We appreciate the thoughtful comments of Qing Pang and colleagues, who made an important point related to the association between obesity and prognosis for hepatocellular carcinoma (HCC).

In our study, we did not observe a significant impact of obesity in early adulthood, measured according to body mass index (BMI), on overall survival in patients with HCC.1 In support of our finding, a recent cohort study did not demonstrate a significant association between BMI at early adulthood and cancer mortality.2 In that study, the estimated adjusted hazard ratio and 95% confidence interval for the association of being overweight and obese with cancer mortality were 1.06 (0.93-1.21) and 1.12 (0.92-1.36), respectively.

We agree with Pang and colleagues that waist circumference, waist-hip ratio, and visceral fat may be good discriminators for central obesity and significant predictors of the morbidity or mortality of some diseases. However, we believe that determining the association between central obesity and HCC prognosis can be subject to bias for three reasons: (1) Chemotherapy confounding: Studies demonstrated that after cisplatin-based chemotherapy, patients may experience changes in serum lipids, with increased visceral fat volumes, visceral/subcutaneous fat ratios, and low-density lipoprotein and total cholesterol levels.3, 4 Given that the majority of HCC patients are diagnosed with advanced-stage disease that is treated with chemotherapy, and that cisplatin is an important chemotherapeutic agent for HCC,5 adjusting for the confounding effect of chemotherapy-induced visceral adiposity may be difficult. (2) Misclassification in anthropometric measurements of central obesity: Baseline assessment of the waist circumference or waist-hip ratio at the time of HCC diagnosis is subject to overestimation owing to decompensated cirrhosis and the presence of ascites. More than 60% of HCC patients had underlying cirrhosis; restricting the analysis to HCC patients without cirrhosis may lead to selection bias. (3) Multifactorial origin of HCC: Interestingly, each of the major risk factors for HCC, such as hepatitis C or B virus infection, alcohol consumption, obesity, and diabetes mellitus, are significantly associated with visceral adiposity.6 This may raise the question of whether the observed poor prognosis for HCC is attributable to risk factors per se or to their consequence of visceral adiposity. For example, hepatitis C virus infection is a significant predictor of HCC mortality, which at the same time explains more than 50% of the underlying visceral adiposity in HCC patients.6

Finally, large studies indicated that waist circumference and visceral fat measurement using computed tomography was not significantly better than BMI measurement in predicting nonalcoholic fatty liver diseases7 or diabetes.8

In summary, because of the complexity of the exposure (obesity), the multifactorial origin of HCC, and underlying chronic liver diseases in HCC patients, the independent role of general or central obesity on overall survival in HCC patients should be interpreted with caution.