|
1
|
Wang P, Chen J, Li Z, Xiong H, Lei Z, Chen D, Zhang Y, Gao Z, Mo Z. Association of vitamin D with functional cure in chronic hepatitis B: Insights from a retrospective cohort study and an intervention study. Clin Nutr ESPEN 2024; 64:244-252. [PMID: 39423925 DOI: 10.1016/j.clnesp.2024.10.145] [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: 12/10/2023] [Revised: 09/19/2024] [Accepted: 10/13/2024] [Indexed: 10/21/2024]
Abstract
BACKGROUND & AIM Functional cure for chronic hepatitis B (CHB) patients can be achieved using nucleos(t)ide analogues (NAs) and pegylated interferon alpha (Peg-IFNα) combination treatment. However, the role of vitamin D in functional cure remains unclear. We aimed to investigate the association between vitamin D levels and functional cure in CHB patients. METHODS A retrospective study was conducted to detect changes in serum 25-hydroxyvitamin D (25(OH)D) levels in 526 CHB patients. Furthermore, an intervention study was conducted on 90 CHB patients with baseline vitamin D insufficiency, and 45 patients were randomly assigned to the control group receiving NAs/Peg-IFNα treatment, whereas the remaining patients were categorized into the vitamin D group (VD group) receiving NAs/Peg-IFNα treatment combined with vitamin D supplementation at 800 IU/day. RESULTS A retrospective study revealed a progressive elevation in serum 25(OH)D levels throughout the duration of treatment. The cured group displayed significantly higher serum 25(OH)D levels than the uncured group (P = 0.046) at the end of treatment, and the changes in serum 25(OH)D (Δ25(OH)D) levels between the two groups were found to be significantly different (P < 0.0001). In the intervention study, the VD group tended to have an increased functional cure rate (48.0 %) compared with the control group (34.3 %) in the binary logistic regression equation analysis (P = 0.09). Notably, a linear mixed-effects model in the longitudinal analysis indicated a significant impact of serum 25(OH)D levels on treatment outcomes (P = 0.017). CONCLUSIONS Serum 25(OH)D and Δ25(OH)D were both positively associated with functional cure in this retrospective study, and vitamin D supplementation may be helpful for functional cure in CHB patients. REGISTRATION NUMBER OF CLINICAL TRIAL ChiCTR1800020108.
Collapse
Affiliation(s)
- Peipei Wang
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China; Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China; Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong 510080, China
| | - Junjian Chen
- Institute of Human Virology, Zhongshan School of Medicine (Sun Yat-sen University), No. 74, Zhong Shan II Rd, Guangzhou 510080, China; Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong 510080, China
| | - Zhipeng Li
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China; Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China; Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong 510080, China
| | - Husheng Xiong
- Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China
| | - Ziying Lei
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China; Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China; Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong 510080, China
| | - Dabiao Chen
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China; Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China; Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong 510080, China
| | - Ying Zhang
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China; Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China; Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong 510080, China.
| | - Zhiliang Gao
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China; Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China; Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong 510080, China.
| | - Zhishuo Mo
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China; Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China; Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong 510080, China.
