Letter to the Editor: Serum bioavailable 25‐hydroxyvitamin D levels correlate with hepatocellular carcinoma survival

FUNDING INFORMATIONSupported by the Zhejiang Provincial Natural Science Foundation of China (No. LGF19H290004). To the editor, It was with great interest that we read the article by Fang et al.[1] In this study, the researchers investigated the relationship between total, free, and bioavailable serum 25‐hydroxyvitamin D (25‐OHD) levels and survival in a large, prospective cohort of patients with HCC. The results showed that higher serum 25‐OHD levels were significantly and independently associated with increased survival in the HCC cohort, but neither total nor free serum 25‐OHD was associated with survival. This is an intriguing study with important clinical value, and we appreciate the efforts of the researchers. However, several concerns deserve to be discussed. First, ultraviolet (UV) light from sunlight is known to convert 7‐dehydrocholesterol in the skin into vitamin D3 (cholecalciferol), which is the main way to obtain endogenous vitamin D in humans.[2,3] In addition to the production of vitamin D in the body from UV radiation, vitamin D in food is also an important source, and the amount of vitamin D in different types of food varies.[4] When the level of vitamin D in the body increases, the level of 25‐OHD, which is converted in the liver through hydroxylation, increases accordingly.[5] Therefore, the duration of sunlight exposure and dietary structure (type and amount of food) should be considered as important confounding factors affecting the prognosis of HCC. Second, although the researchers showed that elevated serum bioavailable 25‐OHD was independently associated with a good prognosis in HCC patients, its predictive performance for HCC prognosis was not investigated. Therefore, we suggest that the researchers obtain the AUC by receiver operator characteristic curve analysis or calculate Harrell's concordance index (C‐index) to assess the predictive power of bioavailable 25‐OHD for HCC prognosis. Finally, we also suggest that the researchers use decision curve analysis to obtain the net benefit of prognostic indicators to assess the clinical utility of bioavailability 25‐OHD. CONFLICT OF INTEREST None to report. AUTHOR CONTRIBUTIONS Lu‐Lu Zhai, Shi‐Hui Zhen, and Zhi‐Gang Tang designed the study and wrote and reviewed the manuscript.