Original Article
Electronic Pancreas, Biliary Tract, and Liver
Cachexia is Prevalent in Patients With Hepatocellular Carcinoma and Associated With Worse Prognosis

https://doi.org/10.1016/j.cgh.2021.09.022Get rights and content

Background & Aims

Cancer cachexia is a wasting syndrome associated with functional impairment and reduced survival that impacts up to 50% of patients with gastrointestinal cancers. However, data are limited on the prevalence and clinical significance of cachexia in patients with hepatocellular carcinoma (HCC).

Methods

We performed a retrospective cohort study of patients diagnosed with HCC at 2 United States health systems between 2008 and 2018. Patient weights were recorded 6 months prior to and at time of HCC diagnosis. Cachexia was defined as >5% weight loss (or >2% weight loss if body mass index <20 kg/m2), and precachexia was defined as 2% to 5% weight loss. We used multivariable logistic regression models to identify correlates of cachexia and multivariable Cox proportional hazard models to identify factors associated with overall survival.

Results

Of 604 patients with HCC, 201 (33.3%) had precachexia and 143 (23.7%) had cachexia at diagnosis, including 19.0%, 23.5%, 34.7%, and 34.0% of patients with Barcelona Clinic Liver Cancer stages 0/A, B, C, and D, respectively. Patients with cachexia were less likely to receive HCC treatment (odds ratio, 0.38; 95% confidence interval, 0.21–0.71) and had worse survival than those with precachexia or stable weight (11.3 vs 20.4 vs 23.5 months, respectively; P < .001). Cachexia remained independently associated with worse survival (hazard ratio, 1.43; 95% confidence interval, 1.11–1.84) after adjusting for age, sex, race, ethnicity, Child Pugh class, alpha-fetoprotein, Barcelona Clinic Liver Cancer stage, and HCC treatment.

Conclusions

Nearly 1 in 4 patients with HCC present with cachexia, including many with compensated cirrhosis or early stage tumors. The presence of cancer-associated weight loss appears to be an early and independent predictor of worse outcomes in patients with HCC.

Section snippets

Study Cohort

We identified consecutive patients diagnosed with HCC between January 2008 and December 2018 at 2 large United States health systems, the University of Texas Southwestern Medical Center and Parkland Health and Hospital System, using our prospectively maintained institutional database. All HCC diagnoses were confirmed on chart review using the American Association for the Study of Liver Diseases guidelines (ie, characteristic imaging findings [Liver Imaging Reporting and Data System] or

Patient Characteristics

Clinical characteristics of the 604 patients at time of HCC diagnosis are summarized in Table 1. The median age was 60.9 years, 72.2% were male, and over one-half (56.2%) had Child Pugh class A cirrhosis. The cohort was diverse with regard to race and ethnicity (32.1% white, 34.1% black, and 29.0% Hispanic) and tumor stage (58.6% BCLC stage A, 16.3% B, 16.8% C, and 8.3% stage D).

Prevalence and Correlates of Cachexia

At the time of HCC diagnosis, 143 patients (23.7%) had cachexia, including 19.0%, 23.5%, 34.7%, and 34.0% of patients

Discussion

Although cachexia has been identified as an important prognostic factor in several cancers, data are limited on its prevalence and clinical significance in HCC. In this study using clinically granular data from a large and diverse cohort, we found that pretreatment weight loss is prevalent, with 25% of patients experiencing cachexia and 33% of patients having precachexia. Cachexia and precachexia impacted patients across the spectrum of cirrhosis severity and HCC tumor stages, including some

Conclusions

In conclusion, we found 1 in 4 patients with HCC present with cachexia, which appears to be an important prognostic factor in HCC. Given its association with survival, early recognition and treatment of cancer-associated wasting is a potential novel intervention target for reducing mortality in patients with HCC.

CRediT Authorship Contributions

Nicole E. Rich (Conceptualization: Equal; Data curation: Lead; Formal analysis: Equal; Methodology: Equal; Visualization: Lead; Writing – original draft: Lead; Writing – review & editing: Equal)

Samuel Phen (Data curation: Equal; Writing – review & editing: Supporting; data abstraction: Equal)

Nirali Desai (Data curation: Equal; Writing – review & editing: Supporting; data abstraction: Equal)

Sukul Mittal (Data curation: Equal; Writing – review & editing: Supporting; data abstraction: Supporting)

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    Conflicts of interest These authors disclose the following: Nicole Rich serves as a consultant for AstraZeneca. Jorge Marrero has served as a consultant for Glycotest and received research funding from AstraZeneca. Amit Singal has been on advisory boards and served as a consultant for Wako Diagnostics, Roche, Exact Sciences, Glycotest, GRAIL, Bayer, Eisai, Exelixis, BMS, AstraZeneca, Genentech, and TARGET-RWE. Pfizer, Inc. is currently supporting a collaborative project with the laboratory of Rodney Infante that is independent of all data presented in this manuscript. The remaining authors disclose no conflicts.

    Funding Amit G. Singal is supported by National Institutes of Health grants R01 CA222900 and R01 MD12565. Jorge A. Marrero is supported by National Institutes of Health grant R01 CA237659. Rodney E. Infante is supported by Burroughs Wellcome Fund Career Awards for Medical Scientists (1019692); American Gastroenterological Association Scholar Award (2019AGARSA3); American Cancer Society grant (133889-RSG-19-195-01-TBE); Cancer Prevention and Research Institute of Texas (RP200170); and the V Foundation Scholar Award (V2019-014). Nicole E. Rich is supported by the American College of Gastroenterology Junior Faculty Development Award and the Texas Health Resources Clinical Scholar Award. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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