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SYSTEMATIC REVIEW article

Front. Immunol.

Sec. Cancer Immunity and Immunotherapy

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1695861

The Prognostic and Predictive Value of AFP in Immune Checkpoint Inhibitor-Treated Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Provisionally accepted
Lunjie  YanLunjie Yan1*Bao-Wen  TianBao-Wen Tian2Wei-Chao  LiangWei-Chao Liang1*
  • 1The Sixth Affiliated Hospital of South China University of Technology, Foshan, China
  • 2Qilu Hospital of Shandong University, Jinan, China

The final, formatted version of the article will be published soon.

Introduction: Alpha-fetoprotein (AFP) is a universally recognized tumor marker in hepatocellular carcinoma (HCC). Its utility in assessing the response to immune checkpoint inhibitors (ICIs) remains controversial. This study aims to investigate the predictive value of AFP in ICIs-treated HCC patients. Method: A systematic search strategy was deployed across the PubMed, Embase, Cochrane Library and Web of Science databases. Hazard ratios (HR) or odds ratios (OR) and the corresponding 95% confidence intervals (CIs) were used to assess the pooled risk. Result: The study encompassed a total of 131 studies. Overall survival (OS) (HR=1.60, 95%CI=1.47-1.74), progression-free survival (PFS) (HR=1.35, 95%CI=1.27-1.42), and disease control rate (DCR) (OR=0.50, 95%CI=0.29-0.84) were poorer in ICIs-treated patients with high AFP levels than those with low AFP levels. However, AFP levels were not associated with the objective response rate (ORR) (OR=0.96, 95%CI=0.74-1.24). In addition, patients who achieved an AFP response had favorable OS (HR=0.41, 95%CI=0.33-0.52), PFS (HR=0.38, 95%CI=0.30-0.47), ORR (OR=5.39, 95%CI=3.96-3 7.32) and DCR (OR=5.48, 95%CI=3.71-8.11). Subgroup analyses revealed that AFP>400ng/ml and AFP decline greater than 20% were the most used and efficient cutoff values for high AFP level and AFP response, respectively. Conclusion: High AFP levels are associated with worse outcomes in ICIs-treated HCC. The assessment of AFP response demonstrated promising predictive value for both prognosis and therapeutic response to ICIs. Accurately defining early AFP response remains an area that requires further investigation.

Keywords: Hepatocellular Carcinoma, Immune checkpoint inhibitor, Alpha-Fetoprotein, prognosis, Meta-analysis

Received: 30 Aug 2025; Accepted: 21 Oct 2025.

Copyright: © 2025 Yan, Tian and Liang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Lunjie Yan, 465517762@qq.com
Wei-Chao Liang, lwchng@qq.com

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