Vitamin D-related immunomodulation in patients with liver cirrhosis

Abstract

Objective(s) Increasing evidence indicates that vitamin D status is linked to severity of liver cirrhosis and patients’ survival. However, the potential role of vitamin D-related immunomodulation in hepatic decompensation and patients’ mortality in relation to vitamin D deficiency remains unknown. The aim of the current study is to evaluate the association between vitamin D status and vitamin D binding protein (VDBP) levels with serum cytokine and lipopolysaccharide binding protein (LBP) and to examine their role on disease severity and cirrhotics’ mortality. Methods One hundred consecutive Caucasian patients with liver cirrhosis were enrolled in the study. 25(OH)D, VDBP, and LBP concentrations were assessed by ELISA. Cytokine tumor necrosis factor-a (TNF-a), interleukin 6 (IL-6), IL-1β, IL-8, IL-10, and IL-12 levels were determined by Cytometric Bead Array. Results 25(OH)D levels were inversely correlated with CP score, MELD, IL-6, and CP stage and VDBP levels with CP score, MELD, IL-6, IL-8, LBP, and CP stage. Cirrhotics with 25(OH)D deficiency and severe deficiency had significantly higher CP score, increased IL-6 levels and lower VDBP levels. In the multivariate analysis, the independent prognostic factors associated with patients’ survival were CP stage B [hazard ratio = 6.75; 95% confidence interval (CI) 1.32, 34.43; P = 0.022], CP stage C (hazard ratio = 7.39; 95% CI 1.41, 38.81; P = 0.018), the presence of hepatocellular carcinoma (hazard ratio = 4.50; 95% CI 1.54, 13.13; P = 0.006) and 25(OH)D levels (hazard ratio = 0.87; 95% CI 0.80, 0.95; P = 0.002). Conclusion The results show that vitamin D status and VDBP levels are associated with liver cirrhosis severity and patients’ mortality, possibly through a proinflammatory immune response.

Vitamin A levels reflect disease severity and portal hypertension in patients with cirrhosis

“…VitD Def was highly common in our study cohort, being present in 57% of patients and additional 26% with VitD insufficiency, according to commonly used cut-offs for 25-OH-vitamin D levels [ 10 ]. Of note, comparisons to other studies regarding the prevalence of VitD Def are difficult to draw, as there are considerable differences in cut-offs and patient characteristics, however, other studies have demonstrated similar results [ 11 , 12 ]. As indicated previously, a recent meta-analysis confirmed the association between VitD deficiency and mortality in patients with cirrhosis [ 13 ].…”

“…Alcohol-related liver disease (ALD; n = 96, 41%) and viral hepatitis (n = 47, 20%) represented the predominant ACLD etiologies. Median HVPG was 18 (12)(13)(14)(15)(16)(17)(18)(19)(20) mmHg, and 202 (86%) patients had clinically significant portal hypertension (CSPH, i.e. an HVPG ≥ 10 mmHg).…”

“…Importantly, a previous study on patients with cirrhosis displayed a link between severe vitamin D deficiency (VitD Def ) and increased levels of inflammatory biomarkers as well as the risk of hepatic decompensation [ 11 ]. Similarly, disease severity and mortality were associated with VitD Def [ 12 , 13 ].…”

Indoleamine 2,3-dioxygenase 1 limits hepatic inflammatory cells recruitment and promotes bile duct ligation-induced liver fibrosis

“…Increasing pieces of evidences indicated that the pathogenesis of liver fibrosis related to the changes in immune function 9,10,35 . It is no doubt that the immunologic reactions response to hepatic fibrosis are complicated and incompletely clarified.…”

“…Recently, the abnormal changes of hepatic immune microenvironment during hepatic fibrosis attracted increasing attention among foreign and domestic scholars [7][8][9][10] . Indoleamine 2,3-dioxygenase 1 (IDO1), which serves as an immunomodulatory molecule, is an intracellular enzyme that participates in the metabolism of the essential amino acid tryptophan (TRP) in the kynurenine (KYN) pathway [11][12][13] .…”