| |
Collapse
|
|
2
|
Oliveira KKDS, Torres DJL, Barros MDS, Rafael Moreira L, Junior CDDS, Soares AKDA, de Albuquerque MDPCR, Cavalcante MDGAM, Junior WADO, Rabello MCDS, de Lorena VMB. Vitamin D treatment distinctly modulates cytokine production by peripheral blood mononuclear cells among patients with chronic cardiac and indeterminate clinical forms of Chagas disease. Immun Inflamm Dis 2024; 12:e1330. [PMID: 39267468 PMCID: PMC11393450 DOI: 10.1002/iid3.1330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 06/17/2024] [Accepted: 06/18/2024] [Indexed: 09/17/2024] Open
Abstract
INTRODUCTION Chagas disease is caused by the protozoan Trypanosoma cruzi and is clinically divided into acute and chronic phases. Chronic Chagas cardiomyopathy is the most studied manifestation of the disease. Vitamin D deficiency has been suggested as a risk factor for cardiovascular disease. No studies demonstrate the action of this hormone in the cells of patients with chronic Chagas heart disease. OBJECTIVE To evaluate the in vitro immunomodulatory effect of vitamin D on peripheral blood mononuclear cells of patients with the different chronic clinical forms of Chagas disease. Evaluating vitamin D's in vitro effect on blood cells by producing cytokines. METHODS Thirteen patients of the undetermined form (IND), 13 of the mild cardiac form (CARD1) and 14 of the severe cardiac form (CARD2) of Chagas disease, and 12 with idiopathic heart disease (CARDid) were included. The cells obtained from peripheral blood were treated in vitro with vitamin D (1 × 10-7 M) for 24 h and cytokines were dosed in the culture supernatant. RESULTS Although it was not possible to demonstrate statistically significant differences between the groups studied, our data showed that the cells treated with vitamin D modify (p < .05) the production of interferon-γ (IFN-γ) (decrease in IND), tumor necrosis factor-α (TNF-α) (decreased in CARD1 and CARDid), interleukin (IL)-6 (increased in all groups), and IL-10 (decreased in CARD1, CARD2, and CARDid) when compared to untreated cells. CONCLUSION In vitro treatment with vitamin D distinctly modulated the production of cytokines by mononuclear cells of peripheral blood among patients with chronic and indeterminate cardiac clinical forms of Chagas disease.
Collapse
Affiliation(s)
| | - Diego José Lira Torres
- Institute Aggeu Magalhães, Laboratory of ImmunoparasitologyOswaldo Cruz Foundation‐FIOCRUZRecifePernambucoBrazil
- Tropical Medicine DepartmentFederal University of Pernambuco (UFPE)RecifePernambucoBrazil
| | - Michelle da Silva Barros
- Institute Aggeu Magalhães, Laboratory of ImmunoparasitologyOswaldo Cruz Foundation‐FIOCRUZRecifePernambucoBrazil
| | - Leyllane Rafael Moreira
- Institute Aggeu Magalhães, Laboratory of ImmunoparasitologyOswaldo Cruz Foundation‐FIOCRUZRecifePernambucoBrazil
- Tropical Medicine DepartmentFederal University of Pernambuco (UFPE)RecifePernambucoBrazil
| | - Claudeir Dias da Silva Junior
- Institute Aggeu Magalhães, Laboratory of ImmunoparasitologyOswaldo Cruz Foundation‐FIOCRUZRecifePernambucoBrazil
- Tropical Medicine DepartmentFederal University of Pernambuco (UFPE)RecifePernambucoBrazil
| | | | | | | | - Wilson Alves de Oliveira Junior
- Chagas disease and Heart Failure Outpatient Clinic of the Pronto Socorro Cardiológico de PernambucoUniversity of Pernambuco (UPE)RecifePernambucoBrazil
| | | | - Virginia Maria Barros de Lorena
- Institute Aggeu Magalhães, Laboratory of ImmunoparasitologyOswaldo Cruz Foundation‐FIOCRUZRecifePernambucoBrazil
- Tropical Medicine DepartmentFederal University of Pernambuco (UFPE)RecifePernambucoBrazil
| |
Collapse
|
|
3
|
