The Prognostic Value of Platelet Count in Patients With Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Abstract

Thrombocytopenia has been acknowledged to be a crucial risk factor for cirrhosis formation and hepatocarcinogenesis in chronic liver diseases. However, to date, the association between platelet count (PLT) and the prognosis of hepatocellular carcinoma (HCC) remains inconsistent and controversial. The aim of the present study was to determine whether PLT could be used as a useful predictor of survival in patients with HCC. We performed systematic review in online databases, including PubMed, EmBase, and Web of Science, from inception until 2014. Studies were included if a statistical relationship was investigated between PLT and survival for HCC, and hazard ratio (HR) and 95% confidence intervals (CIs) for overall survival (OS) or recurrence-free survival (RFS) were provided. The quality of each included study was assessed by Newcastle-Ottawa scale score. To synthesize these studies, a random-effects model or a fixed-effects model was applied as appropriate. Then, we calculated heterogeneity, performed sensitivity analysis, tested publication bias, and did subgrouped and meta-regression analysis. Finally, we identified 33 eligible articles (published from 1998 to 2014) involved 5545 patients by retrieval. A low level of preoperative PLT was found to be significantly associated with a poor survival of HCC. Irrespective of the therapy used, the pooled HRs for OS and RFS were 1.41 (95% CI, 1.14-1.75) and 1.44 (95% CI, 1.13-1.83), respectively. Specifically, in patients who underwent liver resection, the pooled HRs for OS and RFS were 1.67 (95% CI, 1.22-2.27) and 1.44 (95% CI, 1.04-1.99), respectively. Furthermore, patients with preoperative thrombocytopenia (PLT < 100 × 10⁹/L) had a worse OS (HR: 1.73, 95% CI, 1.29-2.32) and RFS (HR: 1.57, 95% CI, 1.31-1.87) in comparison with patients without thrombocytopenia. All our findings showed no significant changes due to the removal of any study or the use of an opposite-effects model, and there was no significant publication bias. The limitations of this meat-analysis were nonuniform cut-off values of PLT, high between-study heterogeneities, potential confounders, and a bias of publication year. A low preoperative PLT level results in an unfavorable outcome in HCC. PLT is a simple, inexpensive, and useful predictor of survival in patients with HCC.

FIGURE 1

Flow diagram of search strategy and study selection.

FIGURE 2

Effects of platelet count on the survival of all HCC patients.

FIGURE 3

Effects of platelet count on the survival of HCC patients who underwent liver resection (A) and RFA (B), the independent effects of platelet count on the survival of HCC patients (C), and the effects of thrombocytopenia on the survival of HCC patients (D).

FIGURE 4

Prognostic significance of platelet count in HCC when it was expressed as a continuous variable.

FIGURE 5

Influence analyses of the overall survival (A) and recurrence-free survival (B) studies in meta-analysis.

FIGURE 6

Begg funnel plot for the overall survival (A) and recurrence-free survival (C) studies, and Egger funnel plot for the overall survival (B) and recurrence-free survival (D) studies.