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Udomsinprasert W, Jittikoon J. Vitamin D and liver fibrosis: Molecular mechanisms and clinical studies. Biomed Pharmacother 2018; 109:1351-1360. [PMID: 30551386 DOI: 10.1016/j.biopha.2018.10.140] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Revised: 10/22/2018] [Accepted: 10/24/2018] [Indexed: 12/21/2022] Open
Abstract
Vitamin D plays a primary role in regulation of bone metabolism and calcium homeostasis. Interestingly, emerging evidence suggests protective effects of vitamin D against liver fibrogenesis. However, the precise mechanisms of this action remain mysterious. Herein, this review aimed to summarize the role of vitamin D in liver fibrosis pathology and to update the current comprehensive knowledge regarding the clinical utility of vitamin D-based treatment in liver fibrosis. In regard to its effect on liver fibrosis, vitamin D possesses an anti-fibrotic effect on hepatic stellate cells via vitamin D receptor-mediated specific signal transduction pathways, which in turn inhibit expression of pro-fibrogenic genes. Furthermore, several studies demonstrated a significant association between low vitamin D levels and an increased risk of liver fibrosis. Additionally, high prevalence of vitamin D deficiency was noted in patients with liver fibrosis, suggesting the use of vitamin D status as a biochemical marker reflecting the progression of liver fibrosis. It is therefore reasonable to postulate that vitamin D supplementation being a cost effective and relative simple procedure may benefit to liver fibrosis. Nevertheless, further research is needed to fully elucidate its regulatory role in inhibiting liver fibrogenesis and to estimate the safety and efficiency of vitamin D supplementation as a relatively inexpensive treatment for liver fibrosis in patients with chronic liver diseases.
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Affiliation(s)
- Wanvisa Udomsinprasert
- Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.
| | - Jiraphun Jittikoon
- Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.
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Abstract
In the past few years, a growing body of clinical evidence has highlighted the risk of vitamin D deficiency in patients with chronic hepatitis C and that vitamin D levels are associated with the course of hepatitis C virus (HCV) infection, adverse effects, and treatment response to peginterferon/ribavirin. Recently, studies have found that vitamin D status is related to drug resistance and increased risk of infection in patients with liver cirrhosis. Vitamin D-related gene polymorphisms have been found to explain the interactions between vitamin D deficiency and HCV infection, offering a new perspective toward understanding the current problems such as the development of insulin resistance and racial differences in sustained virological response. Studies have been conducted to determine whether vitamin D supplementation as an adjuvant yields a better result compared with traditional HCV treatment. Here, we provide a brief review of the past and present knowledge of vitamin D in HCV infection.
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Scalioni LDP, dos Santos BR, Spritzer PM, Villela-Nogueira CA, Laura Lewis-Ximenez L, Pollo-Flores P, Bordalo Cathalá Esberard E, Brandão-Mello CE, Lampe E, Villar LM. Impact of vitamin D receptor and binding protein gene polymorphisms in clinical and laboratory data of HCV patients: Cross sectional study. Medicine (Baltimore) 2018; 97:e9881. [PMID: 29465575 PMCID: PMC5842007 DOI: 10.1097/md.0000000000009881] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Potential relationship of vitamin D, vitamin D receptor (VDR), and vitamin D binding protein (DBP) have been suggested in the pathophysiology of hepatitis C virus (HCV) infection. The aim of this observational study is to determine vitamin D levels, and VDR and DBP genetic polymorphism according demographic and laboratory data in chronic HCV patients (CHC).A total of 148 CHC patients gave serum samples for testing 25-hydroxyvitamin D (25 (OH)D) level by immunochemiluminometric assay (<20 ng/mL defined as deficient) and donated blood samples to allelic discrimination analysis using TaqMan assays. Analyzed single nucleotide polymorphisms (SNPs) were: VDR-rs7975232 (ApaI) C>A, rs731236 A>G (TaqI), rs1544410 C>T (BsmI), rs10735810 T>C (FokI) and carrier globulin/binding protein (GC)-rs4588 and rs7041 and the haplotype bAt [CCA]. Hepatic fibrosis was assessed using Fib-4 and Forns index.Eighty-two (54.40%) patients demonstrated deficiency of vitamin D and this was associated to AST (P = .019 [CI: 1.003-1.034]), total cholesterol (P = .038 [CI: 1.004-1.164]), fibrosis grade (P < .001 [CI: 0.000-0.844]), and FokI (P = .028) allele T presence. Association was found between VDR polymorphism and fibrosis (BsmI andTaqI), triglycerides (TaqI), and HDL (FokI). DBP polymorphism was associated to HCV genotype (GC rs7041), previous HCV treatment, and GGT (GC rs4588).In conclusion, low frequency of vitamin D deficiency was found, but VDR polymorphisms were frequently associated to fibrosis grade suggesting that they could be used as disease evaluation markers to understand the mechanisms underlying the virus-host interaction.
