Neutrophil to lymphocyte and platelet to lymphocyte ratios as biomarkers to predict relapse and survival in posthepatectomy HBV-related hepatocellular carcinoma: a meta-analysis and preliminary immune perspective

BACKGROUND: Hepatitis B virus (HBV) infection represents the major etiology of hepatocellular carcinoma (HCC) and results in poor outcomes. Accumulating evidence suggests that composite immune cell-based biomarkers such as neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) have prognostic value in postoperative HCC patients. However, due to the complexity, differential etiology, and the presence of variable confounding factors in different studies, the relationship between these markers with clinical outcomes in HBV-related posthepatectomy HCC is unclear from an immune perspective. Thus, this meta-analysis was conducted to determine NLR and PLR and assess their relation to overall survival (OS) and recurrence-free survival (RFS) in patients with post-hepatectomy HCC with HBV infection. METHODS: The databases PubMed, Embase, Scopus, and Cochrane Library were searched using relevant keywords. We included studies which compared the outcomes of RFS and OS between different levels of NLR and PLR in HBV-related HCC patients who had undergone hepatectomy. Hazard ratios (HRs) and their 95% confidence intervals (CIs) were considered as effective measures and were calculated by a pooled analysis. Evidence supporting the association of neutrophils, platelets, and lymphocytes with HBV infection, liver injury, and tumor progression in HCC was evaluated. RESULTS: A total of 11 cohort studies with 5083 patients were included. Elevated NLR was significantly associated with poor RFS (HR: 1.28, 95% CI: 1.09–1.50, P=0.000) and poor OS (HR: 1.64, 95% CI: 1.32–2.03, P=0.000). Decreased PLR was significantly associated with a low risk of posthepatectomy relapse (HR: 1.40, 95% CI: 1.28–1.53, P=0.000) and better survival (HR: 1.63, 95% CI: 1.42–1.87, P=0.000). The subgroup and sensitivity analysis showed consistent and stable results. CONCLUSIONS: Both NLR and PLR can be used as biomarkers for the prediction of RFS and OS in patients with HBV-associated HCC after hepatectomy.