Aggeletopoulou I, Tsounis EP, Triantos C. Vitamin D and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Novel Mechanistic Insights. Int J Mol Sci 2024; 25:4901. [PMID: 38732118 PMCID: PMC11084591 DOI: 10.3390/ijms25094901] [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: 03/15/2024] [Revised: 04/23/2024] [Accepted: 04/29/2024] [Indexed: 05/13/2024] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasingly prevalent condition characterized by abnormal fat accumulation in the liver, often associated with metabolic disorders. Emerging evidence suggests a potential link between vitamin D deficiency and the development and progression of MASLD. The current review provides a concise overview of recent studies uncovering novel mechanistic insights into the interplay between vitamin D and MASLD. Several epidemiological studies have highlighted a significant association between low vitamin D levels and an increased risk of MASLD. Vitamin D, traditionally known for its role in bone health, has now been recognized as a key player in various physiological processes, including immune regulation and inflammation. Experimental studies using animal models have demonstrated that vitamin D deficiency exacerbates liver steatosis and inflammation, suggesting a potential protective role against MASLD. Mechanistically, vitamin D appears to modulate MASLD through multiple pathways. Firstly, the vitamin D receptor (VDR) is abundantly expressed in liver cells, indicating a direct regulatory role in hepatic function. Activation of the VDR has been shown to suppress hepatic lipid accumulation and inflammation, providing a mechanistic basis for the observed protective effects. Additionally, vitamin D influences insulin sensitivity, a critical factor in MASLD pathogenesis. Improved insulin sensitivity may mitigate the excessive accumulation of fat in the liver, thus attenuating MASLD progression. In parallel, vitamin D exhibits anti-inflammatory properties by inhibiting pro-inflammatory cytokines implicated in MASLD pathophysiology. Experimental evidence suggests that the immunomodulatory effects of vitamin D extend to the liver, reducing inflammation and oxidative stress, key drivers of MASLD, and the likelihood of hepatocyte injury and fibrosis. Understanding the complex interplay between vitamin D and MASLD provides a basis for exploring targeted therapeutic strategies and preventive interventions. As vitamin D deficiency is a modifiable risk factor, addressing this nutritional concern may prove beneficial in mitigating the burden of MASLD and associated metabolic disorders.
Collapse
Affiliation(s)
| | | | - Christos Triantos
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, 26504 Patras, Greece; (I.A.); (E.P.T.)
| |
Collapse
|
|
4
|
Pop TL, Sîrbe C, Benţa G, Mititelu A, Grama A. The Role of Vitamin D and Vitamin D Binding Protein in Chronic Liver Diseases. Int J Mol Sci 2022; 23:ijms231810705. [PMID: 36142636 PMCID: PMC9503777 DOI: 10.3390/ijms231810705] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 09/09/2022] [Accepted: 09/12/2022] [Indexed: 11/24/2022] Open
Abstract
Vitamin D (calciferol) is a fat-soluble vitamin that has a significant role in phospho-calcium metabolism, maintaining normal calcium levels and bone health development. The most important compounds of vitamin D are cholecalciferol (vitamin D3, or VD3) and ergocalciferol (vitamin D2, or VD2). Besides its major role in maintaining an adequate level of calcium and phosphate concentrations, vitamin D is involved in cell growth and differentiation and immune function. Recently, the association between vitamin D deficiency and the progression of fibrosis in chronic liver disease (CLD) was confirmed, given the hepatic activation process and high prevalence of vitamin D deficiency in these diseases. There are reports of vitamin D deficiency in CLD regardless of the etiology (chronic viral hepatitis, alcoholic cirrhosis, non-alcoholic fatty liver disease, primary biliary cirrhosis, or autoimmune hepatitis). Vitamin D binding protein (VDBP) is synthesized by the liver and has the role of binding and transporting vitamin D and its metabolites to the target organs. VDBP also plays an important role in inflammatory response secondary to tissue damage, being involved in the degradation of actin. As intense research during the last decades revealed the possible role of vitamin D in liver diseases, a deeper understanding of the vitamin D, vitamin D receptors (VDRs), and VDBP involvement in liver inflammation and fibrogenesis could represent the basis for the development of new strategies for diagnosis, prognosis, and treatment of liver diseases. This narrative review presents an overview of the evidence of the role of vitamin D and VDBP in CLD, both at the experimental and clinical levels.
