Identifying a biologically high-risk subgroup of anatomically resectable hepatocellular carcinoma

Although anatomically resectable hepatocellular carcinoma (HCC) is generally treated with surgery alone, a substantial proportion of patients experience early recurrence, suggesting underlying biological aggressiveness. We aimed to identify a biologically high-risk subgroup among anatomically resectable HCCs and to develop a simple preoperative biology-based risk score.

In this multicenter retrospective cohort study, patients who underwent curative-intent hepatectomy for anatomically resectable HCC were temporally divided into training and validation cohorts. Early recurrence was defined as recurrence within 2 years after surgery. Independent predictors were identified using multivariable logistic regression and incorporated into a risk score. Predictive performance was assessed by recurrence-free survival (RFS), AUC, Akaike information criterion, and calibration analysis.

Alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), and the fibrosis-related host factor FIB-3 were independently associated with early recurrence and were integrated into the ADF (AFP, DCP and FIB-3) score (range, 0-3). In the validation cohort, higher ADF scores were associated with progressively worse RFS (p < 0.001). The ADF score outperformed each individual component alone, showed good calibration, and the addition of tumor size improved discrimination.

The ADF score identifies a biologically high-risk subgroup within anatomically resectable HCC that is prone to early postoperative recurrence. This biology-based framework may complement anatomical assessment and help refine preoperative risk stratification.