Prognostic Significance of Elevated Platelet Count (>200 x 10^9 per L) in BCLC Stages B and C of Hepatocellular Carcinoma: A Retrospective Multicenter Analysis

Stefan Munker,1,2,* Isaac Rodriguez,3,* Kathrin Bernhart,2 Najib Ben Khaled,2 Merve Findik,2 Lisa Katrin Siegmund,2 Liangtao Ye,2 Florian P Reiter,4 Daniel Roessler,2 Daniel Nasseh,5 Lorenz Balcar,6,7 Katharina Pomej,6,7 Bernhard Scheiner,6,7 Christel Weiss,8 Matthias Pinter,6,7 Max Seidensticker,9 Julia Mayerle,2 Alexander B Philipp,2 Enrico N De Toni2 1Department of Pharmacy, Ludwig-Maximilians-Universität Munich, Munich, Germany; 2Department of Medicine II, University Hospital, LMU Munich, Munich, Germany; 3Division of Hepatology, Division of Clinical Bioinformatics, Department of Internal Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; 4Division of Hepatology, Department of Medicine II, University Hospital Würzburg, Würzburg, Germany; 5Comprehensive Cancer Center (CCC Munich LMU), LMU University Hospital Munich, Munich, Germany; 6Department of Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria; 7Vienna Liver Cancer Study Group, Department of Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria; 8Division of Biomedical Informatics, Department of Medical Statistics, Biomathematics, and Information Processing, Center for Preventive and Digital Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; 9Department of Radiology, LMU Klinikum, Ludwig Maximilian University of Munich, Munich, Germany*These authors contributed equally to this workCorrespondence: Stefan Munker, Email [email protected]: In hepatocellular carcinoma (HCC) comorbidities related to decreased liver function or to portal hypertension often limit treatment options. Traditionally, low platelet count has been considered a negative prognostic factor in HCC, especially in early stages. However, recent evidence suggests that elevated platelet count may also predict worse outcomes in advanced stages, suggesting a stage-dependent prognostic impact.Aim: This study evaluated the prognostic role of platelet counts across BCLC stages, adjusted for portal hypertension, to improve individualized patient management.Methods: In this retrospective, multicenter study, platelet count of 1112 patients with HCC in different tumor stages was analyzed. Various platelet count cutoffs (X to Y × 10^9/L) were tested to identify the optimal prognostic threshold. To isolate the effect of platelet levels from portal hypertension, spleen diameter was incorporated as an adjustment variable in multivariate analyses, with variceal status considered when available (in about two thirds of patients). Using an optimized cut-off, survival analysis was performed using univariate and multivariate Cox proportional hazards models. Bootstrapping was performed for internal validation.Results: Platelet count outside 84– 200 × 10^9/L was associated with poorer survival (HR = 0.66, 95% CI = 0.57– 0.78, p < 0.0001). Bootstrapping showed robustness of the final model. Subgroup analysis revealed worse survival in BCLC stages B and C but not stage A for elevated platelet counts (> 200 × 10^9/L) in multivariate analysis (including spleen diameter).Conclusion: Platelet counts showed a stage-dependent prognostic impact in HCC. A platelet count above a cutoff of 200/μL at diagnosis was associated with poorer prognosis. Using this cutoff may improve survival prediction in BCLC B and C patients with potential usage for risk stratification and guidance of treatment decisions. Further external validation is required to confirm these findings and evaluate their clinical applicability.Keywords: hepatocellular carcinoma, HCC, platelets, survival, cutoff, biomarker, BCLC