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Affiliation(s)
| | - Betânia Rodrigues dos Santos
- Gynecological Endocrinology Unit Division of Endocrinology Porto Alegre Clinical Hospital, Department of Physiology Federal University of Rio Grande do Sul
| | - Poli Mara Spritzer
- Gynecological Endocrinology Unit Division of Endocrinology Porto Alegre Clinical Hospital, Department of Physiology Federal University of Rio Grande do Sul
| | | | | | | | | | | | - Elisabeth Lampe
- Laboratory of Viral Hepatitis, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro
| | - Livia Melo Villar
- Laboratory of Viral Hepatitis, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro
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Jha AK, Jha SK, Kumar A, Dayal VM, Jha SK. Effect of replenishment of vitamin D on survival in patients with decompensated liver cirrhosis: A prospective study. World J Gastrointest Pathophysiol 2017; 8:133-141. [PMID: 28868183 PMCID: PMC5561434 DOI: 10.4291/wjgp.v8.i3.133] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2016] [Revised: 01/01/2017] [Accepted: 06/08/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To assess the vitamin D (VD) deficiency as a prognostic factor and effect of replenishment of VD on mortality in decompensated cirrhosis.
METHODS Patients with decompensated liver cirrhosis were screened for serum VD levels. A total of 101 VD deficient patients (< 20 ng/mL) were randomly enrolled in two groups: Treatment group (n = 51) and control group (n = 50). Treatment group received VD treatment in the form of intramuscular cholecalciferol 300000 IU as loading dose and 800 IU/d oral as maintenance dose along with 1000 mg oral calcium supplementation. The VD level, clinical parameters and survival of both the groups were compared for 6-mo.
RESULTS Prevalence of vitamin D deficiency (VDD) in decompensated CLD was 84.31%. The mean (SD) age of the patients in the treatment group (M:F: 40:11) and control group (M:F: 37:13) were 46.2 (± 14.93) years and 43.28 (± 12.53) years, respectively. Baseline mean (CI) VD (ng/mL) in control group and treatment group were 9.15 (8.35-9.94) and 9.65 (8.63-10.7), respectively. Mean (CI) serum VD level (ng/mL) at 6-mo in control group and treatment group were 9.02 (6.88-11.17) and 29 (23-35), respectively. Over the period of time the VD, calcium and phosphorus level was improved in treatment group compared to control group. There was non-significant trend seen in greater survival (69% vs 64%; P > 0.05) and longer survival (155 d vs 141 d; P > 0.05) in treatment group compared to control group. VD level had no significant association with mortality (P > 0.05). In multivariate analysis, treatment with VD supplement was found significantly (P < 0.05; adjusted hazard ratio: 0.48) associated with survival of the patients over 6-mo.
CONCLUSION VD deficiency is very common in patients of decompensated CLD. Replenishment of VD may improve survival in patients with decompensated liver cirrhosis.
