Sustained Systemic Inflammatory Response Predicts Survival in Patients with Hepatocellular Carcinoma After Hepatic Resection.

Abstract

Preoperative systematic inflammatory response, represented by neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and C-reactive protein-albumin ratio (CAR), has been associated with long-term outcomes in patients with hepatocellular carcinoma (HCC). However, the impact of sustained systematic inflammatory response after resection remains unclear. This study comprised 210 patients who had undergone primary hepatic resection for HCC between 2008 and 2018. Preoperative and postoperative NLR, LMR, and CAR were evaluated, and patients were then classified into three groups according to the status of each marker: persistently high inflammatory state (elevated group), preoperatively low inflammatory state (normal group), and preoperatively high but postoperatively low inflammatory state (normalized group). Multivariate Cox proportional hazard models were conducted to assess disease-free and overall survival, adjusting for potential confounders. In multivariate analysis, sex (p=0.002), hepatitis B surface antigen (HBsAg) positivity (p=0.002), serum α-fetoprotein (AFP) level ≥ 20 ng/mL (p<0.001), multiple tumors (p<0.001), microvascular invasion (p=0.003), type of resection (p=0.007), and elevated CAR (hazard ratio [HR] 2.40, 95% confidence interval [CI] 1.55-3.73; p<0.001) were independent and significant predictors of cancer recurrence, while sex (p=0.05), HBsAg positivity (p=0.03), serum AFP level ≥20 ng/mL (p=0.009), multiple tumors (p=0.03), microvascular invasion (p=0.006), and elevated CAR (HR 2.10, 95% CI 1.13-3.91; p=0.02) were independent predictors of overall survival. Sustained elevated CAR may be an independent and significant indicator of poor long-term outcomes in patients with HCC after hepatic resection, suggesting the interplay of the host's inflammatory state and tumor recurrence and progression in HCC.