Clinicopathological and Prognostic Value of Programmed Cell Death 1 Expression in Hepatitis B Virus-related Hepatocellular Carcinoma: A Meta-analysis

BACKGROUND AND AIMS: The efficacy of targeted programmed cell death 1/programmed death ligand 1 (PD-1/PD-L1) monoclonal antibodies (mAbs) has been confirmed in many solid malignant tumors. The overexpression of PD-1/PD-L1 serves as a biomarker to predict prognosis and clinical progression. However, the role of PD-1 in patients with hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) remains indeterminate. Given that HBV is the most important cause for HCC, this study aimed to investigate the prognostic and clinicopathological value of PD-1 in HBV-HCC via a meta-analysis. METHODS: We searched PubMed, Embase, Scopus, the Cochrane Library, Web of Science and Google Scholar up to January 2021 for studies on the correlation between clinicopathology/prognosis and PD-1 in patients with HBV-HCC. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to investigate the prognostic significance of PD-1 expression. The odds ratios (ORs) and 95% CIs were determined to explore the association between PD-1 expression and clinicopathological features. RESULTS: Our analysis included seven studies with 658 patients, which showed that high PD-1 expression was statistically correlated with poorer overall survival (HR=2.188, 95% CI: [1.262–3.115], p<0.001) and disease-free survival (HR=2.743, 95% CI: [1.980–3.506], p<0.001). PD-1 overexpression was correlated with multiple tumors (OR=2.268, 95% CI: [1.209–4.257], p=0.011), high level of alpha fetoprotein (AFP; OR=1.495, 95% CI: [1.005–2.223], p=0.047) and advanced Barcelona Clinic Liver Cancer (BCLC) stage (OR=3.738, 95% CI: [2.101–6.651], p<0.001). CONCLUSIONS: Our meta-analysis revealed that the high level of PD-1 expression was associated with multiple tumors, high level of AFP and advanced BCLC stage. It significantly predicted a poor prognosis of HBV-HCC, which suggests that anti-PD-1 therapy for HBV-HCC patients is plausible.