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Milovanović OZ. Vitamin D Deficiency and its Importance - A Global Problem of Today, Realistic or Not? SERBIAN JOURNAL OF EXPERIMENTAL AND CLINICAL RESEARCH 2017. [DOI: 10.1515/sjecr-2016-0045] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Abstract
Vitamin D, also known as the “sun vitamin” in the literature, has been examined for many years and still arouses researchers’ interest due to the pleiotropic effects achieved in the human body. Because of the influence on mineral homeostasis, the initially observed effects of vitamin D on the prevention and treatment of rickets, have now been extended to a large number of diseases with different aetiologies such as cardiovascular, autoimmune, endocrine, infectious, neurological, malignant and other diseases. Due to the large number of experimental studies in animals and humans, we have exact information about the role of vitamin D in many of these conditions. Reaching an adequate level of 25(OH)D in the human body is a basic requirement for the realization of these effects; 25(OH)D is a metabolic product that reflects the vitamin D status but that does not have any biological activity. The biological activities of vitamin D can occur only after the formation of a second metabolic product, 1,25(OH)2D, in the kidneys. The three main sources of acquiring vitamin D are through food, skin and supplementation. Food is not a rich source of vitamin D; it is clear that the most important influences to achieve an optimal vitamin D status in the human body are vitamin D synthesis at the skin and adequate supplementation intake. An alarming fact is that vitamin D deficiency is detected in an increasing number of people from one day to another in the general world population and that this condition has pandemic dimensions. Introducing the beneficial effects and sources of vitamin D to the general population and to medical experts with adequate supplementation regime can decrease the number of people who are vitamin D deficient.
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Dadabhai AS, Saberi B, Lobner K, Shinohara RT, Mullin GE. Influence of vitamin D on liver fibrosis in chronic hepatitis C: A systematic review and meta-analysis of the pooled clinical trials data. World J Hepatol 2017; 9:278-287. [PMID: 28261385 PMCID: PMC5316848 DOI: 10.4254/wjh.v9.i5.278] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2016] [Revised: 12/14/2016] [Accepted: 01/02/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the relationship between vitamin D and liver fibrosis in hepatitis C-monoinfected or hepatitis C virus (HCV)-human immunodeficiency virus (HIV) co-infected patients. METHODS Pertinent studies were located by a library literature search in PubMed/Embase/Cochrane/Scopus/LILACS by two individual reviewers. Inclusion criteria: (1) studies with patients with HCV or co-infected HCV/HIV; (2) studies with patients ≥ 18 years old; (3) studies that evaluated liver fibrosis stage, only based on liver biopsy; and (4) studies that reported serum or plasma 25(OH)D levels. Studies that included pediatric patients, other etiologies of liver disease, or did not use liver biopsy for fibrosis evaluation, or studies with inadequate data were excluded. Estimated measures of association reported in the literature, as well as corresponding measures of uncertainty, were recorded and corresponding odds ratios with 95%CI were included in a meta-analysis. RESULTS The pooled data of this systematic review showed that 9 of the 12 studies correlated advanced liver disease defined as a Metavir value of F3/4 with 25(OH) D level insufficiency. The meta-analysis indicated a significant association across studies. CONCLUSION Low vitamin D status is common in chronic Hepatitis C patients and is associated with advanced liver fibrosis.
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Affiliation(s)
- Alia S Dadabhai
- Alia S Dadabhai, Behnam Saberi, Katie Lobner, Gerard E Mullin, Division of Gastroenterology and Hepatology, the Johns Hopkins University School of Medicine, Baltimore, MD 21224, United States
| | - Behnam Saberi
- Alia S Dadabhai, Behnam Saberi, Katie Lobner, Gerard E Mullin, Division of Gastroenterology and Hepatology, the Johns Hopkins University School of Medicine, Baltimore, MD 21224, United States
| | - Katie Lobner
- Alia S Dadabhai, Behnam Saberi, Katie Lobner, Gerard E Mullin, Division of Gastroenterology and Hepatology, the Johns Hopkins University School of Medicine, Baltimore, MD 21224, United States
| | - Russell T Shinohara
- Alia S Dadabhai, Behnam Saberi, Katie Lobner, Gerard E Mullin, Division of Gastroenterology and Hepatology, the Johns Hopkins University School of Medicine, Baltimore, MD 21224, United States
| | - Gerard E Mullin
- Alia S Dadabhai, Behnam Saberi, Katie Lobner, Gerard E Mullin, Division of Gastroenterology and Hepatology, the Johns Hopkins University School of Medicine, Baltimore, MD 21224, United States
