Retrospective Cohort Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Mar 27, 2024; 16(3): 393-404
Published online Mar 27, 2024. doi: 10.4254/wjh.v16.i3.393
Lean body mass index is a marker of advanced tumor features in patients with hepatocellular carcinoma
Andrew Scott deLemos, Jing Zhao, Milin Patel, Banks Kooken, Karan Mathur, Hieu Minh Nguyen, Areej Mazhar, Maggie McCarter, Heather Burney, Carla Kettler, Naga Chalasani, Samer Gawrieh
Andrew Scott deLemos, Milin Patel, Banks Kooken, Department of Medicine, Atrium Health, Charlotte, NC 28204, United States
Jing Zhao, Maggie McCarter, Center for Outcomes Research and Evaluation, Atrium Health, Charlotte, NC 28204, United States
Karan Mathur, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, United States
Hieu Minh Nguyen, Center for Health System Sciences (CHASSIS), Atrium Health, Charlotte, NC 28204, United States
Areej Mazhar, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, United States
Heather Burney, Carla Kettler, Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, IN 46202, United States
Naga Chalasani, Samer Gawrieh, Department of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN 46202, United States
Author contributions: deLemos AS, Gawrieh S, and Chalasani N conceived the study, analyzed data, and contributed to draft and final manuscript preparation; Zhao J, and Nguyen HM provided statistical analysis, critical appraisal of data, and manuscript editing; Patel M, Kooken B, Mathur K, Mazhar A, Burney H, and Kettler C assisted with tumor registry data entry and maintenance of database; McCarter M assisted with statistical analysis.
Supported by in part David W Crabb Professorship Endowment at Indiana University School of Medicine and an intramural grant from the Atrium Health Center for Outcomes Research and Evaluation (CORE) (to deLemos AS).
Institutional review board statement: Each participating site had local Institutional Review Board approval to conduct the study.
Informed consent statement: This study was retrospective and did not have any direct patient contact and was completely deidentified.
Conflict-of-interest statement: Dr. Gawrieh consulting: TransMedics, Pfizer, research grant support: Cirius, Galmed and Zydus. Dr. Chalasani had paid consulting activities with following companies in last 12 months: Abbvie, Madrigal, Galectin, Zydus, Boehringer-Ingelheim, and Altimmune. He and his institution receive research funding from DSM, Exact Sciences, and Galectin. The remaining authors have no conflicts of interests to declare in the last 12 months.
Data sharing statement: A data sharing agreement was established between Atrium Health and Indiana University School of Medicine for the purpose of compiling a de-identified patient registry.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
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: Andrew Scott deLemos, MD, Associate Professor, Department of Medicine, Atrium Health, 1025 Morehead Medical Drive, Suite 600, Charlotte, NC 28204, United States. andrew.delemos@atriumhealth.org
Received: November 15, 2023
Peer-review started: November 15, 2023
First decision: November 27, 2023
Revised: December 31, 2023
Accepted: February 23, 2024
Article in press: February 23, 2024
Published online: March 27, 2024
Processing time: 132 Days and 15.2 Hours
Abstract
BACKGROUND

Obesity is an independent risk factor for the development of hepatocellular carcinoma (HCC) and may influence its outcomes. However, after diagnosis of HCC, like other malignancies, the obesity paradox may exist where higher body mass index (BMI) may in fact confer a survival benefit. This is frequently observed in patients with advanced HCC and cirrhosis, who often present late with advanced tumor features and cancer related weight loss.

AIM

To explore the relationship between BMI and survival in patients with cirrhosis and HCC.

METHODS

This is a retrospective cohort study of over 2500 patients diagnosed with HCC between 2009-2019 at two United States academic medical centers. Patient and tumor characteristics were extracted manually from medical records of each institutions' cancer registries. Patients were stratified according to BMI classes: < 25 kg/m2 (lean), 25-29.9 kg/m2 (overweight), and > 30 kg/m2 (obese). Patient and tumor characteristics were compared according to BMI classification. We performed an overall survival analysis using Kaplan Meier by the three BMI classes and after adjusting for Milan criteria. A multivariable Cox regression model was then used to assess known risk factors for survival in patients with cirrhosis and HCC.

RESULTS

A total of 2548 patients with HCC were included in the analysis of which 11.2% (n = 286) were classified as non-cirrhotic. The three main BMI categories: Lean (n = 754), overweight (n = 861), and obese (n = 933) represented 29.6%, 33.8%, and 36.6% of the total population overall. Within each BMI class, the non-cirrhotic patients accounted for 15% (n = 100), 12% (n = 94), and 11% (n = 92), respectively. Underweight patients with a BMI < 18.5 kg/m2 (n = 52) were included in the lean cohort. Of the obese cohort, 42% (n = 396) had a BMI ≥ 35 kg/m2. Out of 2262 patients with cirrhosis and HCC, 654 (29%) were lean, 767 (34%) were overweight, and 841 (37%) were obese. The three BMI classes did not differ by age, MELD, or Child-Pugh class. Chronic hepatitis C was the dominant etiology in lean compared to the overweight and obese patients (71%, 62%, 49%, P < 0.001). Lean patients had significantly larger tumors compared to the other two BMI classes (5.1 vs 4.2 vs 4.2 cm, P < 0.001), were more likely outside Milan (56% vs 48% vs 47%, P < 0.001), and less likely to undergo transplantation (9% vs 18% vs 18%, P < 0.001). While both tumor size (P < 0.0001) and elevated alpha fetoprotein (P < 0.0001) were associated with worse survival by regression analysis, lean BMI was not (P = 0.36).

CONCLUSION

Lean patients with cirrhosis and HCC present with larger tumors and are more often outside Milan criteria, reflecting cancer related cachexia from delayed diagnosis. Access to care for hepatitis C virus therapy and liver transplantation confer a survival benefit, but not overweight or obese BMI classifications.

Keywords: Hepatocellular carcinoma; Cirrhosis; Obesity; Body mass index class; Sarcopenia; Chronic hepatitis C

Core Tip: This study explores the impact of different body mass index (BMI) strata on patient survival following the diagnosis of hepatocellular carcinoma (HCC). We stratified patients with cirrhosis by lean (BMI < 25 kg/m2), overweight BMI (25-29.9 kg/m2), and obese (BMI ≥ 30 kg/m2) categories, and analyzed patient and tumor characteristics. Lean patients with HCC presented with significantly larger tumors as well as more advanced tumors. Survival was significantly reduced in lean HCC patients in the overall cohort but was restricted to those patients outside Milan criteria following sub-group analysis. We included a survival analysis by BMI class according to the three most common chronic liver diseases: Chronic hepatitis C, alcoholic liver disease, and nonalcoholic fatty liver disease. Lastly, we found no significant difference in survival comparing the three BMI classes from our sub-group of 286 patients with HCC but without cirrhosis.