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Dyson JK. Editorial: Autoimmune Hepatitis-Could It Be as Easy as Vitamin D? Aliment Pharmacol Ther 2025; 61:1065-1066. [PMID: 39891362 DOI: 10.1111/apt.18524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Revised: 01/18/2025] [Accepted: 01/18/2025] [Indexed: 02/03/2025]
Affiliation(s)
- Jessica K Dyson
- Liver Unit, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
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Romeo M, Dallio M, Cipullo M, Coppola A, Mazzarella C, Mammone S, Iadanza G, Napolitano C, Vaia P, Ventriglia L, Federico A. Nutritional and Psychological Support as a Multidisciplinary Coordinated Approach in the Management of Chronic Liver Disease: A Scoping Review. Nutr Rev 2025:nuaf001. [PMID: 39992295 DOI: 10.1093/nutrit/nuaf001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/25/2025] Open
Abstract
OBJECTIVES This review emphasizes a novel, multidisciplinary, coordinated approach in the management of chronic liver diseases (CLDs). BACKGROUND Chronic liver diseases represent a significant global health burden, marked by a notable shift in the prevalence patterns from virus-related to metabolic and alcohol-related entities. Malnutrition, frailty, and sarcopenia exert a substantial impact on patients with cirrhosis, affecting 75%-90% of cases and escalating as the disease progresses. The European Association for the Study of the Liver recommends a comprehensive approach to nutritional care, emphasizing the need for detailed assessments in patients with cirrhosis, using diverse tools such as computed tomography scans, bioelectrical impedance analysis, and evaluations of muscle function. Considering the prevalence of nutritional and psychological disorders in the CLD population, the treatment of these patients should be founded indispensably on a multidisciplinary approach. METHODS A systematic search was conducted of the PubMed, MEDLINE, and SCOPUS databases to identify trials investigating the health effects of nutritional and psychological assessments in patients with CLD. RESULTS In dealing with the treatment of patients with CLD, an exploration of the psychological domain emerges as crucial, because psychological distress, especially depression, exerts a tangible influence on patient outcomes. Thus, the engagement of psychologists and/or psychotherapists, who might use techniques such as cognitive behavioral therapy, could enhance patients' comprehension of nutritional implications in their treatment and make them more aware of their illness. CONCLUSION The review emphasizes the relevance of both nutritional and psychological assessments in patients with CLD that could improve patient education on the pivotal role of nutrition in disease management. Randomized controlled trials evaluating the combined impact of nutritional and psychological support are recommended to further investigate this complex clinical landscape.
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Affiliation(s)
- Mario Romeo
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples 80138, Italy
| | - Marcello Dallio
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples 80138, Italy
| | - Marina Cipullo
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples 80138, Italy
| | - Annachiara Coppola
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples 80138, Italy
| | - Chiara Mazzarella
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples 80138, Italy
| | - Simone Mammone
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples 80138, Italy
| | - Giorgia Iadanza
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples 80138, Italy
| | - Carmine Napolitano
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples 80138, Italy
| | - Paolo Vaia
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples 80138, Italy
| | - Lorenzo Ventriglia
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples 80138, Italy
| | - Alessandro Federico
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania "Luigi Vanvitelli," Naples 80138, Italy
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Kilani Y, Alsakarneh S, Madi MY, Mosquera DAG, Ferreira MN, Jaber F, Helzberg J, Duong N, Syn WK. Autoimmune Hepatitis and Vitamin D Deficiency: A Nationwide Perspective. Aliment Pharmacol Ther 2025; 61:682-692. [PMID: 39660607 DOI: 10.1111/apt.18438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Revised: 08/15/2024] [Accepted: 12/01/2024] [Indexed: 12/12/2024]
Abstract
BACKGROUND Vitamin D deficiency is linked to worse outcomes in patients with chronic liver diseases (CLD). However, data in patients with autoimmune hepatitis (AIH) remain limited. AIMS We aimed to assess the impact of vitamin D deficiency on the outcomes of individuals with AIH. METHODS This retrospective cohort study used the TriNetX research network to identify patients with AIH. Patients were matched using propensity score matching and stratified to sufficient vitamin D levels (e.g., 25 (OH) D3 ≥ 30 ng/mL), vitamin D insufficiency (25 (OH) D3: 20-29.9 ng/mL) and vitamin D deficiency (e.g., 25 (OH) D3 < 20 ng/mL). The primary outcome was the all-cause mortality among adult patients with AIH. Secondary outcomes included decompensated liver cirrhosis, acute hepatic failure, liver transplantation (LT), all-cause hospitalizations and all-cause critical care admissions. RESULTS A total of 1288 AIH patients with vitamin D deficiency were identified and propensity matched with 1288 patients with normal vitamin D levels. Patients with vitamin D deficiency had significantly increased odds for all-cause mortality compared to those with normal levels (adjusted odds ratio (aOR) = 3.2, 95%CI: 2.3-4.48). Patients with vitamin D deficiency were at increased odds of all-cause hospitalizations (aOR = 2.37, 95%CI: 1.97-2.84), critical care unit admissions (aOR = 2.8, 95%CI: 2.21-3.71), decompensated liver cirrhosis (aOR = 2.74, 95%CI: 2.13-3.54), acute hepatic failure (aOR = 3.11, 95%CI: 2.09-4.62) and LT (aOR = 3.47, 95%CI: 1.71-7.04), as compared to those with normal vitamin D levels. CONCLUSION This cohort study showed significantly increased odds for all-cause mortality in AIH patients with vitamin D deficiency. Vitamin D deficiency in patients with AIH was associated with increased likelihood of hospitalisation, decompensated liver cirrhosis, acute liver failure and LT.
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Affiliation(s)
- Yassine Kilani
- Department of Medicine, NYC Health + Hospitals, Lincoln - Weill Cornell Medical College Affiliate, New York, New York, USA
| | - Saqr Alsakarneh
- Department of Medicine, University of Missouri-Kansas City, Kansas City, Missouri, USA
| | - Mahmoud Y Madi
- Division of Gastroenterology & Hepatology, Department of Medicine, Saint Louis University, St. Louis, Missouri, USA
| | | | - Mariana Nunes Ferreira
- Department of Medicine, NYC Health + Hospitals, Lincoln - Weill Cornell Medical College Affiliate, New York, New York, USA
| | - Fouad Jaber
- Department of Medicine, University of Missouri-Kansas City, Kansas City, Missouri, USA
| | - John Helzberg
- Department of Gastroenterology & Hepatology, University of Missouri-Kansas City, Missouri, USA
| | - Nikki Duong
- Department of Gastroenterology and Hepatology, Stanford University, Stanford, Palo Alto, USA
| | - Wing-Kin Syn
- Division of Gastroenterology & Hepatology, Department of Medicine, Saint Louis University, St. Louis, Missouri, USA
- Department of Physiology, Faculty of Medicine and Nursing, University of Basque Country UPV/EHU, Vizcaya, Spain
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Mihele AI, Hocopan SC, Matei SD, Brata RD, Trifan DF, Lazăr L, Ghitea TC. Exploring the Correlation Between Vitamin D Levels and Serological Markers in Liver Diseases: Insights from a Cross-Sectional Study. In Vivo 2024; 38:2271-2283. [PMID: 39187343 PMCID: PMC11363789 DOI: 10.21873/invivo.13692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Revised: 05/20/2024] [Accepted: 05/23/2024] [Indexed: 08/28/2024]
Abstract
BACKGROUND/AIM This study investigated the correlation between vitamin D levels and serological markers of liver diseases in two groups of patients: the control group (CG) and the study group (SG). MATERIALS AND METHODS The study analyzed data on vitamin D levels categorized as insufficient, sufficient, and optimal, along with serological markers, such as alpha2-macroglobulin, haptoglobin, apolipoprotein A1, bilirubin total, gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose, total cholesterol, and triglycerides. RESULTS The results indicate significant differences in vitamin D levels between the two groups, particularly in SG, where vitamin D levels varied according to its status and correlated with serological markers. Marker levels, including alpha2-macroglobulin, glucose, and total cholesterol, were notably higher in SG compared to CG, suggesting a potential association with non-alcoholic fatty liver disease (NAFLD). Further analysis using Pearson correlation revealed a strong, inverse relationship between vitamin D levels and FibroTest, NashTest, alpha2-globulin, and glucose. Additionally, increasing FibroTest and NashTest stages, as well as levels of alpha2-macroglobulin and glucose, were associated with lower vitamin D levels in SG. CONCLUSION These findings under-score the complex interplay between vitamin D and serological markers in NAFLD, highlighting the potential significance of vitamin D levels in disease progression. Further research is warranted to elucidate the mechanisms underlying this relationship and its clinical implications.
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Affiliation(s)
- Adina Ioana Mihele
- Doctoral School of Biological and Biomedical Sciences, University of Oradea, Oradea, Romania
| | - Sergiu Cristian Hocopan
- Medicine Department, Faculty of Medicine and Pharmacy, University of Oradea, Oradea, Romania
| | - Sergiu Dorin Matei
- Medicine Department, Faculty of Medicine and Pharmacy, University of Oradea, Oradea, Romania
| | - Roxana Daniela Brata
- Medicine Department, Faculty of Medicine and Pharmacy, University of Oradea, Oradea, Romania
| | - Daniela Florina Trifan
- Doctoral School of Biological and Biomedical Sciences, University of Oradea, Oradea, Romania
| | - Liviu Lazăr
- Medicine Department, Faculty of Medicine and Pharmacy, University of Oradea, Oradea, Romania
| | - Timea Claudia Ghitea
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, Oradea, Romania
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Ioniuc I, Lupu A, Tarnita I, Mastaleru A, Trandafir LM, Lupu VV, Starcea IM, Alecsa M, Morariu ID, Salaru DL, Azoicai A. Insights into the Management of Chronic Hepatitis in Children-From Oxidative Stress to Antioxidant Therapy. Int J Mol Sci 2024; 25:3908. [PMID: 38612717 PMCID: PMC11011982 DOI: 10.3390/ijms25073908] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 03/22/2024] [Accepted: 03/29/2024] [Indexed: 04/14/2024] Open
Abstract
Recent research has generated awareness of the existence of various pathophysiological pathways that contribute to the development of chronic diseases; thus, pro-oxidative factors have been accepted as significant contributors to the emergence of a wide range of diseases, from inflammatory to malignant. Redox homeostasis is especially crucial in liver pathology, as disturbances at this level have been linked to a variety of chronic diseases. Hepatitis is an umbrella term used to describe liver inflammation, which is the foundation of this disease regardless of its cause. Chronic hepatitis produces both oxidative stress generated by hepatocyte inflammation and viral inoculation. The majority of hepatitis in children is caused by a virus, and current studies reveal that 60-80% of cases become chronic, with many young patients still at risk of advancing liver damage. This review intends to emphasize the relevance of understanding these pathological redox pathways, as well as the need to update therapeutic strategies in chronic liver pathology, considering the beneficial effects of antioxidants.
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Affiliation(s)
- Ileana Ioniuc
- Department of Mother and Child, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (I.I.); (I.T.); (L.M.T.); (I.M.S.); (M.A.); (A.A.)
| | - Ancuta Lupu
- Department of Mother and Child, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (I.I.); (I.T.); (L.M.T.); (I.M.S.); (M.A.); (A.A.)
| | - Irina Tarnita
- Department of Mother and Child, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (I.I.); (I.T.); (L.M.T.); (I.M.S.); (M.A.); (A.A.)
| | - Alexandra Mastaleru
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (A.M.); (D.L.S.)
| | - Laura Mihaela Trandafir
- Department of Mother and Child, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (I.I.); (I.T.); (L.M.T.); (I.M.S.); (M.A.); (A.A.)
| | - Vasile Valeriu Lupu
- Department of Mother and Child, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (I.I.); (I.T.); (L.M.T.); (I.M.S.); (M.A.); (A.A.)
| | - Iuliana Magdalena Starcea
- Department of Mother and Child, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (I.I.); (I.T.); (L.M.T.); (I.M.S.); (M.A.); (A.A.)
| | - Mirabela Alecsa
- Department of Mother and Child, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (I.I.); (I.T.); (L.M.T.); (I.M.S.); (M.A.); (A.A.)
| | - Ionela Daniela Morariu
- Faculty of Pharmacy, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania;
| | - Delia Lidia Salaru
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (A.M.); (D.L.S.)
| | - Alice Azoicai
- Department of Mother and Child, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (I.I.); (I.T.); (L.M.T.); (I.M.S.); (M.A.); (A.A.)
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Yang K, Pan Y, Zhang H, Jin L, Wang X. Hepatic vitamin D receptor expression is negatively associated with liver inflammation and fibrosis in patients with chronic HBV infection. Clin Exp Med 2023; 23:2151-2158. [PMID: 36289101 DOI: 10.1007/s10238-022-00919-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 10/11/2022] [Indexed: 11/25/2022]
Abstract
The vitamin D receptor (VDR) is a nuclear transcription factor that acts as the main transducer in response to vitamin D (VD), regulating about 3% of the gene expression in the human genome. This study investigated the expression of VDR in the liver of patients with chronic hepatitis B virus (HBV) infection and determined its correlation with liver inflammation and fibrosis. We evaluated the effects of HBV infection on the expression of VDR in vivo and in vitro and further investigate the potential mechanism. Subsequently, the associations between hepatic VDR expression with liver inflammation and fibrosis were statistically analyzed. Results showed that hepatic VDR expression was significantly decreased in patients with chronic HBV infection as compared to healthy individuals. Similarly, in vitro experiments further confirmed that HBV infection could inhibit the expression of VDR in hepatocytes. Mechanistically, HBV was able to directly induce the expression of miR-125a which inhibited the mRNA and protein levels of VDR. Statistical analysis showed that hepatic VDR expression was significantly negatively correlated with liver inflammation and fibrosis in patients. We conclude that inhibition of hepatic vitamin D receptor expression by HBV/miR-125a is negatively associated with liver inflammation and fibrosis in patients with chronic HBV infection.
