Preoperative gamma-glutamyltransferase-to-lymphocyte ratio and prognosis after curative hepatectomy for hepatocellular carcinoma: a systematic review and meta-analysis

BACKGROUND: Preoperative inflammatory and liver-function-related biomarkers are widely used for risk stratification in hepatocellular carcinoma (HCC), but the prognostic role of the gamma-glutamyltransferase-to-lymphocyte ratio (GLR) after curative hepatectomy has not been systematically synthesized. METHODS: We performed a systematic review and meta-analysis of studies evaluating preoperative GLR in adults undergoing curative hepatectomy for HCC. PubMed, Embase, Web of Science Core Collection, China National Knowledge Infrastructure (CNKI), and Wanfang were searched from inception to 16 March 2026, without language or date restrictions. The protocol was registered in PROSPERO (CRD420261345926). Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled using inverse-variance DerSimonian-Laird random-effects models, with fixed-effect models examined as sensitivity analyses. The primary outcomes were overall survival (OS) and recurrence-related outcomes. Strict endpoint-specific analyses for disease-free survival (DFS), recurrence-free survival (RFS), and progression-free survival (PFS) were also performed. RESULTS: A total of 141 records were identified, and 98 unique records remained after removal of 43 duplicates. Twelve full-text articles were assessed and included in the qualitative synthesis; seven studies with conventional fixed hazard ratios were eligible for the primary quantitative meta-analysis. Elevated preoperative GLR remained significantly associated with worse OS(random-effects HR 2.07, 95% CI 1.73-2.49; I²=33.6%) and poorer recurrence-related outcomes (random-effects HR 1.74, 95% CI 1.51-2.01; I²=7.2%). Exploratory subgroup analyses suggested that study-level cut-off variation was not a major source of heterogeneity, and although several studies used thresholds around 39-45, this pattern was not sufficiently consistent across all hepatectomy cohorts to support a standardized clinical cutoff. CONCLUSIONS: Preoperative GLR is a clinically accessible adverse prognostic factor for OS and recurrence-related outcomes after curative hepatectomy for HCC. The available evidence supports its potential use in postoperative risk stratification, although the predominance of retrospective single-center studies from China, heterogeneity in GLR cutoffs, and limited numbers of studies in endpoint-specific analyses warrant cautious interpretation. While several studies used thresholds around 39-45, the current evidence remains insufficient to define a universal clinical cutoff, and a value near 40 should be regarded only as a pragmatic candidate for future validation.