Collapse
Affiliation(s)
- Tudor Lucian Pop
- 2nd Pediatric Discipline, Department of Mother and Child, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
- 2nd Pediatric Clinic, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania
| | - Claudia Sîrbe
- 2nd Pediatric Discipline, Department of Mother and Child, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
- Correspondence:
| | - Gabriel Benţa
- 2nd Pediatric Discipline, Department of Mother and Child, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Alexandra Mititelu
- 2nd Pediatric Discipline, Department of Mother and Child, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Alina Grama
- 2nd Pediatric Discipline, Department of Mother and Child, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
- 2nd Pediatric Clinic, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania
| |
Collapse
|
|
5
|
Liu D, Meng X, Tian Q, Cao W, Fan X, Wu L, Song M, Meng Q, Wang W, Wang Y. Vitamin D and Multiple Health Outcomes: An Umbrella Review of Observational Studies, Randomized Controlled Trials, and Mendelian Randomization Studies. Adv Nutr 2022; 13:1044-1062. [PMID: 34999745 PMCID: PMC9340982 DOI: 10.1093/advances/nmab142] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Revised: 12/29/2020] [Accepted: 11/19/2021] [Indexed: 12/18/2022] Open
Abstract
Observational studies, randomized controlled trials (RCTs), and Mendelian randomization (MR) studies have yielded inconsistent results on the associations of vitamin D concentrations with multiple health outcomes. In the present umbrella review we aimed to evaluate the effects of low vitamin D concentrations and vitamin D supplementation on multiple health outcomes. We summarized current evidence obtained from meta-analyses of observational studies that examined associations between vitamin D concentrations and multiple health outcomes, meta-analyses of RCTs that investigated the effect of vitamin D supplementation on multiple health outcomes, and MR studies that explored the causal associations of vitamin D concentrations with various diseases (international prospective register of systematic reviews PROSPERO registration number CRD42018091434). A total of 296 meta-analyses of observational studies comprising 111 unique outcomes, 139 meta-analyses of RCTs comprising 46 unique outcomes, and 73 MR studies comprising 43 unique outcomes were included in the present umbrella review. Twenty-eight disease outcomes were identified by both meta-analyses of observational studies and MR studies. Seventeen of these reported disease outcomes had consistent results, demonstrating that lower concentrations of vitamin D were associated with a higher risk for all-cause mortality, Alzheimer's disease, hypertension, schizophrenia, and type 2 diabetes. The combinations of consistent evidence obtained by meta-analyses of observational studies and MR studies together with meta-analyses of RCTs showed that vitamin D supplementation was associated with a decreased risk for all-cause mortality but not associated with the risk for Alzheimer's disease, hypertension, schizophrenia, or type 2 diabetes. The results indicated that vitamin D supplementation is a promising strategy with long-term preventive effects on multiple chronic diseases and thus has the potential to decrease all-cause mortality. However, the current vitamin D supplementation strategy might not be an efficient intervention approach for these diseases, suggesting that new strategies are highly needed to improve the intervention outcomes.
Collapse
Affiliation(s)
- Di Liu
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China
- Centre for Biomedical Information Technology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China
| | - Xiaoni Meng
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China
| | - Qiuyue Tian
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China
| | - Weijie Cao
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China
| | - Xin Fan
- School of Basic Medical Sciences, Capital Medical University, Beijing, China
| | - Lijuan Wu
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China
| | - Manshu Song
- Centre for Precision Health, School of Medical and Health Sciences, Edith Cowan University, Perth, WA, Australia
| | - Qun Meng
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China
| | - Wei Wang
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China
- Centre for Precision Health, School of Medical and Health Sciences, Edith Cowan University, Perth, WA, Australia
- School of Public Health, Shandong First Medical University and Shandong Academy of Medical Science, Tai'an, Shandong, China
| | - Youxin Wang
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China
- Centre for Precision Health, School of Medical and Health Sciences, Edith Cowan University, Perth, WA, Australia
| |
Collapse
|
|
6
|
Aggeletopoulou I, Thomopoulos K, Mouzaki A, Triantos C. Vitamin D–VDR Novel Anti-Inflammatory Molecules—New Insights into Their Effects on Liver Diseases. Int J Mol Sci 2022; 23:ijms23158465. [PMID: 35955597 PMCID: PMC9369388 DOI: 10.3390/ijms23158465] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 07/26/2022] [Accepted: 07/28/2022] [Indexed: 02/05/2023] Open
Abstract
There is consistent evidence that vitamin D deficiency is strongly associated with liver dysfunction, disease severity, and poor prognosis in patients with liver disease. Vitamin D and its receptor (VDR) contribute to the regulation of innate and adaptive immune responses. The presence of genetic variants of vitamin D- and VDR-associated genes has been associated with liver disease progression. In our recent work, we summarized the progress in understanding the molecular mechanisms involved in vitamin D–VDR signaling and discussed the functional significance of VDR signaling in specific cell populations in liver disease. The current review focuses on the complex interaction between immune and liver cells in the maintenance of liver homeostasis and the development of liver injury, the interplay of vitamin D and VDR in the development and outcome of liver disease, the role of vitamin D- and VDR-associated genetic variants in modulating the occurrence and severity of liver disease, and the therapeutic value of vitamin D supplementation in various liver diseases. The association of the vitamin D–VDR complex with liver dysfunction shows great potential for clinical application and supports its use as a prognostic index and diagnostic tool.
