Prognostic Significance of Up-to-Seven Criteria Versus Milan Criteria for Hepatocellular Carcinoma Patients Undergoing Resection or Locoregional Therapy: A Systematic Review and Meta-Analysis

Remitha, Ni Putu Sri Indrani; Kusuma, I Komang Wira Ananta; Sasmana, I Gede Aswin Parisya; Supadmanaba, I Gede Putu; Sindhughosa, Dwijo Anargha; Mariadi, I Ketut

doi:10.31557/APJCP.2025.26.11.3909

Prognostic Significance of Up-to-Seven Criteria Versus Milan Criteria for Hepatocellular Carcinoma Patients Undergoing Resection or Locoregional Therapy: A Systematic Review and Meta-Analysis

Document Type : Systematic Review and Meta-analysis

Authors

¹ Faculty of Medicine, Udayana University, Denpasar, Bali, Indonesia.

² Department of Biochemistry, Faculty of Medicine, Udayana University, Denpasar, Bali, Indonesia.

³ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, Udayana University, Bali, Indonesia.

⁴ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, Udayana University/Ngoerah Hospital, Bali, Indonesia.

10.31557/APJCP.2025.26.11.3909

Abstract

Introduction: Every year, the incidence of hepatocellular carcinoma (HCC) rises, making it a persistent global health concern. To help patients with HCC make treatment options for transplant eligibility, a number of selection criteria, including the Milan and Up-to-Seven criteria, have been developed; however, it is unclear how well these predict outcomes. This study aimed to evaluate the prognostic significance of Up-to-Seven versus Milan criteria in HCC patients undergoing resection or locoregional therapy. Methods: In accordance with PRISMA criteria, a systematic review and meta-analysis were performed. The Cochrane Library, PubMed, ScienceDirect, Google Scholar, SpringerLink, and Ebsco were searched for relevant literature. Included were studies contrasting prognostic outcomes (disease-free survival [DFS], progression-free survival [PFS], and overall survival [OS]) according to the two criteria. Review Manager 5.4 was used for data analysis. Results: Five retrospective cohort studies involving 921 patients were analyzed. The meta-analysis revealed a significant difference in OS (HR = 3.42; 95% CI: 2.23–5.25; p < 0.00001) and PFS (HR = 3.39; 95% CI: 1.09–10.54; p = 0.04), favoring the Milan criteria. No significant difference was found in DFS (HR = 2.42; 95% CI: 0.95–6.14; p = 0.06). Conclusion: The Up-to-Seven criteria demonstrated non-inferior prognostic performance to the Milan criteria for DFS, while Milan criteria were associated with significantly better OS and PFS. These findings suggest that the Up-to-Seven criteria may serve as an acceptable alternative in broader patient selection for HCC therapy.

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