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Zhao XY, Li J, Wang JH, Habib S, Wei W, Sun SJ, Strobel HW, Jia JD. Vitamin D serum level is associated with Child-Pugh score and metabolic enzyme imbalances, but not viral load in chronic hepatitis B patients. Medicine (Baltimore) 2016; 95:e3926. [PMID: 27399065 PMCID: PMC5058794 DOI: 10.1097/md.0000000000003926] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Vitamin D deficiency is common in patients with chronic liver diseases. However, vitamin D status in persons with chronic hepatitis B virus (HBV) infection is not consistently reported. Specifically, the impact of liver dysfunction on vitamin D status has not been well addressed.We recruited a group of patients (n = 345) with chronic hepatitis B (n = 115), hepatitis B related cirrhosis (n = 115), and age- and gender-matched healthy controls (n = 115). Serum 25-hydroxyvitamin D3 [25(OH)D3], its related metabolic enzymes, intact parathyroid hormone were measured. Calcium, magnesium, and phosphorus were obtained from medical record.Serum 25(OH)D3 levels in chronic hepatitis B patients (7.83 ± 3.47 ng/mL) were significantly lower than that in healthy controls (9.76 ± 4.36 ng/mL, P < 0.001), but significantly higher than that in hepatitis B-related cirrhotic patients (5.21 ± 3.67 ng/mL, P < 0.001). Furthermore, 25(OH)D3 decreased stepwise with higher Child-Pugh classification. However, there were no significant differences in 25(OH)D3 levels between (1) hepatitis B e antigen (HBeAg +) and HBeAg(-) persons, or (2) among persons with different HBV viral load, or (3) between treatment naïve and patients on antiviral therapy. Multiple logistic regression analyses confirmed that higher Child-Pugh score was independently associated with 25(OH)D3 deficiency (<10 ng/mL) with an odds ratio of 1.20 (confidence interval 1.03-1.39, P = 0.016). Levels of cytochrome P450 (CYP) 27A1 were significantly decreased, whereas levels of CYP24A1 were significantly elevated in cirrhotic patients.These results suggest that decreasing vitamin D levels are likely to be a result, rather than a cause, of liver dysfunction and irrespective of HBV viral load. Reduction in 25(OH)D3 levels is possibly due to downregulation of the synthetic hydroxylase CYP27A1 and concurrent upregulation of degrading CYP24A1 in patients with liver cirrhosis.
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Affiliation(s)
- Xin-yan Zhao
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory on Translational Medicine on Cirrhosis, National Clinical Research Center for Digestive Diseases, Beijing
| | - Jia Li
- Tianjin Institute of Hepatology, Tianjin Second People's Hospital, Tianjin
| | - Jing-han Wang
- Clinical Laboratory, the Second Hospital of Dalian Medical University, Dalian, Liaoning
| | - Sohail Habib
- International School, Capital Medical University, Beijing, People's Republic of China
| | - Wei Wei
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory on Translational Medicine on Cirrhosis, National Clinical Research Center for Digestive Diseases, Beijing
| | - Shu-jie Sun
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory on Translational Medicine on Cirrhosis, National Clinical Research Center for Digestive Diseases, Beijing
| | - Henry W. Strobel
- Department of Biochemistry & Molecular Biology, University of Texas Medical School, Houston, TX
| | - Ji-dong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory on Translational Medicine on Cirrhosis, National Clinical Research Center for Digestive Diseases, Beijing
- Correspondence: Ji-dong Jia, Liver Research Center, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong-An Road, Xicheng District, Beijing 100050, People's Republic of China (e-mail: )
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Gabr SA, Alghadir AH, Allam AA, Ajarem J, Al-Basher G, Abdel-Maksoud MA, Ghfar AA, Aboud A. Correlation between vitamin D levels and apoptosis in geriatric patients infected with hepatitis C virus genotype 4. Clin Interv Aging 2016; 11:523-33. [PMID: 27217734 PMCID: PMC4862759 DOI: 10.2147/cia.s104599] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Background Vitamin D levels play a pivotal role in most biological processes and differ according to age. A deficiency of vitamin D in chronic hepatitis C (CHC) patients has been shown to be linked with the severity of liver fibrosis, but little is known about the mechanism of this association. Objective In this study, we evaluate the potential interrelation between vitamin D levels, oxidative stress, and apoptosis, based on liver fibrosis in geriatric patients infected with hepatitis C virus (HCV) genotype 4. Subjects and methods A total of 120 adult individuals aged 30–68 years were recruited in this study. Of these, 20 healthy subjects (15 men and five women) with a mean age of 48.3±6.1 years were selected as controls, and 100 patients with a mean age of 47.8±4.9 years with chronic HCV (CHC) who had undergone liver biopsy (80 men and 20 women) were included in this study. Based on liver radiographic (computed tomography, magnetic