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

Aliment Pharmacol Ther. 2014 May;39(10):1204-12. doi: 10.1111/apt.12731. Epub 2014 Mar 29.

Abstract

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)D3 ) levels were determined. 25(OH)D3 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)D3 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)D3 concentration was 17 ± 13 ng/mL with a range of 1-72 ng/mL. 25(OH)D3 serum levels negatively correlated with the stage of cirrhosis as well as with stages of HCC. Patients with severe 25(OH)D3 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)D3 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)D3 deficiency is associated with advanced stages of hepatocellular carcinoma and it is a prognostic indicator for a poor outcome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Calcifediol / blood*
  • Carcinoma, Hepatocellular / pathology*
  • Cohort Studies
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Liver Cirrhosis / complications
  • Liver Neoplasms / pathology*
  • Liver Transplantation / statistics & numerical data
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Prospective Studies
  • Severity of Illness Index
  • Vitamin D Deficiency / complications*
  • Vitamin D Deficiency / epidemiology
  • alpha-Fetoproteins / metabolism

Substances

  • alpha-Fetoproteins
  • Calcifediol