Prognostic Role of C-Reactive Protein in Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Background: C-reactive protein (CRP) which used to be a prototypical inflammatory cytokine has been identified involving in the progression of tumor-promoting inflammation. Several studies have indicated that CRP is a predictor for hepatocellular carcinoma (HCC), but the results are controversial. Methods: We conducted a systematic review of ten studies (1885 patients) to examine the association of high serum CRP expression with overall survival (OS) and recurrence-free survival (RFS) in HCC patients by meta-analysis. Moreover, the correlation between high serum CRP and tumor clinicopathological parameters was also assessed. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was used as the effect size estimate. Results: Our pooled results showed that high expression level of serum CRP (≥10 mg/L) was associated with poor OS (HR: 2.15, 95% CI: 1.76-2.63) and RFS (HR: 2.66, 95% CI: 1.54-4.58) in HCC. Serum CRP overexpression (≥10 mg/L) was also significantly associated with the presence of tumor vascular invasion (OR: 3.05, 95% CI: 1.79-5.23), multiple tumor (OR: 2.36, 95% CI: 1.36-4.10), larger tumor size (OR: 3.41, 95% CI: 1.04-11.18), and advanced TNM stage (OR: 3.23, 95% CI: 2.29-4.57). In addition, serum CRP overexpression (≥10 mg/L) tended to be correlated with poor differentiation (OR: 1.58, 95% CI: 0.74-3.39), though not significantly. Conclusion: The present systematic review and meta-analysis demonstrate that high serum level of CRP (≥10 mg/L) denotes a poor prognosis of patients with HCC.