resonance imaging) and histological Metavir system analyses, the CHC patients were classified into three groups: asymptomatic CHC carriers (n=30), fibrosis (n=25), and cirrhosis (n=45). HCV RNA, HCV genotypes, inflammatory cytokines AFP and TNFα, 25-hydroxyvitamin D (25[OH]D) levels, apoptotic markers single-stranded DNA (ssDNA) and soluble Fas (sFas), and oxidative stress markers nitric oxide (NO) and total antioxidant capacity (TAC) were estimated by using molecular, immunoassay, and colorimetric techniques. Results Approximately 30% of the study population (n=30) were diagnosed as asymptomatic CHC carriers, and 70% of the study population (n=70) had severe fibrosis; these were classified into fibrosis and cirrhosis. There was a significant reduction in 25(OH)D levels and TAC activity, along with an increase in levels of NO, AFP, TNFα, ssDNA, and sFas in fibrosis and cirrhosis subjects compared with those of asymptomatic CHC carriers and health controls. The deficiency in 25(OH)D levels correlated positively with sFas, ssDNA, AFP, TNFα, NO, and TAC, and negatively with age, sex, liver function, body mass index, homeostatic model assessment – insulin resistance, HCV RNA, and viral load. Significant intercorrelation was reported between serum 25(OH)D concentrations and apoptotic and oxidative markers, which suggested progression of liver pathogenesis and fibrogenesis via oxidative and apoptotic mechanisms. Conclusion The data showed that vitamin D status was significantly correlated with pathogenesis and fibrogenesis of the liver in geriatric patients infected with HCV genotype 4. The deficiency in 25(OH)D levels was shown to have a pivotal role in the pathogenesis of liver via apoptotic, oxidative stress, and inflammatory mechanistic pathways. The data point to adequate vitamin D levels being recommended for a good response to treatment strategies, especially in older CHC patients.
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Affiliation(s)
- Sami A Gabr
- Rehabilitation Research Chair, College of Applied Medical Sciences, King Saud University, Riyadh, Kingdom of Saudi Arabia; Department of Anatomy, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Ahmad H Alghadir
- Rehabilitation Research Chair, College of Applied Medical Sciences, King Saud University, Riyadh, Kingdom of Saudi Arabia
| | - Ahmed A Allam
- Zoology Department, College of Science, King Saud University, Riyadh, Saudi Arabia; Zoology Department, Faculty of Science, Beni-Suef University, Beni Suef, Egypt
| | - Jamaan Ajarem
- Zoology Department, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Ghada Al-Basher
- Zoology Department, College of Science, King Saud University, Riyadh, Saudi Arabia
| | | | - Ayman A Ghfar
- Department of Chemistry, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Alaa Aboud
- Internal Endemic Medicine Department, College of Medicine, Beni-Suef University, Beni Suef, Egypt
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Zhang C, Zhao L, Ding Y, Sheng Q, Bai H, An Z, Xia T, Wang J, Dou X. Enhanced LL-37 expression following vitamin D supplementation in patients with cirrhosis and spontaneous bacterial peritonitis. Liver Int 2016; 36:68-75. [PMID: 26058412 DOI: 10.1111/liv.12888] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2015] [Accepted: 06/04/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS The morbidity and mortality of spontaneous bacterial peritonitis (SBP) are high among patients with cirrhosis; however, the mechanisms of SBP pathogenesis are poorly understood. This study aimed to determine the role of the vitamin D-LL-37 pathway in the pathogenesis and treatment in patients with cirrhosis and SBP. METHODS Serum 25-hydroxyvitamin D concentrations of 119 patients with chronic liver diseases were tested. Vitamin D receptor (VDR) and LL-37 in peritoneal leucocytes of cirrhotic and ascitic patients with SBP were detected and compared with those without SBP. Then the peritoneal macrophages of non-infected patients were cultured and activated by lipopolysaccharide (LPS) to analyse the changes of VDR and LL-37 expressions after incubation with vitamin D. RESULTS Vitamin D deficiency or insufficiency was found in all of patients with cirrhosis. LPS inhibited VDR and LL-37 expression in peritoneal macrophages [1.3-fold decrease (P = 0.003) and 20-fold decrease (P = 0.010) respectively]. However, vitamin D could reverse the inhibition of both VDR and LL-37 [1.5-fold increase (P = 0.001) and 2000-fold increase (P < 0.001) respectively]. The effect of the incubation time following vitamin D supplementation was significant for LL-37 expression, with a peak expression found at 36 h (P < 0.001). CONCLUSIONS When vitamin D levels were low, bacteria inhibited VDR and LL-37 responses in peritoneal macrophages as a mechanism to evade antibacterial defence. Vitamin D supplementation could up-regulate peritoneal macrophage VDR and LL-37 expressions, which resulted in an enhanced immunological defence against SBP in patients with cirrhosis and ascites.