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Affiliation(s)
- Kai Yang
- Department of Medical Technology, Anhui Medical College, Hefei, 230601, Anhui, China.
| | - Ying Pan
- Department of Medical Technology, Anhui Medical College, Hefei, 230601, Anhui, China
| | - Hao Zhang
- Department of Clinical Laboratory, The Second Hospital of Anhui Medical University, Hefei, 230601, Anhui, China
| | - Lei Jin
- Department of Infectious Disease, The Second Hospital of Anhui Medical University, Hefei, 230601, Anhui, China
| | - Xian Wang
- Department of Pathology, The Second Hospital of Anhui Medical University, Hefei, 230601, Anhui, China
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Wang R, Zhu X, Zhang X, Liu H, Ji YL, Chen YH. Association of vitamin D and polymorphisms of its receptor with antiviral therapy in pregnant women with hepatitis B. World J Gastroenterol 2023; 29:3003-3012. [PMID: 37274802 PMCID: PMC10237097 DOI: 10.3748/wjg.v29.i19.3003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 03/28/2023] [Accepted: 04/24/2023] [Indexed: 05/16/2023] Open
Abstract
BACKGROUND The interruption of mother-to-child transmission (MTCT) is considered important to decrease the individual and population morbidity of hepatitis B virus (HBV) infection as well as the global burden of hepatitis B. Serum vitamin D (VD) is associated with hepatitis B. AIM To assess whether baseline VD levels and single nucleotide polymorphisms of the VD receptor gene (VDR SNPs) are associated with the efficacy of tenofovir disoproxil fumarate (TDF) in the prevention of MTCT in pregnant women with high HBV viral loads. METHODS Thirty-eight pregnant women who were at high risk for MTCT of HBV (those with an HBV DNA level ≥ 2 × 105 IU/mL during 12-24 wk of gestation) receiving antiviral therapy of TDF between June 1, 2019 and June 30, 2021 in Mianyang were included in this retrospective study. The women received 300 mg TDF once daily from gestational weeks 24-28 until 3 mo after delivery. To further characterize the clinical relevance of maternal serum HBV DNA levels, we stratified patients according to HBV DNA level as follows: Those with levels < 2 × 105 (full responder group) vs those levels ≥ 2 × 105 IU/mL (partial responder group) at delivery. Serum levels of 25-hydroxyvitamin D [25(OH)D], liver function markers, virological parameters, VDR SNPs and other clinical parameters were collected to analyze their association with the efficacy of TDF. The Mann-Whitney U test or t test was used to analyze the serum levels of 25(OH)D in different groups. Multiple linear regressions were utilized to analyze the determinants of the maternal HBV DNA level at delivery. Univariate and multivariate logistic regression analyses were employed to explore the association of targeted antiviral effects with various characteristics at baseline and delivery. RESULTS A total of 38 pregnant women in Mianyang City at high risk for MTCT of HBV were enrolled in the study. The MTCT rate was 0%. No mother achieved hepatitis B e antigen or hepatitis B surface antigen (HBsAg) clearance at delivery. Twenty-three (60.5%) participants were full responders, and 15 (39.5%) participants were partial responders according to antiviral efficacy. The present study showed that a high percentage (76.3%) of pregnant women with high HBV viral loads had deficient (< 20 ng/mL) or insufficient (≥ 20 but < 31 ng/mL) VD levels. Serum 25(OH)D levels in partial responders appeared to be significantly lower than those in full responders both at baseline (25.44 ± 9.42 vs 17.66 ± 5.34 ng/mL, P = 0.006) and delivery (26.76 ± 8.59 vs 21.24 ± 6.88 ng/mL, P = 0.044). Serum 25(OH)D levels were negatively correlated with maternal HBV DNA levels [log(10) IU/mL] at delivery after TDF therapy (r = -0.345, P = 0.034). In a multiple linear regression analysis, maternal HBV DNA levels were associated with baseline maternal serum 25(OH)D levels (P < 0.0001, β = -0.446), BMI (P = 0.03, β = -0.245), baseline maternal log10 HBsAg levels (P = 0.05, β = 0.285) and cholesterol levels at delivery (P = 0.015, β = 0.341). Multivariate logistic regression analysis showed that baseline serum 25(OH)D levels (OR = 1.23, 95%CI: 1.04-1.44), maternal VDR Cdx2 TT (OR = 0.09, 95%CI: 0.01-0.88) and cholesterol levels at delivery (OR = 0.39, 95%CI: 0.17-0.87) were associated with targeted antiviral effects (maternal HBV DNA levels < 2 × 105 at delivery). CONCLUSION Maternal VD levels and VDR SNPs may be associated with the efficacy of antiviral therapy in pregnant women with high HBV viral loads. Future studies to evaluate the therapeutic value of VD and its analogs in reducing the MTCT of HBV may be justified.
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Affiliation(s)
- Rui Wang
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xia Zhu
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xuan Zhang
- Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Huan Liu
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yu-Lin Ji
- Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yong-Hua Chen
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
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Ashique S, Gupta K, Gupta G, Mishra N, Singh S, Wadhwa S, Gulati M, Dureja H, Zacconi F, Oliver BG, Paudel KR, Hansbro PM, Chellappan DK, Dua K. Vitamin D-A prominent immunomodulator to prevent COVID-19 infection. Int J Rheum Dis 2023; 26:13-30. [PMID: 36308699 PMCID: PMC9874620 DOI: 10.1111/1756-185x.14477] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Revised: 09/15/2022] [Accepted: 10/07/2022] [Indexed: 01/27/2023]
Abstract
COVID-19 remains a life-threatening infectious disease worldwide. Several bio-active agents have been tested and evaluated in an effort to contain this disease. Unfortunately, none of the therapies have been successful, owing to their safety concerns and the presence of various adverse effects. Various countries have developed vaccines as a preventive measure; however, they have not been widely accepted as effective strategies. The virus has proven to be exceedingly contagious and lethal, so finding an effective treatment strategy has been a top priority in medical research. The significance of vitamin D in influencing many components of the innate and adaptive immune systems is examined in this study. This review aims to summarize the research on the use of vitamin D for COVID-19 treatment and prevention. Vitamin D supplementation has now become an efficient option to boost the immune response for all ages in preventing the spread of infection. Vitamin D is an immunomodulator that treats infected lung tissue by improving innate and adaptive immune responses and downregulating the inflammatory cascades. The preventive action exerted by vitamin D supplementation (at a specific dose) has been accepted by several observational research investigations and clinical trials on the avoidance of viral and acute respiratory dysfunctions. To assess the existing consensus about vitamin D supplementation as a strategy to treat and prevent the development and progression of COVID-19 disease, this review intends to synthesize the evidence around vitamin D in relation to COVID-19 infection.
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Affiliation(s)
- Sumel Ashique
- Department of PharmaceuticsBharat Institute of Technology (BIT), School of PharmacyMeerutIndia
| | - Kirti Gupta
- Department of Pharmacology, MM College of PharmacyMaharishi Markandeshwar (Deemed to be) UniversityAmbalaIndia
| | - Gaurav Gupta
- School of PharmacySuresh Gyan Vihar UniversityJaipurIndia
- Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical SciencesSaveetha UniversityChennaiIndia
- Uttaranchal Institute of Pharmaceutical SciencesUttaranchal UniversityDehradunIndia
| | - Neeraj Mishra
- Department of Pharmaceutics, Amity Institute of PharmacyAmity University Madhya Pradesh (AUMP)GwaliorIndia
| | - Sachin Kumar Singh
- School of Pharmaceutical SciencesLovely Professional UniversityJalandharIndia
- Faculty of Health, Australian Research Centre in Complementary and Integrative MedicineUniversity of Technology SydneyNew South WalesUltimoAustralia
| | - Sheetu Wadhwa
- School of Pharmaceutical SciencesLovely Professional UniversityJalandharIndia
| | - Monica Gulati
- School of Pharmaceutical SciencesLovely Professional UniversityJalandharIndia
| | - Harish Dureja
- Department of Pharmaceutical SciencesMaharshi Dayanand UniversityRohtakIndia
| | - Flavia Zacconi
- Facultad de Química y de FarmaciaPontificia Universidad Católica de ChileSantiagoChile
- Institute for Biological and Medical Engineering, Schools of Engineering, Medicine and Biological SciencesPontificia Universidad Católica de ChileSantiagoChile
| | - Brian G. Oliver
- Woolcock Institute of Medical ResearchUniversity of SydneyNew South WalesSydneyAustralia
- School of Life Sciences, Faculty of ScienceUniversity of Technology Sydney2007New South WalesSydneyAustralia
| | - Keshav Raj Paudel
- Centre for InflammationCentenary Institute and University of Technology Sydney, Faculty of Science, School of Life SciencesNew South WalesSydneyAustralia
| | - Philip M. Hansbro
- Centre for InflammationCentenary Institute and University of Technology Sydney, Faculty of Science, School of Life SciencesNew South WalesSydneyAustralia
| | - Dinesh Kumar Chellappan
- Department of Life Sciences, School of PharmacyInternational Medical UniversityKuala LumpurMalaysia
| | - Kamal Dua
- School of Life Sciences, Faculty of ScienceUniversity of Technology Sydney2007New South WalesSydneyAustralia
- Discipline of Pharmacy, Graduate School of HealthUniversity of Technology SydneyNew South WalesSydneyAustralia
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Pomacu MM, Trașcă DM, Pădureanu V, Stănciulescu EC, Busuioc CJ, Pisoschi CG, Bugă AM. Correlations of Serum Vitamin D Level with Markers of Oxidative Stress and Apoptosis in Liver Cirrhosis. CURRENT HEALTH SCIENCES JOURNAL 2023; 49:54-66. [PMID: 37780191 PMCID: PMC10541071 DOI: 10.12865/chsj.49.01.54] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Accepted: 02/25/2023] [Indexed: 10/03/2023]
Abstract
In this study we investigated the relationship between vitamin D and markers of oxidative stress and apoptosis in patients with liver cirrhosis stratified according serum GGT activity. Forty-eight patients with liver cirrhosis of various aetiology were selected, among which 58% cases (n=28) diagnosed with alcoholic liver cirrhosis and 42% (n=20) with cirrhosis after hepatitis virus infection. Each group was divided into three quartiles according GGT activity. 25-hydroxyvitamin D [25-(HO) vit D], markers of oxidative stress (catalase, superoxide dismutase) and apoptosis (M30) were compared. Higher levels of GGT were correlated with elevated AST, ALT and ALP values in both groups. A statistically significant difference was observed when comparing 25-(OH) vit D levels of patients suffering from ethanol-induced liver cirrhosis versus control group for all the quartiles as well as for those from the first quartile of viral-induced liver cirrhosis. For SOD, statistically significant differences were noticed between all cirrhosis subgroups and the control group. CAT values in all cirrhosis subgroups were lower than in control, but significant differences were only between Q2.2 and Q1.3 quartiles and Q2.2 and control. Correlation of 25-(OH) vit D versus SOD yields statistically significant results in ethanol-induced cirrhosis patients. M30 activity was increased in patients with alcoholic cirrhosis compared to controls and those with virus-induced cirrhosis, being correlated with the degree of GGT activity. Our results emphasized that vitamin D deficiency is associated with enhanced liver dysfunction regardless of the trigger responsible for disease onset. Furthermore, vitamin D deficiency augments liver injury by promoting oxidative stress which influence the survival mechanisms of parenchymal liver cells.
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Affiliation(s)
- Mihnea Marian Pomacu
- PhD Doctoral School, University of Medicine and Pharmacy of Craiova
- 4thDepartment of Medical Specialties, University of Medicine and Pharmacy of Craiova
- 1st Clinic of Internal Medicine, "Filantropia" Clinical City Hospital of Craiova
| | - Diana Maria Trașcă
- 4thDepartment of Medical Specialties, University of Medicine and Pharmacy of Craiova
- 1st Clinic of Internal Medicine, "Filantropia" Clinical City Hospital of Craiova
| | - Vlad Pădureanu
- 4thDepartment of Medical Specialties, University of Medicine and Pharmacy of Craiova
- 2nd Clinic of Internal Medicine, Emergency County Hospital of Craiova
| | | | | | | | - Ana Maria Bugă
- Department of Biochemistry, University of Medicine and Pharmacy of Craiova
- Regional Center for Medical Genetics Dolj, Emergency County Hospital of Craiova
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10
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Cao B, Wen T, Wei M, Xiong Y, Liu W, Zhu L, Zhou J. Transcriptomic analysis reveal the responses of dendritic cells to VDBP. Genes Genomics 2022; 44:1271-1282. [PMID: 35278207 DOI: 10.1007/s13258-022-01234-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Accepted: 02/19/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND Vitamin D binding protein (VDBP) is an essential plasma carrier protein, which plays possible roles in reproductive health, disease and so on. However, the effects of VDBP on immunity have not been fully studied and the pertinent literatures remain very limited. OBJECTIVE In this study, we introduced the exogenous VDBP into DC2.4 and established a stable DC2.4/VDBP cell line to explore the role of this gene in immunity. METHODS Dendritic cells (DCs), as the most effective antigen presenting cells (APC) found so far, are directly involved in regulating some innate immunity. In order to evaluate the biological role of VDBP in DCs, we stably overexpressed VDBP in DCs, and conducted Cell Counting Kit‑8 (CCK-8 kit) and flow cytometry to detect changes in cell function. CCK-8 kit was used to monitor the viability of DCs after gene overexpression, and flow cytometry was used to detect changes in cell cycle distribution and apoptosis. Subsequently, in order to reveal the mechanism of VDBP regulating DCs, we adopted RNA sequencing (RNA-seq). RESULTS CCK-8 results revealed VDBP successfully inhibited viability of DCs. Besides, we found that overexpression of this gene greatly promoted apoptosis and obviously altered the cell cycle distribution of DCs in G1 and G2 phases. Moreover, RNA-seq was carried out and 151 differently expression genes (DEGs) were obtained. In addition, gene differential expression analysis showed that most of them were uniformly enriched in immunity-related pathways. CONCLUSION These results indicated that VDBP greatly repressed proliferation, facilitated apoptosis and changed cell cycle in DCs via altering the expression levels of gene associated with their cellular immunity.
