Perioperative dynamic changes of systemic inflammatory biomarkers predict tumor recurrence following curative-intent resection of hepatocellular carcinoma

Background: Hepatic inflammation during liver resection induces immune dysregulation. We sought to investigate how surgical stress reshapes systemic inflammation and affects tumor recurrence following surgical resection of hepatocellular carcinoma (HCC). Methods: Patients who underwent curative resection of HCC between 2000 and 2022 were identified from an international multicenter cohort. We longitudinally quantified perioperative inflammatory dynamics, particularly neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII). The primary endpoint was recurrence-free survival (RFS). Model performance was validated through bootstrap resampling (1000 iterations) and ROC analysis. Results: A total of 745 patients were included. Among the dynamic changes of inflammation cells count, only changes in NLR at postoperative day 3 versus preoperative value (Delta NLR3) was identified as a strong predictor associated with HCC recurrence (HR 1.005, 95 % 1.002-1.009; p = 0.002). The optimal cutoff value of Delta NLR3 was defined as 47, and patients with Delta NLR3 >= 47 had 75 % increased risk of tumor recurrence versus individuals with Delta NLR3 < 47 (HR 1.75, 95 % CI 1.35-2.28, p < 0.001). Moreover, Delta NLR3 could be utilized in differentiating high-versus low-recurrence risk patients with early staged HCC. By combining Delta NLR3 with tumor-associated risk factors, we created an InfTumMod model, which demonstrated very good predictive accuracy of 70 % relative to tumor recurrence within the first three years following surgical resection of HCC. Conclusions: The Delta NLR3 index reflected systemic inflammation and risk of tumor recurrence. The InfTumMod model incorporated inflammation index and tumor characteristics, which can help identify patients at higher risk of recurrence and mortality.