Prognostic value of systemic inflammatory markers in patients with resectable hepatocellular carcinoma: a meta-analysis

Preoperative systemic inflammatory markers are inexpensive candidate prognostic factors after hepatocellular carcinoma (HCC) resection, but heterogeneous populations, endpoints, effect measures, and cutoff selection may limit interpretation. Full texts were re-screened using a strict definition of primary HCC treated by first curative-intent hepatic resection. Hazard ratios (HRs) for overall survival (OS), recurrence-free/disease-free survival (RFS/DFS), time to recurrence (TTR), and early recurrence were analyzed separately; binary odds ratios (ORs) were not pooled with HRs. Restricted maximum likelihood random-effects models, 95% prediction intervals, adjusted-estimate sensitivity analyses, subgroup interaction tests, meta-regression, and QUIPS assessments were performed in R 4.4.0. Fifty-one studies met the revised eligibility criteria. Elevated NLR was associated with poorer OS (22 studies; HR = 1.79, 95% CI 1.58–2.02; I2 = 54.7%; 95% prediction interval 1.19–2.68), RFS/DFS (19 studies; HR = 1.60, 95% CI 1.44–1.78; I2 = 35.3%; prediction interval 1.21–2.12), and TTR (6 studies; HR = 1.44, 95% CI 1.27–1.64). Elevated PLR was associated with poorer OS (7 studies; HR = 1.91, 95% CI 1.62–2.25) and RFS/DFS (9 studies; HR = 1.50, 95% CI 1.29–1.76; I2 = 64.3%), although the adjusted-only PLR-RFS/DFS estimate was smaller (HR = 1.19, 95% CI 1.04–1.36). SII was not associated with RFS/DFS in two heterogeneous studies, whereas two cohorts reported an association with shorter TTR. Cutoff subgroup interactions were not significant. Higher preoperative NLR and PLR may be associated with poorer outcomes after primary HCC resection. Residual heterogeneity, data-driven cutoffs, predominantly retrospective Asian cohorts, and risk of bias limit their use as standalone clinical decision tools. Evidence for SII remains sparse and endpoint-dependent.