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Affiliation(s)
- Biwei Cao
- Department of Tuina and Rehabilitation Medicine, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, 430061, China
- Department of Tuina and Rehabilitation Medicine, Affiliated Hospital of Hubei University of Chinese Medicine, Wuhan, 430061, China
- Department of Tuina and Rehabilitation Medicine, Hubei Province Academy of Traditional Chinese Medicine, Wuhan, 430074, China
| | - Tao Wen
- Department of Tuina and Rehabilitation Medicine, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, 430061, China
- Department of Tuina and Rehabilitation Medicine, Affiliated Hospital of Hubei University of Chinese Medicine, Wuhan, 430061, China
- Department of Tuina and Rehabilitation Medicine, Hubei Province Academy of Traditional Chinese Medicine, Wuhan, 430074, China
| | - Meng Wei
- Department of Tuina and Rehabilitation Medicine, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, 430061, China
- Department of Tuina and Rehabilitation Medicine, Affiliated Hospital of Hubei University of Chinese Medicine, Wuhan, 430061, China
- Department of Tuina and Rehabilitation Medicine, Hubei Province Academy of Traditional Chinese Medicine, Wuhan, 430074, China
| | - Yuan Xiong
- Department of Tuina and Rehabilitation Medicine, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, 430061, China
- Department of Tuina and Rehabilitation Medicine, Affiliated Hospital of Hubei University of Chinese Medicine, Wuhan, 430061, China
- Department of Tuina and Rehabilitation Medicine, Hubei Province Academy of Traditional Chinese Medicine, Wuhan, 430074, China
| | - Wan Liu
- Department of Tuina and Rehabilitation Medicine, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, 430061, China
- Department of Tuina and Rehabilitation Medicine, Affiliated Hospital of Hubei University of Chinese Medicine, Wuhan, 430061, China
- Department of Tuina and Rehabilitation Medicine, Hubei Province Academy of Traditional Chinese Medicine, Wuhan, 430074, China
| | - Li Zhu
- Department of Tuina and Rehabilitation Medicine, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, 430061, China
- Department of Tuina and Rehabilitation Medicine, Affiliated Hospital of Hubei University of Chinese Medicine, Wuhan, 430061, China
- Department of Tuina and Rehabilitation Medicine, Hubei Province Academy of Traditional Chinese Medicine, Wuhan, 430074, China
| | - Jing Zhou
- First Clinical Medical College, Hubei University of Chinese Medicine, Wuhan, 430061, China.
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11
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Youssry S, Shalaby T, Maher AS, Ghoneim H. Association of hepatitis B vaccine response to vitamin D supplementation and ultraviolet B (UVB) exposure during different time intervals in experimental animals. Immunol Res 2022; 70:537-545. [PMID: 35585421 PMCID: PMC9273550 DOI: 10.1007/s12026-022-09287-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Accepted: 05/04/2022] [Indexed: 01/28/2023]
Abstract
The implications of vitamin D deficiency on the immune system have become clearer in recent years, being associated with less immune response following HBV vaccine. We aimed to elucidate the effect of vitamin D supplementation and UVB exposure on short- and long-term performance of hepatitis B vaccine. Forty-five male rabbits were randomly divided into 3 groups that were immunized with recombinant HBsAg. The first group (group I) represented a negative control group, whereas group III rabbits were administered with commercially available 1,25 (OH)2 vitamin D as an alternative for UVB exposure in group II. Results showed that vitamin D concentrations were significantly higher in UVB exposed group compared to both negative control and vitamin D-supplemented groups during short- and long-time intervals. In addition, means of anti-HBsAg isotypes’ levels and anti-HBsAg IgG avidity% were significantly higher in negative control group compared to other groups during short- and long-time intervals. Moreover, vitamin D serum concentration was positively correlated with anti-HBsAg IgG level and avidity % in both negative control and vitamin D-supplemented groups, while it was negatively correlated with anti-HBsAg IgM level in negative control group. It can be concluded from the above results that UVB radiation may have both augmenting and suppressive effects and that circulating serum vitamin D concentration may have a positive association with premium immune modulation following HBV vaccination.
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Affiliation(s)
- Sara Youssry
- Department of Immunology and Allergy, Medical Research Institute, Alexandria University, 165 El-Horreya Avenue, El Hadara, Alexandria, 21561, Egypt.
| | - Thanaa Shalaby
- Department of Medical Biophysics, Medical Research Institute, Alexandria University, 165 El-Horreya Avenue, El- Hadara, Alexandria, 21561, Egypt
| | | | - Hossam Ghoneim
- Department of Immunology and Allergy, Medical Research Institute, Alexandria University, 165 El-Horreya Avenue, El Hadara, Alexandria, 21561, Egypt
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12
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Markotić A, Kelava T, Markotić H, Silovski H, Mrzljak A. Vitamin D in liver cancer: novel insights and future perspectives. Croat Med J 2022; 63:187-196. [PMID: 35505652 PMCID: PMC9086812 DOI: 10.3325/cmj.2022.63.187] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Accepted: 02/09/2022] [Indexed: 11/17/2022] Open
Abstract
Vitamin D has been a focus of attention in liver cancer due to its direct and indirect antineoplastic effects. This review critically evaluates data from recently published basic and clinical studies investigating the role of vitamin D in liver cancer. Basic studies indicate that vitamin D plays an important role in liver cancer development by suppressing the activity of hepatic stellate cells and Kupffer cells. Furthermore, vitamin D has a direct anti-proliferative, anti-angiogenic, proapoptotic, and prodifferentiative effect on liver cancer cells. Recent investigation suggested several interesting mechanisms of these actions, such as inactivation of Notch signaling, p27 accumulation, and tyrosine-protein kinase Met/extracellular signal-regulated kinases inhibition. On the other hand, data from clinical observational studies, although promising, are still inconclusive. Unfortunately, studies on the effect of vitamin D supplementation were generally focused on short-term outcomes of chronic liver diseases (liver enzyme levels or elastographic finding); therefore, there are still no reliable data on the effect of vitamin D supplementation on liver cancer occurrence or survival.
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Affiliation(s)
| | - Tomislav Kelava
- Tomislav Kelava, Department of Physiology, University of Zagreb School of Medicine, Šalata 3, 10000 Zagreb, Croatia,
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13
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Mongy NNE, Hilal RF. How far is vitamin D implicated in cutaneous infections. Clin Dermatol 2021; 40:198-205. [PMID: 34893391 DOI: 10.1016/j.clindermatol.2021.10.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Vitamin D is an important cornerstone in the immunologic cascade of many skin infections, systemic infections with cutaneous presentations, and other infectious dermatologic diseases where infections could be a culprit. Vitamin D supplementation is proposed as a protective measure against their occurrence and exacerbation, especially with the emergence of several viral pandemics in recent years. Vitamin D plays a key role in the maintenance of a balanced immunologic profile which could be reflected by a lowered incidence and morbidity of infections. Vitamin D screening and supplementation in patients with deficiencies or insufficiencies should be a part of the dermatologic approach to patients with these diseases.
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Affiliation(s)
- Naglaa Nabil El Mongy
- Professor of Dermatology, Kasr Al Ainy Teaching Hospital, Cairo University, Cairo, Egypt
| | - Rana Fathy Hilal
- Associate Professor of Dermatology, Kasr Al Ainy Teaching Hospital, Cairo University, Cairo, Egypt.
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14
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Kalia V, Studzinski GP, Sarkar S. Role of vitamin D in regulating COVID-19 severity-An immunological perspective. J Leukoc Biol 2021; 110:809-819. [PMID: 33464639 PMCID: PMC8014852 DOI: 10.1002/jlb.4covr1020-698r] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Revised: 11/30/2020] [Accepted: 12/30/2020] [Indexed: 12/23/2022] Open
Abstract
Vitamin D, a key nutrient/prohormone classically associated with skeletal health, is also an important immunomodulator, with pleotropic effects on innate and adaptive immune cells. Outcomes of several chronic, autoimmune, and infectious diseases are linked to vitamin D. Emergent correlations of vitamin D insufficiency with coronavirus-induced disease 2019 (COVID-19) severity, alongside empirical and clinical evidence of immunoregulation by vitamin D in other pulmonary diseases, have prompted proposals of vitamin D supplementation to curb the COVID-19 public health toll. In this review paper, we engage an immunological lens to discuss potential mechanisms by which vitamin D signals might regulate respiratory disease severity in severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infections, vis a vis other pulmonary infections. It is proposed that vitamin D signals temper lung inflammatory cascades during SARS-CoV2 infection, and insufficiency of vitamin D causes increased inflammatory cytokine storm, thus leading to exacerbated respiratory disease. Additionally, analogous to studies of reduced cancer incidence, the dosage of vitamin D compounds administered to patients near the upper limit of safety may serve to maximize immune health benefits and mitigate inflammation and disease severity in SARS-CoV2 infections. We further deliberate on the importance of statistically powered clinical correlative and interventional studies, and the need for in-depth basic research into vitamin D-dependent host determinants of respiratory disease severity.
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Affiliation(s)
- Vandana Kalia
- Department of Pediatrics, Division of Hematology and Oncology, University of Washington School of Medicine, Seattle, Washington, USA
- Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, Washington, USA
| | - George P Studzinski
- Department of Pathology, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA
| | - Surojit Sarkar
- Department of Pediatrics, Division of Hematology and Oncology, University of Washington School of Medicine, Seattle, Washington, USA
- Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, Washington, USA
- Department of Pathology, University of Washington School of Medicine, Seattle, Washington, USA
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15
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Ahluwalia S, Choudhary D, Tyagi P, Kumar V, Vivekanandan P. Vitamin D signaling inhibits HBV activity by directly targeting the HBV core promoter. J Biol Chem 2021; 297:101233. [PMID: 34562448 PMCID: PMC8517215 DOI: 10.1016/j.jbc.2021.101233] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 09/16/2021] [Accepted: 09/21/2021] [Indexed: 12/12/2022] Open
Abstract
Clinical and epidemiological studies support a role for vitamin D in suppressing hepatitis B virus (HBV). This antiviral role of vitamin D is widely attributed to vitamin D receptor (VDR)/retinoid X receptor-mediated regulation of host immunomodulatory genes through vitamin D response elements (VDREs) in their promoters. Here, we investigated the ability of calcitriol (1α,25-dihydroxyvitamin D3, metabolically activated vitamin D) to directly regulate HBV activity through this signaling pathway. We observed that calcitriol selectively inhibited only the HBV core promoter without affecting the HBV-PreS1, HBV-PreS2/S, or HBx promoters. We then identified a VDRE cluster in the HBV core promoter that is highly conserved across most HBV genotypes. Disruption of this VDRE cluster abrogated calcitriol-mediated suppression of the HBV core promoter. Furthermore, we showed that VDR interacts directly with the VDRE cluster in the HBV core promoter independent of retinoid X receptor. This demonstrates that calcitriol inhibits HBV core promoter activity through a noncanonical calcitriol-activated VDR pathway. Finally, we observed that calcitriol suppressed expression of the canonical HBV core promoter transcripts, pregenomic RNA, and precore RNA in multiple HBV cell culture models. In addition, calcitriol inhibited the secretion of hepatitis B "e" antigen and hepatitis B surface antigen (HBV-encoded proteins linked to poor disease prognosis), without affecting virion secretion. Our findings identify VDR as a novel regulator of HBV core promoter activity and also explain at least in part the correlation of vitamin D levels to HBV activity observed in clinical studies. Furthermore, this study has implications on the potential use of vitamin D along with anti-HBV therapies, and lays the groundwork for studies on vitamin D-mediated regulation of viruses through VDREs in virus promoters.
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Affiliation(s)
- Shivaksh Ahluwalia
- Kusuma School of Biological Sciences, Indian Institute of Technology Delhi, New Delhi, India
| | - Divya Choudhary
- Department of Chemical Engineering, Indian Institute of Technology Delhi, New Delhi, India
| | - Purnima Tyagi
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary sciences, New Delhi, India
| | - Vijay Kumar
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary sciences, New Delhi, India
| | - Perumal Vivekanandan
- Kusuma School of Biological Sciences, Indian Institute of Technology Delhi, New Delhi, India.
