Liver Dysfunction Explains a Substantial Proportion of Circulating cfDNA Variability in HCC: An Exploratory Study

Area of Science:

• Oncology
• Hepatology
• Biomarker Discovery

Background:

• Circulating cell-free DNA (cfDNA) shows promise as a minimally invasive biomarker for hepatocellular carcinoma (HCC).
• Understanding cfDNA variability in relation to liver dysfunction and tumor stage is crucial for its clinical application.

Purpose of the Study:

• To evaluate the relationship between cfDNA concentration, liver dysfunction parameters, and HCC stage.
• To determine if cfDNA offers incremental information beyond standard markers for discriminating early vs. late-stage HCC.

Main Methods:

• Sixty-four newly diagnosed HCC patients were analyzed.
• Plasma cfDNA was quantified; clinical, laboratory, and staging data were collected.
• Logistic regression, ROC curve analysis, and bootstrap resampling were used for biomarker panel evaluation.

Main Results:

• Liver dysfunction parameters explained approximately 53% of cfDNA variability; HCC stage had minimal impact.
• Albumin, bilirubin, and platelet count achieved AUROCs up to 0.857 for discriminating HCC stages.
• cfDNA concentration slightly increased specificity but reduced sensitivity for early vs. advanced HCC discrimination and was an unstable predictor.

Conclusions:

• cfDNA concentration in HCC patients is significantly influenced by the underlying liver disease environment and hepatocyte injury, rather than tumor burden alone.
• Integrated multimarker panels combining liver reserve parameters and etiology may aid in minimally invasive HCC stratification.
• The incremental value of cfDNA for discriminating HCC stages is low, requiring further validation in larger prospective cohorts.