twoxar, Vicus, Yakult, and Yiviva.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • James J. Harding
    • 1
    • 2
    Email author
  • Danny N. Khalil
    • 1
    • 2
    • 3
    • 4
  • Ghassan K. Abou-Alfa
    • 1
    • 2
  1. 1.Gastrointestinal Oncology Service, Department of MedicineMemorial Sloan Kettering Cancer CenterNew YorkUSA
  2. 2.Department of MedicineWeill Cornell Medical CollegeNew YorkUSA
  3. 3.Ludwig Center for Cancer ImmunotherapyMemorial Sloan Kettering Cancer CenterNew YorkUSA
  4. 4.Parker Institute for Cancer ImmunotherapyMemorial Sloan Kettering Cancer CenterNew YorkUSA

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