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16
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Mate A, Reyes-Goya C, Santana-Garrido Á, Sobrevia L, Vázquez CM. Impact of maternal nutrition in viral infections during pregnancy. Biochim Biophys Acta Mol Basis Dis 2021; 1867:166231. [PMID: 34343638 PMCID: PMC8325560 DOI: 10.1016/j.bbadis.2021.166231] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Revised: 07/05/2021] [Accepted: 07/23/2021] [Indexed: 12/11/2022]
Abstract
Other than being a physiological process, pregnancy is a condition characterized by major adaptations of maternal endocrine and metabolic homeostasis that are necessary to accommodate the fetoplacental unit. Unfortunately, all these systemic, cellular, and molecular changes in maternal physiology also make the mother and the fetus more prone to adverse outcomes, including numerous alterations arising from viral infections. Common infections during pregnancy that have long been recognized as congenitally and perinatally transmissible to newborns include toxoplasmosis, rubella, cytomegalovirus, and herpes simplex viruses (originally coined as ToRCH infections). In addition, enterovirus, parvovirus B19, hepatitis virus, varicella-zoster virus, human immunodeficiency virus, Zika and Dengue virus, and, more recently, coronavirus infections including Middle Eastern respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) infections (especially the novel SARS-CoV-2 responsible for the ongoing COVID-19 pandemic), constitute relevant targets for current research on maternal-fetal interactions in viral infections during pregnancy. Appropriate maternal education from preconception to the early postnatal period is crucial to promote healthy pregnancies in general and to prevent and/or reduce the impact of viral infections in particular. Specifically, an adequate lifestyle based on proper nutrition plans and feeding interventions, whenever possible, might be crucial to reduce the risk of virus-related gestational diseases and accompanying complications in later life. Here we aim to provide an overview of the emerging literature addressing the impact of nutrition in the context of potentially harmful viral infections during pregnancy.
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Affiliation(s)
- Alfonso Mate
- Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain; Epidemiología Clínica y Riesgo Cardiovascular, Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, 41013 Sevilla, Spain.
| | - Claudia Reyes-Goya
- Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain
| | - Álvaro Santana-Garrido
- Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain; Epidemiología Clínica y Riesgo Cardiovascular, Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, 41013 Sevilla, Spain
| | - Luis Sobrevia
- Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain; Cellular and Molecular Physiology Laboratory (CMPL), Department of Obstetrics, Division of Obstetrics and Gynaecology, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile; Medical School (Faculty of Medicine), São Paulo State University (UNESP), Brazil; University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine and Biomedical Sciences, University of Queensland, Herston, QLD 4029, Australia; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen (UMCG), 9713GZ Groningen, the Netherlands
| | - Carmen M Vázquez
- Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain; Epidemiología Clínica y Riesgo Cardiovascular, Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, 41013 Sevilla, Spain
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17
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Wu D, Cline-Smith A, Shashkova E, Perla A, Katyal A, Aurora R. T-Cell Mediated Inflammation in Postmenopausal Osteoporosis. Front Immunol 2021; 12:687551. [PMID: 34276675 PMCID: PMC8278518 DOI: 10.3389/fimmu.2021.687551] [Citation(s) in RCA: 101] [Impact Index Per Article: 25.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 06/04/2021] [Indexed: 12/11/2022] Open
Abstract
Osteoporosis is the most prevalent metabolic bone disease that affects half the women in the sixth and seventh decade of life. Osteoporosis is characterized by uncoupled bone resorption that leads to low bone mass, compromised microarchitecture and structural deterioration that increases the likelihood of fracture with minimal trauma, known as fragility fractures. Several factors contribute to osteoporosis in men and women. In women, menopause - the cessation of ovarian function, is one of the leading causes of primary osteoporosis. Over the past three decades there has been growing appreciation that the adaptive immune system plays a fundamental role in the development of postmenopausal osteoporosis, both in humans and in mouse models. In this review, we highlight recent data on the interactions between T cells and the skeletal system in the context of postmenopausal osteoporosis. Finally, we review recent studies on the interventions to ameliorate osteoporosis.
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Affiliation(s)
| | | | | | | | | | - Rajeev Aurora
- Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO, United States
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18
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Zhang J, Ling N, Lei Y, Peng M, Hu P, Chen M. Multifaceted Interaction Between Hepatitis B Virus Infection and Lipid Metabolism in Hepatocytes: A Potential Target of Antiviral Therapy for Chronic Hepatitis B. Front Microbiol 2021; 12:636897. [PMID: 33776969 PMCID: PMC7991784 DOI: 10.3389/fmicb.2021.636897] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 02/18/2021] [Indexed: 12/17/2022] Open
Abstract
Hepatitis B virus (HBV) is considered a “metabolic virus” and affects many hepatic metabolic pathways. However, how HBV affects lipid metabolism in hepatocytes remains uncertain yet. Accumulating clinical studies suggested that compared to non-HBV-infected controls, chronic HBV infection was associated with lower levels of serum total cholesterol and triglycerides and a lower prevalence of hepatic steatosis. In patients with chronic HBV infection, high ALT level, high body mass index, male gender, or old age was found to be positively correlated with hepatic steatosis. Furthermore, mechanisms of how HBV infection affected hepatic lipid metabolism had also been explored in a number of studies based on cell lines and mouse models. These results demonstrated that HBV replication or expression induced extensive and diverse changes in hepatic lipid metabolism, by not only activating expression of some critical lipogenesis and cholesterolgenesis-related proteins but also upregulating fatty acid oxidation and bile acid synthesis. Moreover, increasing studies found some potential targets to inhibit HBV replication or expression by decreasing or enhancing certain lipid metabolism-related proteins or metabolites. Therefore, in this article, we comprehensively reviewed these publications and revealed the connections between clinical observations and experimental findings to better understand the interaction between hepatic lipid metabolism and HBV infection. However, the available data are far from conclusive, and there is still a long way to go before clarifying the complex interaction between HBV infection and hepatic lipid metabolism.
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Affiliation(s)
- Jiaxuan Zhang
- Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Ning Ling
- Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yu Lei
- Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Mingli Peng
- Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Peng Hu
- Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Min Chen
- Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Fiorino S, Zippi M, Gallo C, Sifo D, Sabbatani S, Manfredi R, Rasciti E, Rasciti L, Giampieri E, Corazza I, Leandri P, de Biase D. The rationale for a multi-step therapeutic approach based on antivirals, drugs and nutrients with immunomodulatory activity in patients with coronavirus-SARS2-induced disease of different severities. Br J Nutr 2021; 125:275-293. [PMID: 32703328 PMCID: PMC7431858 DOI: 10.1017/s0007114520002913] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Revised: 06/28/2020] [Accepted: 07/02/2020] [Indexed: 02/07/2023]
Abstract
In December 2019, a novel human-infecting coronavirus, named Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), was recognised to cause a pneumonia epidemic outbreak with different degrees of severity in Wuhan, Hubei Province in China. Since then, this epidemic has spread worldwide; in Europe, Italy has been involved. Effective preventive and therapeutic strategies are absolutely required to block this serious public health concern. Unfortunately, few studies about SARS-CoV-2 concerning its immunopathogenesis and treatment are available. On the basis of the assumption that the SARS-CoV-2 is genetically related to SARS-CoV (about 82 % of genome homology) and that its characteristics, like the modality of transmission or the type of the immune response it may stimulate, are still poorly known, a literature search was performed to identify the reports assessing these elements in patients with SARS-CoV-induced infection. Therefore, we have analysed: (1) the structure of SARS-CoV-2 and SARS-CoV; (2) the clinical signs and symptoms and pathogenic mechanisms observed during the development of acute respiratory syndrome and the cytokine release syndrome; (3) the modification of the cell microRNome and of the immune response in patients with SARS infection; and (4) the possible role of some fat-soluble compounds (such as vitamins A, D and E) in modulating directly or indirectly the replication ability of SARS-CoV-2 and host immune response.
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Affiliation(s)
- Sirio Fiorino
- Medicine Department, Internal Medicine Unit, Budrio Hospital Azienda USL, Budrio, 40054 Bologna, Italy
- Medicine Department, Internal Medicine Unit C, Maggiore Hospital Azienda USL, 40100 Bologna, Italy
| | - Maddalena Zippi
- Gastroenterology and Hepatology Department, Unit of Gastroenterology and Digestive Endoscopy, Sandro Pertini Hospital, 00100 Rome, Italy
| | - Claudio Gallo
- Medicine Department, Internal Medicine Unit, Budrio Hospital Azienda USL, Budrio, 40054 Bologna, Italy
| | - Debora Sifo
- Medicine Department, Internal Medicine Unit, Budrio Hospital Azienda USL, Budrio, 40054 Bologna, Italy
| | - Sergio Sabbatani
- Gastroenterology and Hepatology Department, Infective Disease Unit, Policlinico S. Orsola-Malpighi, University of Bologna, 40100 Bologna, Italy
| | - Roberto Manfredi
- Gastroenterology and Hepatology Department, Infective Disease Unit, Policlinico S. Orsola-Malpighi, University of Bologna, 40100 Bologna, Italy
| | - Edoardo Rasciti
- Unit of Radiodiagnostics, Ospedale degli Infermi, 48018 Faenza, AUSL Romagna, Italy
| | - Leonardo Rasciti
- Medicine Department, Internal Medicine Unit, Budrio Hospital Azienda USL, Budrio, 40054 Bologna, Italy
| | - Enrico Giampieri
- Experimental, Diagnostic and Specialty Medicine Department, University of Bologna, 40100 Bologna, Italy
| | - Ivan Corazza
- Experimental, Diagnostic and Specialty Medicine Department, University of Bologna, 40100 Bologna, Italy
| | - Paolo Leandri
- Medicine Department, Internal Medicine Unit C, Maggiore Hospital Azienda USL, 40100 Bologna, Italy
| | - Dario de Biase
- Department of Pharmacy and Biotechnology, University of Bologna, 40100 Bologna, Italy
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20
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Huang CZ, Zhang J, Zhang L, Yu CH, Mo Y, Mo LY. Serum vitamin D and vitamin-D-binding protein levels in children with chronic hepatitis B. World J Gastroenterol 2021; 27:255-266. [PMID: 33519140 PMCID: PMC7814368 DOI: 10.3748/wjg.v27.i3.255] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 12/29/2020] [Accepted: 01/06/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Vitamin D is an essential fat-soluble secosteroid hydroxylated by the liver to form the intermediate metabolite calcidiol {25-hydroxy vitamin D [25(OH)D]}, which is a reliable indicator to investigate individual vitamin D status. Vitamin-D-binding protein (VDBP) is a multifunctional glycoprotein mainly synthesized in the liver and the major transport protein for vitamin D and its metabolites. Serum vitamin D and VDBP are both associated with hepatitis B. However, few studies have reported the relationship and clinical significance of vitamin D and VDBP with hepatitis B virus (HBV) replication and hepatic fibrosis in children with chronic hepatitis B (CHB).
AIM To explore vitamin D and VDBP serum levels in children with CHB and the association of vitamin D and VDBP with HBV replication and hepatic fibrosis.
METHODS We enrolled 204 children with CHB admitted to Hunan Children’ Hospital in summer and autumn between 2018 and 2019 and 170 healthy controls. CHB patients included: 164 hepatitis B e antigen (HBeAg) positive and 40 HBeAg negative; 193 hepatitis B surface antigen (HBsAg) positive and 11 HBsAg negative; 164 with detectable HBV deoxyribonucleic acid (DNA) and 40 with undetectable HBV DNA; 131 with HBV genotype B and 23 with HBV genotype C; and 27 without hepatic fibrosis and 97 with hepatic fibrosis. Serum levels of 25(OH)D, VDBP, liver function markers, and other clinical parameters were collected to analyze their association with vitamin D and VDBP. Mann-Whitney U test, Kruskal-Wallis H test, or t test was used to analyze serum 25(OH)D and VDBP levels in different groups. Spearman rank correlation test was utilized to analyze the correlation of 25(OH)D and VDBP with other markers. Statistically significant factors determined by univariate analysis were further analyzed by binary multivariate logistic regression analysis. P < 0.05 was considered statistically significant.
RESULTS Children with CHB had lower serum 25(OH)D (56.64 ± 17.89 nmoL/L) and VDBP [122.40 (70.74-262.84 μg/L)] levels than healthy controls had (P < 0.001). Serum 25(OH)D and VDBP levels were significantly different among the different grades of hepatic fibrosis (P < 0.05). VDBP levels in children with HBV genotype C, HBsAg, HBeAg, and detectable HBV DNA were significantly lower than those in children with HBV genotype B, no HBsAg, no HBeAg, and undetectable HBV DNA (P < 0.05). Serum 25(OH)D level was negatively correlated with age and serum total bilirubin level (r = -0.396 and -0.280, respectively, P < 0.001). Serum VDBP level was negatively correlated with HBV DNA (log10 IU/mL) (r = -0.272, P < 0.001). Serum 25(OH)D level was not correlated with VDBP level (P > 0.05). Univariate (P < 0.05) and multivariate logistic regression analysis showed that low level of 25(OH)D (odds ratio = 0.951, 95% confidence interval: 0.918-0.985) and high level of HBV DNA (odds ratio = 1.445, 95% confidence interval: 1.163-1.794) were independently correlated with hepatic fibrosis (P < 0.01).
CONCLUSION Serum levels of 25(OH)D and VDBP are decreased in children with CHB. Serum VDBP level is negatively correlated with HBV replication. Low level of 25(OH)D is independently associated with hepatic fibrosis in children with CHB. There is no significant association between serum levels of 25(OH)D and VDBP.
