Research ArticleMarked 25-hydroxyvitamin D deficiency is associated with poor prognosis in patients with alcoholic liver disease

Background & AimsVitamin D deficiency has been frequently reported in advanced liver disease. However, its influence on alcoholic liver disease (ALD) has been poorly elucidated. We investigated the association of vitamin D with clinical, biological, and histological parameters and survival in ALD patients. Furthermore, we explored the effect of vitamin D treatment on ALD patient peripheral blood mononuclear cells (PBMCs), and in a murine experimental model of ALD.MethodsSerum levels of 25-hydroxyvitamin D [25(OH)D] were determined in 324 Caucasian ALD patients and 201 healthy controls. In vitro experiments on vitamin D pre-treated PBMCs evaluated TNFα production by ELISA in culture supernatants. Mice were submitted to an ethanol-fed diet and some of them were orally supplemented three times per week with 1,25(OH)2D.ResultsSevere deficiency in 25(OH)D (<10 ng/ml) was significantly associated with higher aspartate aminotransferase levels (p = 1.00 × 10−3), increased hepatic venous pressure gradient (p = 5.80 × 10−6), MELD (p = 2.50 × 10−4), and Child-Pugh scores (p = 8.50 × 10−7). Furthermore, in multivariable analysis, a low 25(OH)D concentration was associated with cirrhosis (OR = 2.13, 95% CI = 1.18-3.84, p = 0.013) and mortality (HR = 4.33, 95% CI = 1.47-12.78, p = 7.94 × 10−3) at one year. In addition, in vitro, 1,25(OH)2D pretreatment decreased TNFα production by stimulated PBMCs of ALD patients (p = 3.00 × 10−3), while in vivo, it decreased hepatic TNFα expression in ethanol-fed mice (p = 0.04).ConclusionsLow 25(OH)D levels are associated with increased liver damage and mortality in ALD. Our results suggest that vitamin D might be both a biomarker of severity and a potential therapeutic target in ALD.