Obesity Early in Adulthood Increases Risk but Does Not Affect Outcomes of Hepatocellular Carcinoma

Abstract

Background & aims: Despite the significant association between obesity and several cancers, it has been difficult to establish an association between obesity and hepatocellular carcinoma (HCC). Patients with HCC often have ascites, making it a challenge to determine body mass index (BMI) accurately, and many factors contribute to the development of HCC. We performed a case-control study to investigate whether obesity early in adulthood affects risk, age of onset, or outcomes of patients with HCC.

Methods: We interviewed 622 patients newly diagnosed with HCC from January 2004 through December 2013, along with 660 healthy controls (frequency-matched by age and sex) to determine weights, heights, and body sizes (self-reported) at various ages before HCC development or enrollment as controls. Multivariable logistic and Cox regression analyses were performed to determine the independent effects of early obesity on risk for HCC and patient outcomes, respectively. BMI was calculated, and patients with a BMI of 30 kg/m(2) or greater were considered obese.

Results: Obesity in early adulthood (age, mid-20s to mid-40s) is a significant risk factor for HCC. The estimated odds ratios were 2.6 (95% confidence interval [CI], 1.4-4.4), 2.3 (95% CI, 1.2-4.4), and 3.6 (95% CI, 1.5-8.9) for the entire population, for men, and for women, respectively. Each unit increase in BMI at early adulthood was associated with a 3.89-month decrease in age at HCC diagnosis (P < .001). Moreover, there was a synergistic interaction between obesity and hepatitis virus infection. However, we found no effect of obesity on the overall survival of patients with HCC.

Conclusions: Early adulthood obesity is associated with an increased risk of developing HCC at a young age in the absence of major HCC risk factors, with no effect on outcomes of patients with HCC.

Keywords: Case-Control; HCC; Obesity; Risk Factor.

Figure 1

(A) Frequency of overweight and obesity at various ages during the life cycle before hepatocellular carcinoma diagnosis or control recruitment. (B) Distribution of body mass index status by percentages (overweight, obese) by HCC risk factors in cases and controls in their mid-20s to mid-40s.

Figure 2

(A) Odds Ratio, 95% Confidence Interval for the association between adulthood overweight (mid-20s to mid-40s) with hepatocellular carcinoma risk in the absence of major risk factors and with adjustment of confounding factors. (B) Odds Ratio, 95% Confidence Interval for the association between adulthood obesity (mid-20s to mid-40s) with hepatocellular carcinoma risk in the absence of major risk factors and with adjustment of confounding factors. Example: The estimated odds ratios, 95% confidence intervals for the association between adulthood overweight/obesity and HCC among non-diabetics were .9 (.6–1.4), P=.8 and 3.0 (1.5–5.8), P=.001 respectively, after adjustment for confounding factors including age, ethnicity, HCV, HBV, education level, alcohol drinking, cigarette smoking, physical activity, and family history of cancer.