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Affiliation(s)
- Cai-Zhi Huang
- Department of Laboratory Medicine, Hunan Children’s Hospital, Changsha 410007, Hunan Province, China
| | - Jie Zhang
- Department of Laboratory Medicine, Hunan Children’s Hospital, Changsha 410007, Hunan Province, China
| | - Lin Zhang
- Department of Laboratory Medicine, Hunan Children’s Hospital, Changsha 410007, Hunan Province, China
| | - Cui-Hua Yu
- Department of GCP Certified Sites, The Third Hospital of Changsha City, Changsha 410005, Hunan Province, China
| | - Yi Mo
- Department of Laboratory Medicine, Hunan Children’s Hospital, Changsha 410007, Hunan Province, China
| | - Li-Ya Mo
- Department of Laboratory Medicine, Hunan Children’s Hospital, Changsha 410007, Hunan Province, China
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21
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Brayette A, Essig M, Carrier P, Debette-Gratien M, Labrunie A, Alain S, Maynard M, Ganne-Carrié N, Nguyen-Khac E, Pinet P, De Ledinghen V, Renou C, Mathurin P, Vanlemmens C, Di Martino V, Gervais A, Foucher J, Isabelle FH, Vergniol J, Hourmand-Ollivier I, Cohen D, Duval X, Poynard T, Bardou M, Abergel A, Dao MT, Thévenot T, Hiriart JB, Canva V, Lassailly G, Aurières C, Boyer N, Thabut D, Bernard PH, Schnee M, Larrey D, Hanslik B, Hommel S, Jacques J, Loustaud-Ratti V. Subclinical proximal tubulopathy in hepatitis B: The roles of nucleot(s)ide analogue treatment and the hepatitis B virus. World J Hepatol 2020; 12:1326-1340. [PMID: 33442458 PMCID: PMC7772739 DOI: 10.4254/wjh.v12.i12.1326] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 10/07/2020] [Accepted: 10/28/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The recommended monitoring tools for evaluating nucleot(s)ide analogue renal toxicity, such as estimated glomerular filtration rate (eGFR) and phosphatemia, are late markers of proximal tubulopathy. Multiple early markers are available, but no consensus exists on their use. AIM To determine the 24 mo prevalence of subclinical proximal tubulopathy (SPT), as defined with early biomarkers, in treated vs untreated hepatitis B virus (HBV)-monoinfected patients. METHODS A prospective, non-randomized, multicenter study of HBV-monoinfected patients with a low number of renal comorbidities was conducted. The patients were separated into three groups: Naïve, starting entecavir (ETV) treatment, or starting tenofovir disoproxil (TDF) treatment. Data on the early markers of SPT, the eGFR and phosphatemia, were collected quarterly. SPT was defined as a maximal tubular reabsorption of phosphate/eGFR below 0.8 mmoL/L and/or uric acid fractional excretion above 10%. The prevalence and cumulative incidence of SPT at month 24 (M24) were calculated. Quantitative data were analyzed using analyses of variance or Kruskal-Wallis tests, whereas chi-squared or Fisher's exact tests were used to analyze qualitative data. Multivariate analyses were used to adjust for any potential confounding factors. RESULTS Of the 196 patients analyzed, 138 (84 naïve, 28 starting ETV, and 26 starting TDF) had no SPT at inclusion. At M24, the prevalence of SPT was not statistically different between naïve and either treated group (21.1% vs 30.7%, P < 0.42 and 50.0% vs 30.7%, P = 0.32 for ETV and TDF, respectively); no patient had an eGFR lower than 50 mL/min/1.73 m² or phosphatemia less than 0.48 mmoL/L. In the multivariate analysis, no explanatory variables were identified after adjustment. The cumulative incidence of SPT over 24 mo (25.5%, 13.3%, and 52.9% in the naïve, ETV, and TDF groups, respectively) tended to be higher in the TDF group vs the naïve group (hazard ratio: 2.283, P = 0.05). SPT-free survival at M24 was 57.6%, 68.8%, and 23.5% for the naïve, ETV, and TDF groups, respectively. The median survival time without SPT, evaluated only in the TDF group, was 5.9 mo. CONCLUSION The prevalence and incidence of SPT was higher in TDF-treated patients compared to naïve patients. SPT in the naïve population suggests that HBV can induce renal tubular toxicity.
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Affiliation(s)
- Anaïs Brayette
- U1248 INSERM, Department of Hepatology and Gastroenterology, Univ. Limoges, CHU Limoges, Limoges F-87000, France
| | - Marie Essig
- U1248 INSERM, Department of Nephrology and Transplantation, CHU Limoges, Limoges F-87000, France
| | - Paul Carrier
- U1248 INSERM, Department of Hepatology and Gastroenterology, Univ. Limoges, CHU Limoges, Limoges F-87000, France
| | - Marilyne Debette-Gratien
- U1248 INSERM, Department of Hepatology and Gastroenterology, Univ. Limoges, CHU Limoges, Limoges F-87000, France
| | - Anaïs Labrunie
- Department of Center of Epidemiology, Biostatistics and Research Methodology, CHU Limoges, Limoges F-87000, France
| | - Sophie Alain
- U1092 INSERM, Department of Virology, CHU Limoges, Limoges F-87000, France
| | - Marianne Maynard
- Department of Hepatology, Croix-Rousse University Hospital of Lyon, Lyon 69004, France
| | - Nathalie Ganne-Carrié
- Department of Hepatology, Jean Verdier University Hospital of Bondy, Bondy 93140, France
| | - Eric Nguyen-Khac
- Department of Hepato-Gastroenterology, Amiens University Hospital, Amiens 80054, France
| | - Pauline Pinet
- Department of Infectious Diseases, CHU Limoges, Limoges F-87000, France
| | - Victor De Ledinghen
- Department of Hepatology, Haut Leveque Hospital, Bordeaux University Hospital, Pessac 33604, France
| | - Christophe Renou
- Department of Gastroenterology, Hyeres Hospital, Hyeres 83407, France
| | - Philippe Mathurin
- Department of Hepato-Gastroenterology, Claude Huriez University Hospital, Lille 59037, France
| | - Claire Vanlemmens
- Department of Hepatology, Jean Minjoz University Hospital, Besançon 25030, France
| | - Vincent Di Martino
- Department of Hepatology, Jean Minjoz University Hospital, Besançon 25030, France
| | - Anne Gervais
- Department of Infectious Diseases, Bichat University Hospital, Paris 75018, France
| | - Juliette Foucher
- Department of Hepatology, Haut Leveque Hospital, Bordeaux University Hospital, Pessac 33604, France
| | | | - Julien Vergniol
- Department of Hepatology, Haut Leveque Hospital, Bordeaux University Hospital, Pessac 33604, France
| | | | - Daniel Cohen
- Department of General Medecine, University Hospital of Caen, Caen 14000, France
| | - Xavier Duval
- Department of Infectious Diseases, Bichat University Hospital, Paris 75018, France
| | - Thierry Poynard
- Department of Hepatology, La Pitié-Salpêtrière University Hospital, Paris 75651, France
| | - Marc Bardou
- Department of Hepatology and Gastroenterology, Dijon University Hospital, Dijon 21079, France
| | - Armand Abergel
- Department of Hepatology and Gastroenterology, Estaing University Hospital, Clermont Ferrand 63003, France
| | - Manh-Thong Dao
- Department of Hepato-Gastroenterology and Nutrition, University Hospital of Caen, Caen 14033, France
| | - Thierry Thévenot
- Department of Hepatology, Jean Minjoz University Hospital, Besançon 25030, France
| | - Jean-Baptiste Hiriart
- Department of Hepatology, Haut Leveque Hospital, Bordeaux University Hospital, Pessac 33604, France
| | - Valérie Canva
- Department of Hepato-Gastroenterology, Claude Huriez University Hospital, Lille 59037, France
| | - Guillaume Lassailly
- Department of Hepato-Gastroenterology, Claude Huriez University Hospital, Lille 59037, France
| | - Christine Aurières
- Department of Hepatology, Beaujon University Hospital, Clichy 92110, France
| | - Nathalie Boyer
- Department of Hepatology, Beaujon University Hospital, Clichy 92110, France
| | - Dominique Thabut
- Department of Hepatology, La Pitié-Salpêtrière University Hospital, Paris 75651, France
| | - Pierre-Henri Bernard
- Department of Hepatology, Saint-André University Hospital, Bordeaux 33000, France
| | - Matthieu Schnee
- Department of Hepatology and Gastroenterology, La Roche-Sur-Yon Hospital Center, La Roche-Sur-Yon 85000, France
| | - Dominique Larrey
- Department of Hepatology and Gastroenterology, University Hospital of Montpellier, Montpellier 34295, France
| | - Bertrand Hanslik
- Department of Addictology, Hospital of Montpellier, Montpellier 34295, France
| | - Séverine Hommel
- Department of Hepatology and Gastroenterology, Hospital Center of Aix en Provence, Aix-en-Provence 13100, France
| | - Jérémie Jacques
- U1248 INSERM, Department of Hepatology and Gastroenterology, Univ. Limoges, CHU Limoges, Limoges F-87000, France
| | - Véronique Loustaud-Ratti
- U1248 INSERM, Department of Hepatology and Gastroenterology, Univ. Limoges, CHU Limoges, Limoges F-87000, France.
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22
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Mahran SA, Mohamed AAA, Nigm DA, Rahma MZAA, Abd-Elsalam S, Hamoud H, Hamdy M, Risha MI, Hamdy A, Abdelkareem MM, Ghanem S, Hanafy M, Moshrif A, Fehr A, ElNouby FH, Osman A, Hassanien MM. Subclinical hepatitis C virus infection in Egyptian patients with rheumatic diseases: a multi-center study. EGYPTIAN RHEUMATOLOGY AND REHABILITATION 2020; 47:1. [DOI: 10.1186/s43166-020-00014-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Accepted: 05/18/2020] [Indexed: 02/08/2023] Open
Abstract
Abstract
Background
Hepatitis C virus (HCV) infection is highly prevalent in Egypt. It was found to be 7.0% in a study done in 2015. There are some studies on the prevalence of HCV in rheumatoid arthritis, but to our knowledge, no previous study was done to detect it in other rheumatologic diseases. This study aims at detecting the prevalence of subclinical HCV infection in Egyptian patients with different rheumatic diseases. In the current study, eight hundred and three patients with different rheumatic diseases collected from five—geographically different—Egyptian rheumatology departments were studied. Patients with known current or previous HCV infection were excluded from the study. Screening for the positive anti-HCV antibodies was done for all patients. Screening for the presence of HCV ribonucleic acid (RNA) was done in patients with positive serology by reverse transcriptase-polymerase chain reaction.
Results
In the studied population, 675 (84.1%) patients were women. The mean age [± SD] was 44.2 [± 12.9] years. Hepatitis C antibody positivity was found in 73 (9.1%) of the patients, while 67 (8.3%) were having positive HCV-RNA quantitative PCR tests. The highest prevalence of seropositive HCV was found in drug-induced vasculitis (DIV) and cryo-vasculitis (100%), while in RA, HCV antibodies and PCR were found to be positive in 9.1% and 8.3% of patients, respectively.
Conclusions
Detection of the presence of HCV infection in 9.1 % of the studied middle-aged Egyptian patients with rheumatologic conditions points to the importance of screening for HCV in such population for early detection and intervention especially for those patients that are planned to start biologic therapy.
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23
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Wang CC, Tzeng IS, Su WC, Li CH, Lin HH, Yang CC, Kao JH. The association of vitamin D with hepatitis B virus replication: Bystander rather than offender. J Formos Med Assoc 2020; 119:1634-1641. [PMID: 31932201 DOI: 10.1016/j.jfma.2019.12.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Revised: 11/10/2019] [Accepted: 12/16/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND/PURPOSE Low vitamin D is frequent in hepatitis B virus (HBV)-infected patients and several studies show an inverse association of serum vitamin D level with HBV viral load. However, the causal relationship remains unclear. METHODS HBV carriers receiving regular 6-month surveillance without current antiviral treatment or cirrhosis were invited to participate into this trial. The markers of HBV replication included serum HBV DNA and quantitative HBsAg (qHBsAg) levels. Those with undetectable HBV DNA or sufficient vitamin D levels, cancer or electrolyte imbalance were excluded. The eligible subjects were randomized to receive either vitamin D supplement 2000 IU per day for 2 months (vitamin D group) or none (control group). RESULTS A total of 196 HBV carriers (93 males and 103 females; mean age 51.9 ± 10.0 years) were screened. Of them, 28 patients had undetectable serum HBV DNA levels, which is defined as spontaneous viral clearance. The vitamin D levels were not different between patients with detectable HBV DNA and those without (p = 0.18). After exclusion, 149 patients were randomized to two groups: 75 in vitamin D group and 74 in control group. After 2 months vitamin D supplement, the serum vitamin D levels were significantly higher in the vitamin D group than the control group (p < 0.001). However, the serum qHBsAg and HBV DNA levels were comparable between these two groups. CONCLUSION There is no causal relationship between vitamin D and HBV replication. The role of liver reserve on serum vitamin D levels in patients with chronic HBV infection needs further investigation.
