Integrating Clinical and Genomic Factors to Predict Hepatocellular Carcinoma Recurrence Following Radical Liver Resection

Surgical resection is the standard therapy for early-stage hepatocellular carcinoma (HCC) in patients with preserved liver function, yet recurrence remains common. While clinical and pathological factors contribute to recurrence risk, HCC is characterized by complex genomic alterations that create significant molecular heterogeneity, which is not yet fully understood. This study sought to combine clinical predictors with molecular insights through next-generation sequencing (NGS) and loss of heterozygosity (LOH) analysis. A cohort of 124 patients who underwent primary liver resection between January 2016 and December 2019 was evaluated. Genomic profiling via NGS and allelic imbalance analysis was performed in a case-control subset. Time-to-recurrence was estimated using Kaplan–Meier methods.

One- and two-year recurrence rates were 21% and 26%, respectively, with Kaplan–Meier estimates of 37% (95% CI: 24–47) and 51% (95% CI: 35–62). Independent clinical predictors of recurrence included HCV infection, elevated bilirubin levels, higher nodule count, and larger nodule size. Interestingly, LOH at the PTEN locus—part of the PI3K/AKT/mTOR pathway—was linked to a decreased recurrence risk (HR: 0.35; 95% CI: 0.13–0.93; p = 0.036). The findings indicate that multiple genomic alterations influence HCC progression. In particular, a specific allelic imbalance detected in 20 patients appeared protective against tumor recurrence. Integrating molecular profiling with clinical assessment may enhance prognostic accuracy and support personalized postoperative management strategies.