Severe 25‐hydroxyvitamin D deficiency identifies a poor prognosis in patients with hepatocellular carcinoma – a prospective cohort study

Summary Background Vitamin D is involved in many biological processes. The role of vitamin D in patients with hepatocellular carcinoma ( HCC ) remains inconclusive, although there is evolving evidence that vitamin D may modulate cancer development and progression. Aim To evaluate serum vitamin D as prognostic parameter in HCC , we performed a prospective cohort study. Methods HCC patients were prospectively recruited and 25‐hydroxyvitamin D3 (25( OH )D 3 ) levels were determined. 25( OH )D 3 levels were compared to stages of cirrhosis and HCC stages with nonparametric Kruskal–Wallis tests and Spearman correlations in 200 HCC patients. The association of the 25( OH )D 3 levels and overall survival ( OS ) was assessed in uni‐ and multivariate Cox regression models. Results Two‐hundred patients with HCC were included. The mean follow‐up time was 322 ± 342 days with a range of 1–1508 days. Nineteen patients underwent liver transplantation and 60 patients died within the observation time. The mean serum 25( OH )D 3 concentration was 17 ± 13 ng/mL with a range of 1–72 ng/mL. 25( OH )D 3 serum levels negatively correlated with the stage of cirrhosis as well as with stages of HCC . Patients with severe 25( OH )D 3 deficiency had the highest mortality risk (hazard ratio 2.225, 95% confidence interval 1.331–3.719, P = 0.002). Furthermore, very low 25( OH )D 3 levels were associated with mortality independently from the MELD score and high alpha‐Fetoprotein levels (>400 ng/mL) in a multivariate Cox regression model. Conclusions We conclude that 25( OH )D 3 deficiency is associated with advanced stages of hepatocellular carcinoma and it is a prognostic indicator for a poor outcome.