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Affiliation(s)
- Chia-Chi Wang
- Department of Gastroenterology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, Hualien, Taiwan.
| | - I-Shiang Tzeng
- Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan
| | - Wei-Chih Su
- Department of Gastroenterology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Chung-Hsien Li
- Department of Gastroenterology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Hans Hsienhong Lin
- Department of Gastroenterology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Chun-Chun Yang
- Department of Laboratory Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taiwan
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine and Hepatitis Research Center, National Taiwan University College of Medicine and Hospital, Taiwan
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24
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Yin J, Yin LY, Freedman ND, Li TY, Dawsey SM, Cui JF, Taylor PR, Liu B, Fan JH, Chen W, Abnet CC, Qiao YL. Independent and Joint Associations between Serum Calcium, 25-Hydroxy Vitamin D, and the Risk of Primary Liver Cancer: A Prospective Nested Case-Control Study. Cancer Epidemiol Biomarkers Prev 2020; 29:2057-2064. [PMID: 32856608 PMCID: PMC8594771 DOI: 10.1158/1055-9965.epi-20-0417] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Revised: 05/27/2020] [Accepted: 07/31/2020] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Accumulating evidence has shown that serum calcium and vitamin D may be associated with or influence various cancer risks. However, no prospective studies have evaluated the independent and joint associations between prediagnostic levels of serum calcium and vitamin D and future risk of incident primary liver cancer. METHODS We used a nested case-control design to evaluate subjects over 22 years of follow-up. Serum calcium, 25-hydroxy vitamin D [25(OH)D], and three markers of hepatitis B virus and hepatitis C virus were measured in baseline serum from 226 incident primary liver cancer cases and 1,061 matched controls. We calculated ORs and 95% confidence intervals (CI) using logistic regression to estimate the associations between calcium, 25(OH)D, and primary liver cancer risk. RESULTS Multivariable adjusted models showed that subjects with both low (ORLow/Medium = 1.48, 95% CI = 1.01-2.17) or high (ORHigh/Medium = 1.92, 95% CI = 1.34-2.76) calcium had an increased primary liver cancer risk, while those with high 25(OH)D had a decreased risk of primary liver cancer (ORHigh/Medium = 0.54, 95% CI = 0.35-0.82). In joint analyses, when compared with subjects with medium calcium and 25(OH)D, subjects with high calcium and medium 25(OH)D had elevated odds of developing primary liver cancer (OR = 1.89, 95% CI = 1.17-3.05); those with medium calcium and high 25(OH)D had reduced odds of developing primary liver cancer (OR = 0.34, 95% CI = 0.17-0.67); and subjects in other classifications of calcium and serum 25(OH)D levels had no change in the odds of developing primary liver cancer (all P > 0.05). CONCLUSIONS In a nutrient-deficient population, we found that serum calcium and serum 25(OH)D could potentially be modifiable risk or protective factors. IMPACT Our findings provide potential targets for primary liver cancer prevention and control.
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Affiliation(s)
- Jian Yin
- Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Liang-Yu Yin
- Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
- Department of Clinical Nutrition, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Neal D Freedman
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland
| | - Ting-Yuan Li
- Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Sanford M Dawsey
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland
| | - Jian-Feng Cui
- Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Philip R Taylor
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland
| | - Bin Liu
- Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jin-Hu Fan
- Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wen Chen
- Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| | - Christian C Abnet
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland
| | - You-Lin Qiao
- Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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25
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Fiorino S, Gallo C, Zippi M, Sabbatani S, Manfredi R, Moretti R, Fogacci E, Maggioli C, Travasoni Loffredo F, Giampieri E, Corazza I, Dickmans C, Denitto C, Cammarosano M, Battilana M, Orlandi PE, Del Forno F, Miceli F, Visani M, Acquaviva G, De Leo A, Leandri P, Hong W, Brand T, Tallini G, Jovine E, Jovine R, de Biase D. Cytokine storm in aged people with CoV-2: possible role of vitamins as therapy or preventive strategy. Aging Clin Exp Res 2020; 32:2115-2131. [PMID: 32865757 PMCID: PMC7456763 DOI: 10.1007/s40520-020-01669-y] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Accepted: 07/21/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND In December 2019, a novel human-infecting coronavirus, SARS-CoV-2, had emerged. The WHO has classified the epidemic as a "public health emergency of international concern". A dramatic situation has unfolded with thousands of deaths, occurring mainly in the aged and very ill people. Epidemiological studies suggest that immune system function is impaired in elderly individuals and these subjects often present a deficiency in fat-soluble and hydrosoluble vitamins. METHODS We searched for reviews describing the characteristics of autoimmune diseases and the available therapeutic protocols for their treatment. We set them as a paradigm with the purpose to uncover common pathogenetic mechanisms between these pathological conditions and SARS-CoV-2 infection. Furthermore, we searched for studies describing the possible efficacy of vitamins A, D, E, and C in improving the immune system function. RESULTS SARS-CoV-2 infection induces strong immune system dysfunction characterized by the development of an intense proinflammatory response in the host, and the development of a life-threatening condition defined as cytokine release syndrome (CRS). This leads to acute respiratory syndrome (ARDS), mainly in aged people. High mortality and lethality rates have been observed in elderly subjects with CoV-2-related infection. CONCLUSIONS Vitamins may shift the proinflammatory Th17-mediated immune response arising in autoimmune diseases towards a T-cell regulatory phenotype. This review discusses the possible activity of vitamins A, D, E, and C in restoring normal antiviral immune system function and the potential therapeutic role of these micronutrients as part of a therapeutic strategy against SARS-CoV-2 infection.
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Affiliation(s)
- Sirio Fiorino
- UO of Internal Medicine Unit, Hospital of Budrio, Via Benni 44, 40065, Budrio, Bologna, Italy.
- Internal Medicine Unit, Maggiore Hospital of Bologna, Bologna, Italy.
| | - Claudio Gallo
- Physician Specialist in Infectious Diseases, AUSL Bologna, Bologna, Italy
| | - Maddalena Zippi
- Unit of Gastroenterology and Digestive Endoscopy, Sandro Petrini Hospital, Rome, Italy
| | | | | | - Renzo Moretti
- UO of Internal Medicine Unit, Hospital of Budrio, Via Benni 44, 40065, Budrio, Bologna, Italy
| | - Elisa Fogacci
- UO of Internal Medicine Unit, Hospital of Budrio, Via Benni 44, 40065, Budrio, Bologna, Italy
| | - Caterina Maggioli
- UO of Internal Medicine Unit, Hospital of Budrio, Via Benni 44, 40065, Budrio, Bologna, Italy
| | | | - Enrico Giampieri
- Experimental, Diagnostic and Specialty Medicine Department, University of Bologna, Bologna, Italy
| | - Ivan Corazza
- Experimental, Diagnostic and Specialty Medicine Department, University of Bologna, Bologna, Italy
| | - Christoph Dickmans
- UO of Internal Medicine Unit, Hospital of Budrio, Via Benni 44, 40065, Budrio, Bologna, Italy
| | - Claudio Denitto
- UO of Internal Medicine Unit, Hospital of Budrio, Via Benni 44, 40065, Budrio, Bologna, Italy
| | - Michele Cammarosano
- UO of Internal Medicine Unit, Hospital of Budrio, Via Benni 44, 40065, Budrio, Bologna, Italy
| | - Michele Battilana
- UO of Internal Medicine Unit, Hospital of Budrio, Via Benni 44, 40065, Budrio, Bologna, Italy
| | | | | | - Francesco Miceli
- UO Farmacia Centralizzata OM, Farmacia Ospedale Di Budrio, Budrio, Bologna, Italy
| | - Michela Visani
- Department of Pharmacy and Biotechnology (FABIT), University of Bologna, Bologna, Italy
- Department of Medicine (Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale), Molecular Diagnostic Unit, University of Bologna, Azienda USL di Bologna, Bologna, Italy
| | - Giorgia Acquaviva
- Department of Medicine (Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale), Molecular Diagnostic Unit, University of Bologna, Azienda USL di Bologna, Bologna, Italy
| | - Antonio De Leo
- Department of Medicine (Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale), Molecular Diagnostic Unit, University of Bologna, Azienda USL di Bologna, Bologna, Italy
| | - Paolo Leandri
- Internal Medicine Unit, Maggiore Hospital of Bologna, Bologna, Italy
| | - Wandong Hong
- Department of Gastroenterology and Hepatology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, The People's Republic of China
| | - Thomas Brand
- Regenerative Medicine Center Utrecht, University of Utrecht, Utrecht, Netherlands
| | - Giovanni Tallini
- Department of Medicine (Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale), Molecular Diagnostic Unit, University of Bologna, Azienda USL di Bologna, Bologna, Italy
| | - Elio Jovine
- Surgery Unit, Maggiore Hospital, Bologna, Italy
| | - Roberto Jovine
- Physical Medicine and Rehabilitation Unit, Maggiore Hospital, Bologna, Italy
| | - Dario de Biase
- Department of Pharmacy and Biotechnology (FABIT), University of Bologna, Bologna, Italy
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Waldenström J, Nyström K, Nilsson S, Norkrans G, Ydreborg M, Langeland N, Mørch K, Westin J, Lagging M. The relation of 25-hydroxy vitamin D concentrations to liver histopathology, seasonality and baseline characteristics in chronic hepatitis C virus genotype 2 or 3 infection. PLoS One 2020; 15:e0237840. [PMID: 32822420 PMCID: PMC7442235 DOI: 10.1371/journal.pone.0237840] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Accepted: 08/02/2020] [Indexed: 02/06/2023] Open
Abstract
Background and objectives The hydroxylation to 25-hydroxy vitamin D (25(OH)D) occurs in the liver and the impact of liver disease on vitamin D is unclear. This study evaluated the relationship between vitamin D concentrations and hepatic histopathology, seasonality and patient characteristics in well-characterized patients having undergone a liver biopsy. Method 25(OH)D was measured post-hoc in pre-treatment serum from 331 North European patients with chronic HCV genotype 2 or 3 infection (NORDynamIC study). Liver biopsies were scored for fibrosis and inflammation according to the Ishak protocol, and graded for steatosis. Non-invasive markers of hepatic fibrosis as well as baseline viral and host characteristics, including genetic polymorphisms rs2228570, rs7975232, and rs10877012 were also evaluated. Results Mean 25(OH)D concentration was 59 ±23 nmol/L, with 41% having values <50 nmol/L and 6% were <30 nmol/L. 25(OH)D correlated with fibrosis (r = -0.10, p ≤0.05) in univariate but not in multivariate analyses. No association was observed between 25(OH)D and hepatic inflammation, but with steatosis in HCV genotype 2 infected patients. None of the genetic polymorphisms impacted on 25(OH)D levels or fibrosis. 25(OH)D levels were significantly inversely correlated to BMI (r = -0.19, p = 0.001), and was also associated with season and non-Caucasian ethnicity. Conclusion Fibrosis was not independently associated with 25(OH)D concentration and no association was seen with hepatic inflammation, but HCV genotype 2 infected patients with moderate-to-severe steatosis had lower 25(OH)D levels compared to those without steatosis. A high percentage had potential risk of 25(OH)D deficiency, and BMI, seasonality and ethnicity were independently associated with 25(OH)D as previously reported.
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Affiliation(s)
- Jesper Waldenström
- Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Region Västra Götaland, Sahlgrenska University Hospital, Department of Clinical Microbiology, Gothenburg, Sweden
- * E-mail:
| | - Kristina Nyström
- Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Region Västra Götaland, Sahlgrenska University Hospital, Department of Clinical Microbiology, Gothenburg, Sweden
| | - Staffan Nilsson
- Department of Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden
| | - Gunnar Norkrans
- Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Magdalena Ydreborg
- Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Region Västra Götaland, Sahlgrenska University Hospital, Department of Clinical Microbiology, Gothenburg, Sweden
| | - Nina Langeland
- Department of Medicine, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Kristine Mørch
- Department of Medicine, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Johan Westin
- Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Region Västra Götaland, Sahlgrenska University Hospital, Department of Clinical Microbiology, Gothenburg, Sweden
| | - Martin Lagging
- Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Region Västra Götaland, Sahlgrenska University Hospital, Department of Clinical Microbiology, Gothenburg, Sweden
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The Study of Correlation Between Serum Vitamin D 3 Concentrations and HBV DNA Levels and Immune Response in Chronic Hepatitis Patients. Nutrients 2020; 12:nu12041114. [PMID: 32316365 PMCID: PMC7230547 DOI: 10.3390/nu12041114] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 04/14/2020] [Accepted: 04/14/2020] [Indexed: 02/07/2023] Open
Abstract
Chronic hepatitis B (CHB) is a common chronic disease. Previous studies have shown a link between 25-hydroxyvitamin D3 (vitamin D3) concentration and liver disease. Hepatitis B virus (HBV) infection has been attributed to the inappropriate functioning of cell-mediated immunity. However, the effects of vitamin D3, immune cell, and HBeAg status on HBV viral load in CHB patients are still unclear. We investigated the relationship between the serum concentration of vitamin D3, percentage of immune cells in peripheral blood, and the HBV viral load of CHB patients. Sixty CHB patients were recruited, and their blood samples were collected and analyzed. Vitamin D level was measured using a chemiluminescence assay. A level of 30 ng/mL or above was defined as a vitamin D3 sufficiency. We assigned vitamin D3 status as either normal (≥30 ng/mL), insufficient (20-30 ng/mL), or deficient (<20 ng/mL). T-lymphocyte and B-lymphocyte surface markers in peripheral blood were detected using flow cytometry. The factors associated with HBV viral load were analyzed using univariate and multivariate-adjusted models. The mean serum vitamin D3 concentration in the subjects was 20.9±5.6 ng/mL. Up to 88.3% of the patients were either deficient in or had insufficient vitamin D3. The gender, BMI, hepatitis B surface antigen levels, and ALT levels were significantly related to serum vitamin D3 levels. Serum vitamin D3 concentration, HBe status, HBs levels, ALT, and AST levels showed a statistically significant correlation with the HBV DNA levels. Serum vitamin D3 concentrations and hepatitis B surface antigen levels were strongly correlated with HBV DNA levels. Vitamin D3 levels were significantly associated with CD19 numbers (β:-6.2, 95% CI: -10.5). In multivariate analysis, vitamin D3 levels in the deficient and insufficient groups, and the CD8, HBeAg, and WBC counts were significantly associated with HBV DNA levels. In the immune tolerance phase of HBeAg-negative chronic HBV infection, vitamin D3 may be a modulator of immune function via CD8, CD19, and HBV DNA.
