Sierra L, Abu-Hammour MN, Chatterjee A, Simons-Linares CR. Obesity paradox role in the immunosuppressive treatment of hepatocellular carcinoma. World J Gastroenterol 2025; 31(19): 105617 [DOI: 10.3748/wjg.v31.i19.105617]
Corresponding Author of This Article
C Roberto Simons-Linares, MD, Senior Researcher, Department of Gastroenterology and Hepatology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, United States. simonsc@ccf.org
Research Domain of This Article
Research & Experimental Medicine
Article-Type of This Article
Letter to the Editor
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. May 21, 2025; 31(19): 105617 Published online May 21, 2025. doi: 10.3748/wjg.v31.i19.105617
Obesity paradox role in the immunosuppressive treatment of hepatocellular carcinoma
Leandro Sierra, Mohamad-Noor Abu-Hammour, Arjun Chatterjee, C Roberto Simons-Linares
Leandro Sierra, Mohamad-Noor Abu-Hammour, Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, OH 44195, United States
Arjun Chatterjee, C Roberto Simons-Linares, Department of Gastroenterology and Hepatology, Cleveland Clinic Foundation, Cleveland, OH 44195, United States
Author contributions: Sierra L contributed to conceptualization, project administration, formal analysis, and visualization; Abu-Hammour MN contributed to formal analysis; Sierra L, Abu-Hammour MN, and Chatterjee A contributed to data curation, and wrote the original draft; Simons-Linares CR contributed to conceptualization, methodology, supervision, validation, and visualization; and all authors have reviewed, and edited the draft, read and agreed to the published version of the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: C Roberto Simons-Linares, MD, Senior Researcher, Department of Gastroenterology and Hepatology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, United States. simonsc@ccf.org
Received: January 30, 2025 Revised: March 15, 2025 Accepted: April 1, 2025 Published online: May 21, 2025 Processing time: 111 Days and 10 Hours
Abstract
The “obesity paradox” in hepatocellular carcinoma (HCC) suggests patients with obesity may experience better treatment outcomes compared to patients without obesity. Wang et al highlighted this paradox in HCC immunotherapy, demonstrating superior progression-free survival and overall survival in patients with overweight and obesity treated with lenvatinib and camrelizumab, focusing on hepatitis B virus-related HCC. Mechanisms such as better nutritional reserves, leptin-mediated immune modulation, and reduced protein breakdown may explain these outcomes. Obesity’s role in anti-programmed cell death protein-1 therapy appears could have a benefit, while its effects on other treatments, such as anti-vascular endothelial growth factor therapy, may reduce efficacy. Further research is needed to explore how obesity influences the effectiveness of other most common immunotherapies like nivolumab, pembrolizumab, and bevacizumab, and whether weight loss as well as weight-loss related sarcopenia impacts these benefits.
Core Tip: The “obesity paradox” in hepatocellular carcinoma suggests better outcomes in patients with obesity undergoing immunotherapy, potentially due to leptin-driven immune modulation and enhanced nutritional reserves. While promising, these findings have only been demonstrated with lenvatinib and camrelizumab, and have not yet been observed with more commonly used immunotherapy treatments for hepatocellular carcinoma, such as nivolumab, pembrolizumab, or bevacizumab. Although intriguing, this phenomenon remains limited by the scope of current studies.