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Affiliation(s)
- Chong Zhang
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, China
| | - Lianrong Zhao
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yang Ding
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, China
| | - Qiuju Sheng
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, China
| | - Han Bai
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, China
| | - Ziying An
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, China
| | - Tingting Xia
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, China
| | - Jingyan Wang
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xiaoguang Dou
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, China
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Ren Y, Liu M, Zhao J, Ren F, Chen Y, Li JF, Zhang JY, Qu F, Zhang JL, Duan ZP, Zheng SJ. Serum vitamin D 3 does not correlate with liver fibrosis in chronic hepatitis C. World J Gastroenterol 2015; 21:11152-11159. [PMID: 26494969 PMCID: PMC4607912 DOI: 10.3748/wjg.v21.i39.11152] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2015] [Revised: 07/02/2015] [Accepted: 09/02/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the relationship between serum vitamin D3 levels and liver fibrosis or inflammation in treatment-naive Chinese patients with chronic hepatitis C (CHC).
METHODS: From July 2010 to June 2011, we enrolled 122 CHC patients and 11 healthy controls from Dingxi city, Gansu Province, China. The patients were infected with Hepatitis C virus (HCV) during blood cell re-transfusion following plasma donation in 1992-1995, and had never received antiviral treatment. At present, all the patients except two underwent liver biopsy with ultrasound guidance. The Scheuer Scoring System was used to evaluate hepatic inflammation and the Metavir Scoring System was used to evaluate hepatic fibrosis. Twelve-hour overnight fasting blood samples were collected in the morning of the day of biopsy. Serum levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, cholinesterase, prothrombin activity, albumin, γ-glutamyl transpeptidase, hemoglobin, calcium and phosphorus were determined. Serum HCV RNA levels were measured by real-time PCR. Serum levels of 25-hydroxyvitamin D3 [25(OH)D3] and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] were measured by high-performance liquid chromatography tandem mass spectrometry.
RESULTS: Serum levels of 25(OH)D3 but not 24,25(OH)2D3 were significantly lower in CHC patients than in control subjects. Serum 25(OH)D3 levels did not correlate with liver fibrosis, inflammation, patient age, or levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, prothrombin activity, cholinesterase or HCV RNA. However, serum 25(OH)D3 levels did correlate with serum 24,25(OH)2D3 levels. Serum 25(OH)D3 and 24,25(OH)2D3 levels, and the 25(OH)D3/24,25(OH)2D3 ratio, have no difference among the fibrosis stages or inflammation grades.
CONCLUSION: We found that serum levels of 25(OH)D3 and its degradation metabolite 24,25(OH)2D3 did not correlate with liver fibrosis in treatment-naive Chinese patient with CHC.