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Hoan NX, Khuyen N, Giang DP, Binh MT, Toan NL, Anh DT, Trung NT, Bang MH, Meyer CG, Velavan TP, Song LH. Vitamin D receptor ApaI polymorphism associated with progression of liver disease in Vietnamese patients chronically infected with hepatitis B virus. BMC MEDICAL GENETICS 2019; 20:201. [PMID: 31864292 PMCID: PMC6925483 DOI: 10.1186/s12881-019-0903-y] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Accepted: 10/03/2019] [Indexed: 02/06/2023]
Abstract
Background Vitamin D derivatives and their receptor (VDR) are potent modulators of immune responses in various diseases including malignancies as well as in metabolic and infectious disorders. The impact of vitamin D receptor polymorphisms on clinical outcomes of hepatitis B virus (HBV) infection is not well understood. This study aims to investigate the potential role of VDR polymorphisms (TaqI, FokI, ApaI, and BsmI) in Vietnamese HBV infected patients and to correlate these polymorphisms with the progression of HBV-related liver disease. Methods Four hundred forty-three HBV infected patients of the three clinically well-defined subgroups chronic hepatitis B (CHB, n = 183), liver cirrhosis (LC, n = 89) and hepatocellular carcinoma (HCC, n = 171) and 238 healthy individuals (HC) were enrolled. VDR polymorphisms were genotyped by DNA sequencing and in-house validated ARMS assays. Logistic regression models were applied in order to determine the association of VDR polymorphisms with manifest HBV infection as well as with progression of related liver diseases mulin different genetic models. Results The VDR ApaI CA genotype was less frequent in HCC than in CHB patients in different genetic models (codominant model, OR = 0.5, 95%CI = 0.3–0.84, P = 0.004; dominant model, OR = 0.46, 95%CI = 0.27–0.76, P = 0.0023). In the recessive model, the genotype ApaI AA was found more frequently among HCC compared to CHB patients (OR = 2.56, 95%CI = 1.01–6.48, P = 0.04). Similarly, the ApaI CA genotype was less frequent in HCC than in non-HCC group codominant model, OR = 0.6, 95%CI = 0.4–0.98, dominant model, P = 0.04 and OR = 0.6, 95%CI = 0.38–0.90, P = 0.017). The ApaI genotypes CA and AA was significantly associated with higher levels of liver enzymes, bilirubin, and HBV DNA (P < 0.05). No association between TaqI, FokI and BsmI polymorphisms and any clinical outcome as well as liver disease progression was found. Conclusions Among the four investigated VDR polymorphisms, ApaI is associated with clinical outcome and liver disease progression in Vietnamese HBV infected patients.
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Affiliation(s)
- Nghiem Xuan Hoan
- Institute of Clinical Infectious Diseases, 108 Institute of Clinical Medical and Pharmaceutical Sciences, 108 Military Central Hospital, Tran Hung Dao Street N1, Hai Ba Trung District, Hanoi, Vietnam. .,Faculty of Tropical and Infectious Diseases, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam. .,Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany. .,Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam.
| | - Nguyen Khuyen
- Department of Infectious Diseases, Duc Giang Hospital, Hanoi, Vietnam
| | - Dao Phuong Giang
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.,Department of Molecular Biology, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam
| | - Mai Thanh Binh
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.,Department of Gastroenterology, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam
| | - Nguyen Linh Toan
- Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam.,Department of Pathophysiology, Vietnam Military Medical University, Hanoi, Vietnam
| | - Do Tuan Anh
- Department of Infectious Diseases, 103 Military Hospital, Hanoi, Vietnam
| | - Ngo Tat Trung
- Faculty of Tropical and Infectious Diseases, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam.,Department of Molecular Biology, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam
| | - Mai Hong Bang
- Faculty of Tropical and Infectious Diseases, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam.,Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam.,Department of Gastroenterology, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam
| | - Christian G Meyer
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.,Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam.,Duy Tan University, Da Nang, Vietnam
| | - Thirumalaisamy P Velavan
- Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.,Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam.,Duy Tan University, Da Nang, Vietnam
| | - Le Huu Song
- Institute of Clinical Infectious Diseases, 108 Institute of Clinical Medical and Pharmaceutical Sciences, 108 Military Central Hospital, Tran Hung Dao Street N1, Hai Ba Trung District, Hanoi, Vietnam. .,Faculty of Tropical and Infectious Diseases, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam. .,Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam.
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Martínez-Moreno J, Hernandez JC, Urcuqui-Inchima S. Effect of high doses of vitamin D supplementation on dengue virus replication, Toll-like receptor expression, and cytokine profiles on dendritic cells. Mol Cell Biochem 2019; 464:169-180. [PMID: 31758375 DOI: 10.1007/s11010-019-03658-w] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Accepted: 11/16/2019] [Indexed: 01/18/2023]
Abstract
Dengue, caused by dengue virus (DENV) infection, is a public health problem worldwide. Although DENV pathogenesis has not yet been fully elucidated, the inflammatory response is a hallmark feature in severe DENV infection. Although vitamin D (vitD) can promote the innate immune response against virus infection, no studies have evaluated the effects of vitD on DENV infection, dendritic cells (DCs), and inflammatory response regulation. This study aimed to assess the impact of oral vitD supplementation on DENV-2 infection, Toll-like receptor (TLR) expression, and both pro- and anti-inflammatory cytokine production in monocyte-derived DCs (MDDCs). To accomplish this, 20 healthy donors were randomly divided into two groups and received either 1000 or 4000 international units (IU)/day of vitD for 10 days. During pre- and post-vitD supplementation, peripheral blood samples were taken to obtain MDDCs, which were challenged with DENV-2. We found that MDDCs from donors who received 4000 IU/day of vitD were less susceptible to DENV-2 infection than MDDCs from donors who received 1000 IU/day of vitD. Moreover, these cells showed decreased mRNA expression of TLR3, 7, and 9; downregulation of IL-12/IL-8 production; and increased IL-10 secretion in response to DENV-2 infection. In conclusion, the administration of 4000 IU/day of vitD decreased DENV-2 infection. Our findings support a possible role of vitD in improving the innate immune response against DENV. However, further studies are necessary to determine the role of vitD on DENV replication and its innate immune response modulation in MDDCs.
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Affiliation(s)
- Jahnnyer Martínez-Moreno
- Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No. 52-21, 050010, Medellín, Colombia
| | - Juan C Hernandez
- Infettare, Facultad de Medicina, Universidad Cooperativa de Colombia, 050012, Medellín, Colombia
| | - Silvio Urcuqui-Inchima
- Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No. 52-21, 050010, Medellín, Colombia.
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Lin YT, Wang LK, Hung KC, Wu ZF, Chang CY, Chen JY. Patient characteristics and analgesic efficacy of antiviral therapy in postherpetic neuralgia. Med Hypotheses 2019; 131:109323. [PMID: 31443749 DOI: 10.1016/j.mehy.2019.109323] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2019] [Accepted: 07/20/2019] [Indexed: 01/16/2023]
Abstract
Postherpetic neuralgia (PHN) is the most common complication of shingles caused by reactivation of varicella zoster virus (VZV). Management of PHN is often suboptimal while using current conventional treatments. Antiviral therapy was used to reduce PHN-associated pain in two small trials which showed conflicting results. We hypothesize the analgesic efficacy of antiviral therapy on PHN is affected by patient characteristics including pathophysiology of the participants and serum vitamin D levels. Pathophysiology of PHN includes neuronal excitability and chronic VZV ganglionitis (persistent active VZV infection in ganglions). VZV-DNA positivity or a positive IgG coupled with a positive IgM indicates recent or current VZV infection. Positive VZV-DNA or IgG/IgM tests are used to confirm whether the patients experience chronic VZV ganglionitis. Antiviral therapy decreases pain in PHN patients with chronic VZV ganglionitis; whereas, antiviral therapy shows no effects in PHN patients with negative VZV-DNA or IgM. Vitamin D is a natural antiviral mediator. Studies show a high prevalence of vitamin D deficiency in hepatitis B/C virus-infected patients. Serum vitamin D levels and vitamin D supplementation are factors which affect the antiviral efficacy on hepatitis B/C virus infection. Serum 25-OHD levels of hospitalized patients with shingles were significantly lower compared to healthy controls. Accordingly, PHN patient may have a high prevalence of vitamin D deficiency which negatively affects the antiviral efficacy. Vitamin D supplementation may improve the antiviral efficacy on PHN. Future trials regarding antiviral therapy on PHN should consider patient characteristics and should be conducted among different subgroups of PHN patients.
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Affiliation(s)
- Yao-Tsung Lin
- Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan; Department of Food Science and Technology, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
| | - Li-Kai Wang
- Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan
| | - Kuo-Chuan Hung
- Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan
| | - Zhi-Fu Wu
- Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan
| | - Chia-Yu Chang
- Department of Neurology, Chi Mei Medical Center, Tainan, Taiwan; The Center for General Education, Southern Taiwan University of Science and Technology, Tainan, Taiwan
| | - Jen-Yin Chen
- Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan; Department of the Senior Citizen Service Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
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Arruche M, Varas J, Rincón A, Ramos R, Moreno D, Cabré C. ¿Influye la vitamina D en los anticuerpos de superficie de la hepatitis B en pacientes no vacunados en hemodiálisis? Nefrologia 2019; 39:442-443. [DOI: 10.1016/j.nefro.2018.11.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Accepted: 11/05/2018] [Indexed: 11/25/2022] Open
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Ayadi A, Nafari AH, Sakhaee F, Rajabi K, Ghaderi Y, Rahimi Jamnani F, Vaziri F, Siadat SD, Fateh A. Host genetic factors and clinical parameters influencing the occult hepatitis C virus infection in patients on chronic hemodialysis: Is it still a controversial infection? Hepatol Res 2019; 49:605-616. [PMID: 30821879 DOI: 10.1111/hepr.13325] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Revised: 02/04/2019] [Accepted: 02/21/2019] [Indexed: 12/11/2022]
Abstract
AIM The presence of occult hepatitis C virus (HCV) infection (OCI) is still controversial, however, this infection cannot be ignored. Therefore, the current study aimed at assessing the OCI frequency in patients on chronic hemodialysis (CHD) and also evaluating the association between OCI incidence with clinical parameters and interferon lambda 3/4 (IFNL3/4) gene polymorphisms. METHODS A total of 515 patients on CHD and HCV negative markers were selected. Plus- and minus-stranded HCV-RNA was tested in peripheral blood mononuclear cell samples by reverse transcription-polymerase chain reaction and then genotyped using the restriction fragment length polymorphism method. RESULTS The frequency of OCI was 11.3% in patients on CHD. Among 58 patients with OCI, 25.8%, 62.1%, and 12.1% were infected with HCV-1a, HCV-1b, and HCV-3a, respectively. The mean alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels were 31.9 ± 24.8, 32.3 ± 19.1, and 171.6 ± 88.9, respectively. None of the patients with OCI had a history of liver disease. Multivariate logistic regression analysis indicated that cholesterol, triglyceride, low-density lipoprotein, 25-hydroxyvitamin D, platelets, duration of hemodialysis, HCV subtypes, IFNL3 rs12979860 TT, IFNL3 rs8099917 GG, IFNL3 rs12980275 GG, and IFNL4 ss469415590 ΔG/ΔG genotypes were associated with OCI. CONCLUSION There was a moderate prevalence of OCI in Iranian patients on CHD. The current study findings indicated that this infection was associated with clinical parameters and unfavorable genotypes of IFNL3 single nucleotide polymorphisms and IFNL4 ss469415590. Further studies are required to determine the correlation between OCI incidence with clinical parameters and host genetic factors.
