A comment on “Association of physical activity, including amount and maintenance, with the risk of HCC among patients with type 2 diabetes”

To the Editor:

The recent research paper by Han et al.¹ published in JHEP Reports, caught our attention. This study stands out as one of the first to comprehensively evaluate the relationship between physical activity (PA) levels and hepatocellular carcinoma (HCC) risk in patients with diabetes. The study utilized a large, nationwide cohort and investigated both the amount and changes in PA, providing critical insights into how sustained PA can reduce HCC risk in this vulnerable population. Han et al. found that patients who maintained persistently high levels of PA had a significantly lower risk of HCC compared to those who were inactive, highlighting the protective effect of consistent exercise. These results are highly significant, offering a valuable preventive strategy for clinicians managing patients with type 2 diabetes, who are at higher risk of liver cancer. While the thorough methodology and important contributions of this study are deeply appreciated, a few constructive suggestions are proposed for further refinement.

First, while the study effectively used the Cox proportional hazards model to assess the association between PA and the risk of HCC, it did not utilize a pooled logistic regression model with flexible time-dependent parameters to explore the potential short-term associations or effects.^2,3 This model would allow for a more dynamic analysis by accounting for how the relationship between PA and HCC risk may change over time. Including both Cox and pooled logistic regression models would strengthen the analysis by offering a more comprehensive view of both long-term and short-term risk associations.

Second, while the authors adjusted for various important covariates, the absence of stratified analyses based on diabetes duration and diabetes medication use could be an area for further exploration.⁴ Performing stratified analyses based on these factors would provide deeper insights into how different levels of diabetes management interact with the protective effects of PA, particularly in relation to HCC as a key outcome. Moreover, validation through accelerometer-derived PA data, which has demonstrated a dose-response relationship with reduced type 2 diabetes risk,⁵ would offer stronger evidence. Previous studies have also shown that accelerometer-measured PA is inversely associated with hepatic fibrosis and inflammation,⁶ as well as liver disease risk,⁷ further supporting its relevance in HCC-related analyses. As this is a retrospective study, it is understandable that such data may not have been available. However, we look forward to seeing how the authors might incorporate accelerometer-derived PA data in future research, which would undoubtedly further strengthen the robustness of their already impactful findings.

Third, type 2 diabetes and HCC are influenced by various metabolic and inflammatory factors,^8,9 including glucose metabolism, lipid metabolism, and inflammation levels, all of which may be modulated by PA. Understanding the role of these factors in relation to PA could provide deeper insights into how sustained PA influences HCC risk.

In conclusion, Han et al.’s study provides a significant contribution to the understanding of physical activity’s role in reducing HCC risk in patients with type 2 diabetes. The large-scale cohort and analysis of PA changes offer invaluable insights for clinical practice. Future studies could build on these findings by exploring the potential time-dependent effects of PA using pooled logistic regression models and performing stratified analyses based on diabetes management. Additionally, the use of accelerometer-derived PA data could further validate the protective effects of physical activity. We commend the authors for their impactful research and look forward to future studies addressing these aspects.

Financial support

This work was financially supported by a grant from Health Commission of Zhejiang Province Traditional Chinese Medicine Science and Technology Project (2021ZA107). This work was financially supported by a grant from Health Commission of Zhejiang Chinese Medical University Hangzhou Hospital of Traditional Chinese Medical (2020SJZDXK13).

Authors’ contribution

Z.W.G., J.C.Q., and W.Y.: conception and design; Z.W.G. and J.C.Q.: collected and analyzed the data; Z.W.G. and J.C.Q.: wrote the paper. All the authors drafted and revised the manuscript and also read and approved the final version.

Conflict of interest

The authors declare no conflicts of interest that pertain to this work.

Please refer to the accompanying ICMJE disclosure forms for further details.

Supplementary data

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