title: Severe 25-hydroxyvitamin D deficiency identifies a poor prognosis in patients with hepatocellular carcinoma - a prospective cohort study.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Medizinische Klinik 1, Schwerpunkt Gastroenterologie und Hepatologie, Universitätsklinikum Frankfurt, Goethe-Universität, Frankfurt/Main, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Finkelmeier
authors.forename: B
authors.initials: B
authors.lastname: Kronenberger
authors.forename: V
authors.initials: V
authors.lastname: Köberle
authors.forename: J
authors.initials: J
authors.lastname: Bojunga
authors.forename: S
authors.initials: S
authors.lastname: Zeuzem
authors.forename: J
authors.initials: J
authors.lastname: Trojan
authors.forename: A
authors.initials: A
authors.lastname: Piiper
authors.forename: O
authors.initials: O
authors.lastname: Waidmann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002112:Calcifediol / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications; D008113:Liver Neoplasms / Q000473:pathology*; D016031:Liver Transplantation / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D012720:Severity of Illness Index; D014808:Vitamin D Deficiency / Q000150:complications* / Q000453:epidemiology; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D000509:alpha-Fetoproteins; D002112:Calcifediol