Prognostic Biomarkers in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) remains a leading cause of cancer mortality worldwide, driving intensive research into prognostic biomarkers that can guide surveillance, treatment selection and post-treatment monitoring. Traditional markers such as serum alpha-fetoprotein (AFP) have provided a foundation, but their sensitivity and specificity are limited by tumour heterogeneity and underlying liver disease. Recent efforts have expanded the repertoire to include circulating tumour DNA (ctDNA) and circulating tumour cells (CTCs) detectable through liquid biopsy, immune-inflammation indices such as neutrophil-lymphocyte ratio, and composite scores integrating biochemical and clinical parameters. Advances in multi-omic profiling and machine learning have yielded predictive models that combine demographic, molecular and imaging features to stratify risk with greater precision. The ultimate goal is to implement robust, standardised assays capable of identifying minimal residual disease, predicting early recurrence, and tailoring systemic or locoregional therapies according to individual risk profiles. Integration of diverse biomarkers promises personalised prognostication and improved outcomes across heterogeneous patient populations.

Research from Nature Portfolio

Recent large-scale epidemiological analysis of alpha-fetoprotein levels at diagnosis in a national registry has underscored AFP as an independent predictor of pathological grade, tumour progression and survival. Positive AFP status correlated with advanced tumour staging and worse outcomes even after curative surgical interventions, confirming its enduring prognostic utility. Multivariable models demonstrated that AFP positivity retained significance across subgroups, highlighting the need to integrate quantitative AFP assessment within comprehensive prognostic frameworks. This seminal work has provided a robust foundation for combining traditional serum biomarkers with emerging molecular signatures to refine outcome prediction.

Prognostic Biomarkers in Hepatocellular Carcinoma publication trend

The graph below shows the total number of articles in prognostic biomarkers in hepatocellular carcinoma across all publications each year (not limited to Nature Index journals).

Technical terms

Alpha-fetoprotein (AFP): A serum glycoprotein elevated in many HCC patients, used as a conventional prognostic marker.

Circulating tumour DNA (ctDNA): Fragments of tumour-derived DNA in plasma, enabling non-invasive detection of residual disease.

Circulating tumour cells (CTCs): Malignant cells shed into the bloodstream, indicative of metastatic potential and recurrence risk.

Minimal residual disease (MRD): Microscopic cancerous cells persisting after curative therapy, detectable by sensitive liquid-biopsy assays.

CRAFITY score: A prognostic index combining C-reactive protein and AFP levels to predict outcome under immunotherapy.

References

1. Circulating blood biomarkers for minimal residual disease in hepatocellular carcinoma: A systematic review. Cancer Treatment Reviews (2025).
2. Development of a machine learning-based model to predict prognosis of alpha-fetoprotein-positive hepatocellular carcinoma. Journal of Translational Medicine (2024).
3. The prognostic correlation of AFP level at diagnosis with pathological grade, progression, and survival of patients with hepatocellular carcinoma. Scientific Reports (2017).
4. Prognostic significance of neutrophil-lymphocyte ratio in hepatocellular carcinoma: a meta-analysis. BMC Cancer (2014).
5. Prognosis of patients with hepatocellular carcinoma treated with immunotherapy – development and validation of the CRAFITY score. Journal of Hepatology (2021).