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Sarkar S, Hewison M, Studzinski GP, Li YC, Kalia V. Role of vitamin D in cytotoxic T lymphocyte immunity to pathogens and cancer. Crit Rev Clin Lab Sci 2015; 53:132-45. [PMID: 26479950 DOI: 10.3109/10408363.2015.1094443] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The discovery of vitamin D receptor (VDR) expression in immune cells has opened up a new area of research into immunoregulation by vitamin D, a niche that is distinct from its classical role in skeletal health. Today, about three decades since this discovery, numerous cellular and molecular targets of vitamin D in the immune system have been delineated. Moreover, strong clinical associations between vitamin D status and the incidence/severity of many immune-regulated disorders (e.g. infectious diseases, cancers and autoimmunity) have prompted the idea of using vitamin D supplementation to manipulate disease outcome. While much is known about the effects of vitamin D on innate immune responses and helper T (T(H)) cell immunity, there has been relatively limited progress on the frontier of cytotoxic T lymphocyte (CTL) immunity--an arm of host cellular adaptive immunity that is crucial for the control of such intracellular pathogens as human immunodeficiency virus (HIV), tuberculosis (TB), malaria, and hepatitis C virus (HCV). In this review, we discuss the strong historical and clinical link between vitamin D and infectious diseases that involves cytotoxic T lymphocyte (CTL) immunity, present our current understanding as well as critical knowledge gaps in the realm of vitamin D regulation of host CTL responses, and highlight potential regulatory connections between vitamin D and effector and memory CD8 T cell differentiation events during infections.
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Affiliation(s)
- Surojit Sarkar
- a Department of Pediatrics, Division of Hematology and Oncology , University of Washington School of Medicine , Seattle , WA , USA .,b Seattle Children's Research Institute, Ben Towne Center for Childhood Cancer Research , Seattle , WA , USA
| | - Martin Hewison
- c Centre for Endocrinology, Diabetes and Metabolism (CEDAM), The University of Birmingham , Birmingham , UK
| | - George P Studzinski
- d Department of Pathology and Laboratory Medicine , Rutgers New Jersey Medical School , Newark , NJ , USA , and
| | - Yan Chun Li
- e Department of Medicine, Division of Biological Sciences , The University of Chicago , Chicago , IL , USA
| | - Vandana Kalia
- a Department of Pediatrics, Division of Hematology and Oncology , University of Washington School of Medicine , Seattle , WA , USA .,b Seattle Children's Research Institute, Ben Towne Center for Childhood Cancer Research , Seattle , WA , USA
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The prevalence and severity of 25-(OH)-vitamin D insufficiency in HCV infected and in HBV infected patients: a prospective study. Clin Exp Hepatol 2015; 1:5-11. [PMID: 28856249 PMCID: PMC5421164 DOI: 10.5114/ceh.2015.51373] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2015] [Accepted: 04/13/2015] [Indexed: 01/29/2023] Open
Abstract
AIM OF THE STUDY To assess the prevalence and severity of vitamin D insufficiency in patients with hepatitis C virus (HCV) infection and in patients with hepatitis B virus (HBV) infection. MATERIAL AND METHODS This prospective study included 90 patients with chronic hepatitis C and 35 patients with chronic hepatitis B admitted to the Infectious Diseases Department between March 2013 and May 2014. Patients with chronic liver disease other than viral hepatitis, HIV co-infection, advanced liver disease and a history of diseases influencing vitamin D status were excluded. Serum vitamin D measurement as well as liver function, viral load, HCV genotype, interleukin 28 and liver fibrosis assessments were performed. RESULTS In all patients, the mean vitamin D serum concentration was 18.8 (± 8.9) ng/ml. The mean vitamin D level in HBV infected patients was lower than in HCV infected patients (17.6 ng/ml vs. 19.3 ng/ml; p = 0.43). Vitamin D status was assessed in relation to viral load, HCV genotype, interleukin 28 and sex, but the differences were not significant. In both groups, serum vitamin D levels were significantly lower in winter compared to summer (14.2 ng/ml vs. 23.9 ng/ml in patients infected with HCV [p < 0.000001] and 14.7 ng/ml vs. 23.8 ng/ml in patients infected with HBV [p < 0.001]). CONCLUSIONS Our study showed that in patients with chronic hepatitis C or chronic hepatitis B, insufficient 25(OH)D concentrations occur very often, but are not associated with poor virological characteristics. The only factor influencing the vitamin D level was the season.
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