The Influence of Visceral Adiposity on Overall Survival: Exploring “Obesity Paradox” Among Hepatocellular Carcinoma Patients Who Receiving Immunotherapy

Abstract

Purpose

The impact of visceral adiposity on overall survival (OS) in hepatocellular carcinoma (HCC) receiving immunotherapy was unclear. We aimed to determine how visceral adiposity affected OS and explore the interrelationships between visceral adiposity, body mass index (BMI), and other body compositions.

Patients and Methods

Data from three centers were retrospectively analyzed. Skeletal muscle index (SMI), skeletal muscle density (SMD), visceral adipose tissue index (VATI), and subcutaneous adipose tissue index (SATI) were used to define each body composition. The BMI subgroups included the underweight, the normal weight, and the obesity. The Log rank test compared survival curves calculated by the Kaplan-Meier method. The relationships between body compositions and BMI with OS were examined using Cox proportional risk regression models.

Results

A total of 305 patients who met the criteria were included. Patients with low VATI had significantly worse OS (P = 0.001). The protections of VATI (P = 0.011) on OS were independent of covariates. However, after additional adjustment of SMI, the effect of VATI on OS disappeared (P = 0.146), but the effect of SMD on OS did not (P = 0.021). BMI has a significant U-shaped relationship with OS, and the effect of BMI on OS equally disappeared after additional adjustment by SMI.

Conclusion

This study first demonstrated that high VATI and mid-level BMI were protective for the survival of patients with HCC receiving immunotherapy. Skeletal muscle status (including SMI and SMD) may be the better predictor for outcomes of patients with HCC receiving immunotherapy.

Keywords:

• hepatocellular carcinoma
• immunotherapy
• body mass index
• body composition
• obesity paradox

Data Sharing Statement

All data will be available from the corresponding author Jinxue Zhou ([email protected]) on reasonable request.

Ethics Approval and Informed Consent

This retrospective study was approved by the Medical Ethics Committee of Henan Cancer Hospital (No. 2023-KY-0075-002), and was conducted by the Declaration of Helsinki (as revised in 2013). All participating institutions were informed and agreed with the study. The requirement for patient consent was waived because the study was retrospective and all data was anonymized or maintained with confidentiality of patients.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

All authors have no conflicts of interest to declare in this work.

Additional information

Funding

This work was sponsored by the Henan Provincial Medical Science and Technology Research Project (LLRGJ20220191, LHGJ20200171), the Henan Provincial Science and Technology Project (232102311080, 222102310341), the Key Scientific Research Project of Colleges and Universities in Henan Province (23A320033), the National Key Research and Development Program of China (2023YFC3403800), the National Natural Science Foundation of China (No. 81972311, 82141127), the CAMS Innovation Fund for Medical Sciences (CIFMS) (No. 2021-I2M-1-066), the Non-profit Central Research Institution Fund of Chinese Academy of Medical Sciences (No. 2019PT310026).