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Affiliation(s)
- Ahmad Ayadi
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Amir Hossein Nafari
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Fatemeh Sakhaee
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
- Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran
| | - Kimia Rajabi
- Department of Microbiology, Islamic Azad University, Pharmaceutical, Sciences Branch, Tehran, Iran
| | - Yaser Ghaderi
- Islamic Azad University Central Tehran Branch, Faculty of Basic Science, Tehran, Iran
| | - Fatemeh Rahimi Jamnani
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
- Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran
| | - Farzam Vaziri
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
- Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran
| | - Seyed Davar Siadat
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
- Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran
| | - Abolfazl Fateh
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
- Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran
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Umeda N, Endo-Umeda K, Nakashima H, Kato S, Seki S, Makishima M. Frontline Science: Concanavalin A-induced acute hepatitis is attenuated in vitamin D receptor knockout mice with decreased immune cell function. J Leukoc Biol 2019; 106:791-801. [PMID: 31034649 DOI: 10.1002/jlb.3hi0219-048r] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Revised: 04/03/2019] [Accepted: 04/19/2019] [Indexed: 12/15/2022] Open
Abstract
The vitamin D receptor (VDR) is a nuclear receptor for the active form of vitamin D, 1α,25-dihydroxyvitamin D3 , and regulates various physiologic processes, such as bone and calcium metabolism, cellular proliferation and differentiation, and immunity. VDR is highly expressed in the intestine, kidney, bone, and macrophages, but is expressed at a low level in the liver. The liver is a major metabolic organ and also acts as an immune gateway for dietary nutrients and xenobiotics. In this study, we investigated the function of VDR in hepatic immune cells, such as Kupffer cells/macrophages, utilizing VDR knockout (KO) mice. We showed that VDR is functionally expressed in hepatic mononuclear cells, specifically resident Kupffer cells. We examined the role of VDR in acute hepatitis induced by concanavalin A (Con-A) and found that Con-A-induced hepatitis is attenuated in VDR-KO mice compared to wild-type (WT) mice. Con-A-induced hepatitis is known to be mediated by NKT cell activation, cytokine production, and reactive oxygen species (ROS) production in Kupffer cells/macrophages. However, the proportions of Kupffer cells/macrophages and the NKT cell activation were similar in the liver of WT and VDR-KO mice and inflammatory cytokine gene expression was increased in VDR-KO mice. On the other hand, plasma and hepatic ROS levels were decreased in the liver of VDR-KO mice compared to WT mice. The phagocytic activity of resident Kupffer cells and hepatic neutrophils were also decreased in VDR-KO mice. Therefore, VDR is necessary for Con-A-induced acute hepatitis and plays an important role in hepatic immune cell functions.
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Affiliation(s)
- Naoki Umeda
- Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan
| | - Kaori Endo-Umeda
- Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan
| | - Hiroyuki Nakashima
- Department of Immunology and Microbiology, National Defense Medical College, Tokorozawa, Saitama, Japan
| | - Shigeaki Kato
- Iwaki Meisei University, Iwaki, Fukushima, Japan.,Research Institute of Innovative Medicine, Tokiwa Foundation, Iwaki, Fukushima, Japan
| | - Shuhji Seki
- Department of Immunology and Microbiology, National Defense Medical College, Tokorozawa, Saitama, Japan
| | - Makoto Makishima
- Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan
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Barooah P, Saikia S, Bharadwaj R, Sarmah P, Bhattacharyya M, Goswami B, Medhi S. Role of VDR, GC, and CYP2R1 Polymorphisms in the Development of Hepatocellular Carcinoma in Hepatitis C Virus-Infected Patients. Genet Test Mol Biomarkers 2019; 23:325-331. [PMID: 30942619 DOI: 10.1089/gtmb.2018.0170] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Aims: This study was designed to determine if vitamin D receptor (VDR), carrier globulin/binding protein (GC), and cytochrome P-450 family 2, subfamily R, polypeptide 1 (CYP2R1) gene polymorphisms are risk factors in the development of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-infected patients from Northeast India. Materials and Methods: A total of 351 HCV-infected patients were enrolled of which 167 were diagnosed with chronic hepatitis C (CHC), 124 with liver cirrhosis (LC), and 60 with HCC together with 102 age- and sex-matched healthy controls. VDR (BsmI, ApaI, and TaqI), GC (rs4588, rs7051), and CYP2R1 (rs10741657) gene polymorphisms were genotyped for all subjects. Statistical data were analyzed using SPSS ver. 22.0. Results: The frequency of the ApaI CC genotype, ApaI C allele, and bAt haplotype of the VDR gene was significantly higher in HCC and LC patients than controls. After adjusting for other covariates (age, gender, platelet count, AST, ALT, serum albumin, and viral load) logistic regression analysis showed that the ApaI CC genotype and bAt haplotype were independent predictors of HCC development. No significant associations was found for the GC and CYP2R1 polymorphisms examined with the occurrence of HCC. Conclusions: The presence of the VDR ApaI CC genotype and bAt haplotype appear to be important indicators in the development of HCC among HCV-infected patients. Larger studies are needed to further clarify and establish this potential causal relationship.
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Affiliation(s)
- Prajjalendra Barooah
- 1 Laboratory of Molecular Virology and Oncology, Department of Bioengineering and Technology, Gauhati University Institute of Science and Technology, Gauhati University, Guwahati, India.,2 Department of Gastroenterology, Gauhati Medical College and Hospital, Guwahati, India
| | - Snigdha Saikia
- 1 Laboratory of Molecular Virology and Oncology, Department of Bioengineering and Technology, Gauhati University Institute of Science and Technology, Gauhati University, Guwahati, India.,2 Department of Gastroenterology, Gauhati Medical College and Hospital, Guwahati, India
| | - Rituraj Bharadwaj
- 1 Laboratory of Molecular Virology and Oncology, Department of Bioengineering and Technology, Gauhati University Institute of Science and Technology, Gauhati University, Guwahati, India
| | - Preeti Sarmah
- 2 Department of Gastroenterology, Gauhati Medical College and Hospital, Guwahati, India
| | - Mallika Bhattacharyya
- 2 Department of Gastroenterology, Gauhati Medical College and Hospital, Guwahati, India
| | - Bhabadev Goswami
- 2 Department of Gastroenterology, Gauhati Medical College and Hospital, Guwahati, India
| | - Subhash Medhi
- 1 Laboratory of Molecular Virology and Oncology, Department of Bioengineering and Technology, Gauhati University Institute of Science and Technology, Gauhati University, Guwahati, India
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Chronic hepatitis B virus infection is associated with decreased serum 25(OH)D concentration in non-cirrhotic patients. Clin Exp Hepatol 2019; 5:75-80. [PMID: 30915410 PMCID: PMC6431090 DOI: 10.5114/ceh.2019.83160] [Citation(s) in RCA: 3] [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: 01/24/2019] [Accepted: 02/01/2019] [Indexed: 02/06/2023] Open
Abstract
Aim of the study Recent reports provide evidence for the immunomodulatory properties of vitamin D. Decreased vitamin D levels may contribute to the progression of liver disease in hepatitis B virus (HBV) infection. This study aims to assess serum 25(OH)D in patients with chronic HBeAg-negative HBV (CHB) infection at different phases of disease. Material and methods Fifty-eighty patients with CHB, 10 with a history of HBsAg/anti-HBs seroconversion, were enrolled. The control group consisted of 9 healthy volunteers. Serum 25(OH)D concentration was assessed by ELISA. Results Serum 25(OH)D concentration was significantly lower in the CHB group in comparison to the HC group. It did not differ across the consecutive phases of the HBeAg-negative HBV infection. Negative correlations between serum 25(OH)D and alanine aminotransferase (ALT) as well as frequency of peripheral blood monocytes were observed. Serum 25(OH)D in samples collected in winter was significantly lower in comparison to the pool of samples collected in the summer. Serum 25(OH)D concentration was not associated with the phases of HBV-infection, HBV viral load, APRI or liver histology. Conclusions Serum 25(OH)D is significantly decreased in HBV infection irrespectively of the phase of the infection and negatively correlates with serum ALT level, which may reflect the deterioration of liver function. Based on our results, we can conclude that the role of vitamin D in the immune control of HBV infection is probably irrelevant.
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Gomes TL, Fernandes RC, Vieira LL, Schincaglia RM, Mota JF, Nóbrega MS, Pichard C, Pimentel GD. Low vitamin D at ICU admission is associated with cancer, infections, acute respiratory insufficiency, and liver failure. Nutrition 2018; 60:235-240. [PMID: 30682545 DOI: 10.1016/j.nut.2018.10.018] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Revised: 10/05/2018] [Accepted: 10/14/2018] [Indexed: 12/28/2022]
Abstract
OBJECTIVES Vitamin D deficiency may be associated with comorbidities and poor prognosis. However, this association in patients in the intensive care unit (ICU) has not been fully elucidated. The aim of this study was to investigate whether the serum concentrations of 25-hydroxyvitamin D (25[OH]D) within the first 48 h after ICU admission are associated with prognostic indicators (Acute Physiology and Chronic Health Evaluation [APACHE] II, Sequential Organ Failure Assessment [SOFA] score, Charlson comorbidity index [CCI]), clinical complications, serum C-reactive protein (CRP) concentrations, mechanical ventilation duration, and mortality. METHODS Seventy-one patients were admitted to the ICU, and their concentrations of 25(OH)D in the first 48 h were analyzed. To evaluate the prognostic factors in the ICU, APACHE II scores, SOFA scores, CCI questionnaires, mechanical ventilation time, CRP, and mortality were used. RESULTS The mean concentration of 25(OH)D was 17.7 ± 8.27 ng/mL (range 3.5-37.5 ng/mL), with 91.6% presenting with deficiency at admission. Although no associations were found between serum 25(OH)D concentrations with mechanical ventilation time, CRP, mortality, and APACHE II and SOFA severity scores, we found associations with the CCI when adjusted by age (model 1: odds ratio [OR], 1.64; 95% confidence interval [CI], 1.14-2.34) and by age, sex and body mass index (model 2: OR, 1.59; 95% CI, 1.10-2.34). In addition, among the comorbidities present, 25(OH)D concentrations were inversely associated with cancer (crude model OR, 3.42; 95% CI, 1.21-9.64) and liver disease (crude model OR, 9.64; 95% CI, 2.28-40.60). CONCLUSION We found a strong association between 25(OH)D concentrations and the prognostic indicator CCI and clinical complications (acute respiratory insufficiency, acute liver failure, and infections), but no associations with the prognostic indicators APACHE II and SOFA score, CRP, mechanical ventilation duration, or mortality. The main comorbidities associated with low 25(OH)D were cancer and liver disease, suggesting that the determination of 25(OH)vitamin D is relevant during the ICU stay.
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Affiliation(s)
- Tatyanne Ln Gomes
- Clinical Hospital, Empresa Brasileira de Serviços Hospitalares, Federal University of Goias, Goiânia, Brazil
| | - Renata C Fernandes
- Clinical Hospital, Empresa Brasileira de Serviços Hospitalares, Federal University of Goias, Goiânia, Brazil
| | - Liana L Vieira
- Clinical Hospital, Empresa Brasileira de Serviços Hospitalares, Federal University of Goias, Goiânia, Brazil
| | - Raquel M Schincaglia
- Clinical and Sports Nutrition Research Laboratory, Faculty of Nutrition, Federal University of Goias, Goiânia, Brazil
| | - João F Mota
- Clinical and Sports Nutrition Research Laboratory, Faculty of Nutrition, Federal University of Goias, Goiânia, Brazil
| | - Marciano S Nóbrega
- Clinical Hospital, Empresa Brasileira de Serviços Hospitalares, Federal University of Goias, Goiânia, Brazil
| | - Claude Pichard
- Clinical Nutrition, Geneva University Hospital, Geneva, Switzerland
| | - Gustavo D Pimentel
- Clinical and Sports Nutrition Research Laboratory, Faculty of Nutrition, Federal University of Goias, Goiânia, Brazil.
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Savić Ž, Vračarić V, Milić N, Nićiforović D, Damjanov D, Pellicano R, Medić-Stojanoska M, Abenavoli L. Vitamin D supplementation in patients with alcoholic liver cirrhosis: a prospective study. Minerva Med 2018; 109:352-357. [PMID: 29963831 DOI: 10.23736/s0026-4806.18.05723-3] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND The liver is involved in the metabolism of vitamin D. The prevalence of osteopenia in alcoholic liver disease (ALD) patients is 34-48%, and the prevalence of osteoporosis is 11-36%. Advanced liver disease is considered a risk factor for the development of osteoporosis. The aim of this study was to establish the relationship between vitamin D level and Child-Pugh score in patients with alcoholic liver cirrhosis (ALC), and to evaluate the effects of oral vitamin D supplementation. METHODS Seventy male ALC patients in the absence of active alcohol intake were enrolled and their clinical and laboratory data were recorded. A supplementation of cholecalciferol 1000 IU/day was administered. The vitamin D status was analyzed during the study, in patients stratified by Child-Pugh score. RESULTS The study was completed by fifty patients. At the enrollment, the mean level of vitamin D was 60.73±28.02, 50.53±39.52 and 26.71±12.81 nmol/L, respectively for Child-Pugh score class A, B and C. During vitamin D supplementation it was found in all the patients a significant increase of its levels during the first six months (P<0.05). However, in class C the improvement was consistent also after year (P<0.05). At the end of the study, two of seven patients initially in class C changed in class A, four from class C to B, and one remained in class C (P=0.012). Out of seventeen patients initially in class B, eleven changed to class A, and six remained in class B. CONCLUSIONS In patients with ALC, higher level of vitamin D level is related with lower Child-Pugh score. The supplementation of 1000 IU/day of vitamin D in these patients was optimal for a period of at least six months. A decrease in the Child-Pugh score was also found, with a redistribution of the patients in different classes.
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Affiliation(s)
- Željka Savić
- Clinic of Gastroenterology and Hepatology, Clinical Center of Vojvodina, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
| | - Vladimir Vračarić
- Clinic of Gastroenterology and Hepatology, Clinical Center of Vojvodina, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
| | - Nataša Milić
- Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
| | - Dijana Nićiforović
- Clinic of Radiology, Clinical Center of Vojvodina, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
| | - Dragomir Damjanov
- Clinic of Gastroenterology and Hepatology, Clinical Center of Vojvodina, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
| | | | - Milica Medić-Stojanoska
- Clinic for Endocrinology, Diabetes, and Metabolic Diseases, Clinical Center of Vojvodina, University of Novi Sad, Novi Sad, Serbia
| | - Ludovico Abenavoli
- Department of Health Sciences, Magna Græcia University, Catanzaro, Italy -
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