The Definition of the Best Margin Cutoff and Related Oncological Outcomes After Liver Resection for Hepatocellular Carcinoma: A Systematic Review

: Background/Objectives: Different cutoffs have been proposed to be the optimal resection margin of liver resection for hepatocellular carcinoma (HCC). The aim of this study was to perform a systematic review, investigating the different impacts on disease-free survival (DFS) and overall survival (OS) of different margin cutoffs. Methods: The PubMed, Embase, and Cochrane databases were searched for comparative studies evaluating the oncological impacts of different types of liver resection margin for HCC. Results: A total of 48 studies were included in the final analysis. Among them, 36 evaluated the impact of resection margin width on OS and 42 on DFS. The margin cutoffs assessed varied widely, including 20 mm, 10 mm, 5 mm, 4 mm, 2 mm, and 1 mm. While wider margins (≥10 mm) were generally associated with improved outcomes, particularly in high-risk subgroups such as patients with microvascular invasion (MVI), elevated alpha-fetoprotein (AFP) levels, or a non-cirrhotic liver, other studies reported no significant differences. The findings were highly heterogeneous across the studies due to differences in patient populations, tumor biology, and surgical approaches. Consequently, the evidence suggests that the optimal margin is context-dependent rather than universal. Conclusions: Wider resection margins should be considered in select high-risk patients, while a tailored, case-by-case approach remains necessary given the overall heterogeneity of HCC presentations.