25-hydroxyvitamin D deficiency is associated with infections and mortality in cirrhosis

Objective: Vitamin D is involved in many biological functions such as proliferation, apoptosis, cellular signaling and anti-inflammation. Recently, an increased incidence of 25(OH)D3 deficiency has been found in subjects suffering from chronic liver diseases and the extent of 25(OH)D3 deficiency in the patients correlated with the severity of liver dysfunction. We hypothesized that low vitamin D levels might be associated with inflammatory responses and infectious complications in cirrhotic patients. Therefore, we performed a prospective cohort study investigating the relation of 25(OH)D3 levels with stages of cirrhosis and mortality as well as the association of 25(OH)D3 concentrations and complications of cirrhosis including infectious complications.

Methods: From May 2009 to July 2011, 270 patients with cirrhosis presenting at the Department of Internal Medicine 1 of the Frankfurt University Hospital outpatient clinic were consecutively enrolled into the present prospective cohort study. Patient characteristics, treatment and outcome were entered into a prospectively conducted database. 25-hydroxyvitamin (25(OH)D3) levels were quantified by radioimmunoassay from serum samples obtained at the day of study inclusion. Patients were followed until death or last contact. The primary end point was overall survival (OS).

Results: The mean follow-up time was 422 +/- 399 days with a range of 1 – 1382 days. 37 (13.7%) patients underwent liver transplantation and were excluded from further analysis from the day of transplantation. 85 (31.5%) individuals died within the study. The mean serum 25(OH)D3 concentration was 9.3 ± 7.5 ng/ml with a range of 0.9 to 46.1 ng/ml. 180 (66.7%) patients had very low 25(OH)D3 levels (< 10 ng/ml) and were classified as insufficient, 66 (24.4%) patients had low levels (10 – 20 ng/ml) and were classified as deficient. 24 (8.9%) patients had normal 25(OH)D3 levels (> 20 ng/ml). 25(OH)D3 levels differed significantly between Child Pugh stages and showed a negative correlation with the MELD score. Patients with decompensated cirrhosis had significantly lowered 25(OH)D3 levels. 25(OH)D3 levels significantly differed between patients with infectious complications compared to those without infections and individuals with SBP (spontaneous bacterial peritonitis) had significantly lower 25(OH)D3 levels compared to patients without SBP. Patients with low serum vitamin D had a significantly higher risk for occurrence of MDR (multi-drug resistant) bacteria (HR 2.36). 25(OH)D3 levels ≤ 6 ng/ml as well as serum 25(OH)D3 concentrations ≤ 10 ng/ml levels were associated with higher mortality compared to higher 25(OH)D3 levels (HR 1.82 for 6 ng/ml and HR 1.71 for 10 ng/ml, respectively). In a multivariate Cox regression model 25(OH)D3 levels were independently associated with mortality.

Conclusion: We conclude, that 25(OH)D3 deficiency is associated with advanced liver disease and it is a prognostic indicator for a poor outcome. Furthermore low vitamin D levels are associated with infectious complications. In conclusion our work adds further evidence that vitamin D might be a factor influencing the prognosis of cirrhotics.

Corresponding author: Finkelmeier, Fabian

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