Collapse
Affiliation(s)
- Ioanna Aggeletopoulou
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, GR-26504 Patras, Greece; (I.A.); (C.T.)
- Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, GR-26504 Patras, Greece;
| | - Konstantinos Thomopoulos
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, GR-26504 Patras, Greece; (I.A.); (C.T.)
- Correspondence:
| | - Athanasia Mouzaki
- Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, GR-26504 Patras, Greece;
| | - Christos Triantos
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, GR-26504 Patras, Greece; (I.A.); (C.T.)
| |
Collapse
|
|
7
|
Fox R, Stenning K, Slee A, Macnaughtan J, Davies N. Sarcopenia in liver cirrhosis: Prevalence, pathophysiology and therapeutic strategies. Anal Biochem 2022; 647:114581. [PMID: 35134388 DOI: 10.1016/j.ab.2022.114581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Accepted: 01/31/2022] [Indexed: 11/01/2022]
|
|
8
|
Alam W, Ullah H, Santarcangelo C, Di Minno A, Khan H, Daglia M, Arciola CR. Micronutrient Food Supplements in Patients with Gastro-Intestinal and Hepatic Cancers. Int J Mol Sci 2021; 22:8014. [PMID: 34360782 PMCID: PMC8347237 DOI: 10.3390/ijms22158014] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 07/15/2021] [Accepted: 07/18/2021] [Indexed: 02/05/2023] Open
Abstract
Colorectal carcinogenesis is the second most common cause of mortality across all types of malignancies, followed by hepatic and stomach cancers. Chemotherapy and radiotherapy are key approaches to treating cancer patients, but these carry major concerns, such as a high risk of side effects, poor accessibility, and the non-selective nature of chemotherapeutics. A number of natural products have been identified as countering various forms of cancer with fewer side effects. The potential impact of vitamins and minerals on long-term health, cognition, healthy development, bone formation, and aging has been supported by experimental and epidemiological studies. Successful treatment may thus be highly influenced by the nutritional status of patients. An insufficient diet could lead to detrimental effects on immune status and tolerance to treatment, affecting the ability of chemotherapy to destroy cancerous cells. In recent decades, most cancer patients have been taking vitamins and minerals to improve standard therapy and/or to decrease the undesirable side effects of the treatment together with the underlying disease. On the other hand, taking dietary supplements during cancer therapy may affect the effectiveness of chemotherapy. Thus, micronutrients in complementary oncology must be selected appropriately and should be taken at the right time. Here, the potential impact of micronutrients on gastro-intestinal and hepatic cancers is explored and their molecular targets are laid down.
Collapse
Affiliation(s)
- Waqas Alam
- Department of Pharmacy, Abdul Wali Khan University, Mardan 23200, Pakistan; (W.A.); (H.K.)
| | - Hammad Ullah
- Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy; (H.U.); (C.S.); (A.D.M.)
| | - Cristina Santarcangelo
- Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy; (H.U.); (C.S.); (A.D.M.)
| | - Alessandro Di Minno
- Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy; (H.U.); (C.S.); (A.D.M.)
