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Obesity is Independently Associated With Increased Risk of Hepatocellular Cancer–related Mortality: A Systematic Review and Meta-Analysis

Gupta, Arjun, MD*; Das, Avash, MBBS; Majumder, Kaustav, MD; Arora, Nivedita, MD*; Mayo, Helen G., MLS§; Singh, Preet P., MD; Beg, Muhammad S., MD, MS; Singh, Siddharth, MD, MS#

American Journal of Clinical Oncology: September 2018 - Volume 41 - Issue 9 - p 874–881
doi: 10.1097/COC.0000000000000388
Original Articles: Gastrointestinal

Objective: Excess body weight is associated with increased risk of developing hepatocellular cancer (HCC), but its effect on HCC-related mortality remains unclear. We performed a systematic review and meta-analysis to assess the association between premorbid obesity and HCC-related mortality.

Materials and Methods: Through a systematic literature search-up to March 2016, we identified 9 observational studies (1,599,453 individuals, 5705 HCC-related deaths) reporting the association between premorbid body mass index (BMI), and HCC-related mortality. We estimated summary adjusted hazard ratio (aHR) with 95% confidence intervals (CIs), comparing obese (BMI>30 kg/m2) and overweight (BMI, 25 to 29.9 kg/m2) individuals with normal BMI individuals using random-effects model.

Results: On meta-analysis, compared with individuals with normal BMI, obese (aHR, 1.95; 95% CI, 1.46-2.46), but not overweight individuals (aHR, 1.08; 95% CI, 0.97-1.21), had higher HCC-related mortality, with moderate heterogeneity. On subgroup analysis, magnitude of increased mortality was higher in obese men (aHR, 2.50; 95% CI, 2.02-3.09; 3 studies) as compared with obese women (aHR, 1.45; 95% CI, 1.08-1.97; 2 studies). The impact of premorbid obesity on HCC-related mortality was observed only in western populations (aHR, 2.10; 95% CI, 1.77-2.48; 4 studies), but not Asian populations (aHR, 1.10; 95% CI, 0.63-1.92; 1 study). There was limited assessment of competing risk because of advanced liver disease.

Conclusions: On the basis of this meta-analysis, premorbid obesity may be independently associated with a 2-fold risk of HCC-related mortality. This association was more pronounced in men and western populations. Strategies targeting obesity-associated metabolic abnormalities may provide novel pathways for HCC therapy.

*Department of Internal Medicine

Division of Hematology Oncology, University of Texas Southwestern Medical Center

§University of Texas Southwestern Medical Center Library, Dallas, TX

Division of Cardiology, Massachusetts General Hospital, Boston, MA

Department of Surgical Sciences, University of Minnesota, Minneapolis, MN

Division of Hematology/Oncology, Springfield Clinic, Springfield, IL

#Division of Gastroenterology, University of California San Diego, La Jolla, CA

A.G. and A.D. contributed equally.

Paper presented in abstract form at the Gastrointestinal Cancers Symposium, held in San Francisco, CA in January 2017.

S.S. is partly supported by the National Library of Medicine/NIH training grant T15LM011271, and the American College of Gastroenterology Junior Faculty Development Award. The remaining authors declare that they have nothing to disclose.

Reprints: Siddharth Singh, MD, MS, Medicine, Division of Gastroenterology, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093. E-mail: sis040@ucsd.edu

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