HCC Surveillance: Reevaluating the Evidence and Limitations

The study by Huang et al. makes a significant contribution by demonstrating through a real-world cohort study that surveillance for hepatocellular carcinoma (HCC) is a strong independent predictor of receipt of curative treatment (OR = 17.78) [1]. Furthermore, it reveals that 24% of HBV carriers in the non-surveillance group received their initial infection diagnosis concurrently with their HCC diagnosis, thereby highlighting the disparity between HBV screening and HCC surveillance rates and underscoring the urgency of identifying high-risk populations. However, this study has several methodological limitations that warrant consideration. First, surveillance status was determined solely based on electronic medical records from a single center. Under Taiwan's National Health Insurance system, some patients may have received ultrasound examinations at primary clinics and been misclassified as not under surveillance. Although the authors acknowledged this bias, they did not fully discuss its directional impact on the conclusions. Second, the study did not conduct survival analysis and only reported crude mortality rates, making it impossible to directly assess the impact of surveillance on survival outcomes, thereby limiting the clinical interpretability of the findings. Third, constrained by the small sample size (only 42 cases who did not receive curative treatment), the multivariate model incorporated only a restricted number of covariates. Important variables affecting surveillance adherence, such as socioeconomic factors (e.g., education level, income, and health literacy) and healthcare accessibility, were not collected or adjusted for, raising the possibility of “healthy user bias” [2]. Furthermore, the MASLD subgroup included only 28 cases, resulting in extremely limited statistical power, making the conclusions regarding MASLD patients more descriptive than inferential. The analysis of surveillance intervals may also be affected by reverse causality—where tumor progression leads to elevated AFP levels, subsequently prompting more frequent surveillance, rather than frequent surveillance resulting in the detection of smaller tumors. In response to the above limitations, future research should address these limitations through a multifaceted approach. In the short term, existing follow-up data should be utilized to supplement Kaplan–Meier analysis and Cox regression, providing direct evidence of the impact of surveillance on overall survival; sensitivity analysis should be conducted regarding the classification of surveillance status to test the robustness of the conclusions. In the medium term, multicenter collaboration should be promoted to expand the sample size, particularly by increasing the number of cases in the MASLD and alcoholic liver disease subgroups while simultaneously incorporating socioeconomic variables to adjust for confounding factors. In the long term, given that MASLD has become the primary etiology of HCC in some Western countries, it is recommended to conduct cost-effectiveness analysis of risk stratification strategies based on FIB-4 or transient elastography to identify high-risk MASLD subgroups worthy of surveillance [3, 4]; at the same time, universal HBV screening should be strengthened, and screen-positive individuals should be promptly included in the HCC surveillance system. Overall, this study provides robust evidence on the association of HCC surveillance with early diagnosis and curative treatment based on real-world data. However, issues such as the retrospective design, sample size limitations, and the lack of survival analysis highlight the need for future research to further investigate the optimization of HCC surveillance strategies in the context of changing etiology, based on expanded samples, improved follow-up, and the inclusion of more comprehensive confounding factors. Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.