- CEINGE-Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Naples, Italy
| | - Haroon Khan
- Department of Pharmacy, Abdul Wali Khan University, Mardan 23200, Pakistan; (W.A.); (H.K.)
| | - Maria Daglia
- Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy; (H.U.); (C.S.); (A.D.M.)
- International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China
| | - Carla Renata Arciola
- Laboratorio di Patologia delle Infezioni Associate all’Impianto, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Via San Giacomo 14, 40136 Bologna, Italy
| |
Collapse
|
|
9
|
Wu J, Lin S, Liu S, Wan B, Lin Y, Wang M, Zhu Y. The association between vitamin D-related gene polymorphisms and hepatitis B virus-related liver cirrhosis. J Int Med Res 2021; 48:300060520910906. [PMID: 32264749 PMCID: PMC7144674 DOI: 10.1177/0300060520910906] [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] [Indexed: 12/14/2022] Open
Abstract
Objectives To investigate the relationship between vitamin D-related gene single nucleotide polymorphisms (SNPs) and hepatitis B-related liver cirrhosis. Methods This study included patients with chronic hepatitis B who were admitted to the Liver Research Center of the First Affiliated Hospital of Fujian Medical University from July 2012 to August 2016. SNPs rs1544410 and rs2228570 in the vitamin D receptor gene and rs2282679 in the vitamin D-binding protein gene were detected using the imLDR™ multiple SNP typing kit. Genotype and allele frequencies were compared between groups using the chi-square test or Fisher’s exact test. Results A total of 226 patients with hepatitis B virus (HBV) infection were enrolled, including 116 with HBV-related cirrhosis and 110 patients without. The distributions of vitamin D-related gene SNPs in both groups were in accordance with the Hardy–Weinberg equilibrium. There was no significant difference in the frequency or allelic distributions of rs1544410, rs2228570, and rs2282679 between the two groups. Additionally, the SNPs were not associated with the severity of cirrhosis. Conclusion No significant connection was identified between vitamin D-related SNPs and HBV-related liver cirrhosis.
Collapse
Affiliation(s)
- Jiali Wu
- Liver Research Center of the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Su Lin
- Liver Research Center of the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Shiying Liu
- Liver Research Center of the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Bo Wan
- Faculty of Life Science and Medicine, King's College, London, UK
| | - Yehong Lin
- Liver Research Center of the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Mingfang Wang
- Liver Research Center of the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Yueyong Zhu
- Liver Research Center of the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| |
Collapse
|
|
10
|
Jeong JY, Jun DW, Park SJ, Sohn JH, Kim SG, Lee SW, Jeong SW, Kim MY, Kim W, Shim JJ, Kim HS, Suk KT, Ahn SB. Effects of vitamin D supplements in patients with chronic hepatitis C: a randomized, multi-center, open label study. Korean J Intern Med 2020; 35:1074-1083. [PMID: 31710801 PMCID: PMC7487303 DOI: 10.3904/kjim.2018.273] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Accepted: 11/05/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND/AIMS We aimed to assess the role of vitamin D supplementation in the response to pegylated interferon-α (PEG-IFN-α) plus ribavirin (RBV) treatment in patients with chronic hepatitis C (CHC). METHODS Our study was a multi-center, randomized controlled trial in 11 hospitals. CHC patients were randomly assigned (1:1) to two groups namely, PEGIFN-α plus RBV (control group) or PEG-IFN-α plus RBV + vitamin D (800 IU daily) (vitamin D group). The primary end-point was the rate of sustained virologic response (SVR). RESULTS One hundred forty eight CHC patients were randomly assigned to two groups. Seventy-one patients received the PEG-IFN-α plus RBV and 77 patients received the PEG-IFN-α plus RBV + vitamin D. A total of 105 patients completed the study (control group, 47 vs. vitamin D group, 58). Baseline characteristics were mostly similar in both the groups. There was a modest but non-significant increase in SVR in the vitamin D group compared to the control group with the intention to treat analysis (64.0% vs. 49.3 %, p = 0.071) as well as in the per protocol analysis (control group vs. vitamin D group: 74.5% vs. 84.5%, p = 0.202). Fifty-two patients (73.2%) in the control group and 63 patients (81.8%) in the vitamin D group experienced at least one adverse event. The drop-out rate due to adverse effects was not different between both groups (control group vs. vitamin D group: 19.7% vs. 10.4%, p = 0.111). CONCLUSION Vitamin D supplement did not increase SVR in treatment naïve patients with CHC irrespective of genotype.
