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      Low 25-Hydroxyvitamin D Levels Are Associated with Infections and Mortality in Patients with Cirrhosis

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          Abstract

          Background & Aims

          Vitamin D, best known to regulate bone mineralization, has numerous additional roles including regulation inflammatory pathways. Recently, an increased incidence of 25-hydroxyvitamin D3 (25(OH)D 3) deficiency has been found in subjects suffering from liver diseases. We here investigated if low vitamin D levels might be associated with prognosis, inflammation and infectious complications in patients with cirrhosis.

          Methods

          We performed a prospective cohort study investigating the relation between 25(OH)D 3 levels and stages of cirrhosis, mortality and complications of cirrhosis, including infections.

          Results

          251 patients with cirrhosis were enrolled into the present prospective cohort study. 25(OH)D 3 levels were quantified by radioimmunoassay from serum samples obtained at study inclusion. The mean follow-up time was 411 ± 397 days with a range of 1-1382 days. 30 (12.0%) patients underwent liver transplantation and 85 (33.8%) individuals died within the study. The mean serum 25(OH)D 3 concentration was 8.93 ± 7.1 ng/ml with a range of 1.0 to 46.0 ng/ml. 25(OH)D 3 levels differed significantly between Child Pugh scores and showed a negative correlation with the model of end stage liver disease (MELD) score. Patients with decompensated cirrhosis and infectious complications, had significantly lower 25(OH)D 3 levels compared to subjects without complications. Low 25(OH)D 3 was associated with mortality in uni- as well as multivariate Cox regression models.

          Conclusions

          25(OH)D 3 deficiency is associated with advanced liver disease and low 25(OH)D 3 levels are an indicator for a poor outcome and are associated with infectious complications.

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          Most cited references24

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          Decoding cell death signals in liver inflammation.

          Inflammation can be either beneficial or detrimental to the liver, depending on multiple factors. Mild (i.e., limited in intensity and destined to resolve) inflammatory responses have indeed been shown to exert consistent hepatoprotective effects, contributing to tissue repair and promoting the re-establishment of homeostasis. Conversely, excessive (i.e., disproportionate in intensity and permanent) inflammation may induce a massive loss of hepatocytes and hence exacerbate the severity of various hepatic conditions, including ischemia-reperfusion injury, systemic metabolic alterations (e.g., obesity, diabetes, non-alcoholic fatty liver disorders), alcoholic hepatitis, intoxication by xenobiotics and infection, de facto being associated with irreversible liver damage, fibrosis, and carcinogenesis. Both liver-resident cells (e.g., Kupffer cells, hepatic stellate cells, sinusoidal endothelial cells) and cells that are recruited in response to injury (e.g., monocytes, macrophages, dendritic cells, natural killer cells) emit pro-inflammatory signals including - but not limited to - cytokines, chemokines, lipid messengers, and reactive oxygen species that contribute to the apoptotic or necrotic demise of hepatocytes. In turn, dying hepatocytes release damage-associated molecular patterns that-upon binding to evolutionary conserved pattern recognition receptors-activate cells of the innate immune system to further stimulate inflammatory responses, hence establishing a highly hepatotoxic feedforward cycle of inflammation and cell death. In this review, we discuss the cellular and molecular mechanisms that account for the most deleterious effect of hepatic inflammation at the cellular level, that is, the initiation of a massive cell death response among hepatocytes. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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            Surgery and portal hypertension.

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              Clinical practice. Vitamin D insufficiency.

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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                29 June 2015
                2015
                : 10
                : 6
                : e0132119
                Affiliations
                [001]Medizinische Klinik 1, Schwerpunkt Gastroenterologie und Hepatologie, Universitätsklinikum Frankfurt, Goethe-Universität, Theodor-Stern-Kai 7, D-60590 Frankfurt/Main, Germany
                University of Navarra School of Medicine and Center for Applied Medical Research (CIMA), SPAIN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: FF BK AP OW. Performed the experiments: FF. Analyzed the data: FF BK AP OW. Wrote the paper: FF BK SZ AP OW.

                Article
                PONE-D-15-17636
                10.1371/journal.pone.0132119
                4487892
                26121590
                5e5ea0cb-94bf-4b19-8bd8-8f5e38316d8f
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 23 April 2015
                : 10 June 2015
                Page count
                Figures: 3, Tables: 2, Pages: 12
                Funding
                This work was supported by grants from the foundation Dr. Paul und Ursula Klein and the foundation Marie Christine Held and Erika Hecker to Oliver Waidmann and the Scolari Foundation to Bernd Kronenberger. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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