Collapse
Affiliation(s)
- Jae Yoon Jeong
- Department of Internal Medicine, Hanyang University Guri Hospital, Guri, Korea
| | - Dae Won Jun
- Department of Internal Medicine, Hanyang University Hospital, Seoul, Korea
- Correspondence to Dae Won Jun, M.D. Department of Internal Medicine, Hanyang University College of Medicine, 222-1 Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea. Tel: +82-2-2290-8338, Fax: +82-2-972-0068, E-mail:
| | - Sol Ji Park
- Department of Clinical Pharmacology, Sungkyunkwan University, Seoul, Korea
| | - Joo Hyun Sohn
- Department of Internal Medicine, Hanyang University Guri Hospital, Guri, Korea
| | - Sang Gyune Kim
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Se Whan Lee
- Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Korea
| | - Soung Won Jeong
- Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea
| | - Moon Young Kim
- Department of Internal Medicine, Yonsei University Wonju Severance Christian Hospital, Wonju, Korea
| | - Won Kim
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Jae-Jun Shim
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea
| | - Hyoung Su Kim
- Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Korea
| | - Ki Tae Suk
- Department of Internal Medicine, Hallym University Chuncheon Sacred Heart Hospital, Chuncheon, Korea
| | - Sang Bong Ahn
- Department of Internal Medicine, Eulji University School of Medicine, Seoul, Korea
| |
Collapse
|
|
11
|
Relationship Between 25-HydroxyVitamin D Level and Liver Stiffness in Patients with Chronic Hepatitis B Using Transient Elastography. HEPATITIS MONTHLY 2020. [DOI: 10.5812/hepatmon.100891] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
Background: Studies are limited on the relationship between vitamin D levels and liver fibrosis in patients with hepatitis B. Objectives: A study was conducted to investigate the relationship between 25-hydroxyvitamin D levels and liver stiffness in patients with hepatitis B. Methods: In a cross-sectional study, serum 25-hydroxyvitamin D levels and liver stiffness, measured by transient elastography (TE), were evaluated in 281 patients with hepatitis B. The predictors of liver stiffness and its relationship with 25-hydroxyvitamin D level, coinfection with hepatitis D, age, and viral load were determined using multivariate analysis. Results: A significant correlation was observed between 25-hydroxyvitamin D deficiency and liver stiffness. Based on multivariate analysis, factors that were independently associated with advanced liver fibrosis included vitamin D level (P < 0.001), coinfection with hepatitis D (P < 0.001), and age (P < 0.001). Among 281 patients, the frequency of vitamin D deficiency (< 10 ng/mL), insufficiency (≥ 10 and < 20 ng/mL), and adequacy (≥ 30 ng/mL) was 40 (14.2%), 150 (53.4%), and 91 (32.4%), respectively. Conclusions: In hepatitis B patients, vitamin D deficiency was independently associated with advanced liver fibrosis. An increase in age and coinfection with hepatitis D were also directly related to liver stiffness.
Collapse
|
|
12
|
Udomsinprasert W, Jittikoon J, Sukkho S, Pojarassangkul N, Sangroongruangsri S, Chaikledkaew U. Decreased circulating vitamin D reflects adverse outcomes of hepatitis C virus infection: A systematic review and meta-analysis. J Infect 2020; 81:585-599. [PMID: 32553842 DOI: 10.1016/j.jinf.2020.06.025] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Revised: 05/21/2020] [Accepted: 06/12/2020] [Indexed: 02/07/2023]
Abstract
OBJECTIVES This study aimed to clarify associations of circulating vitamin D and its status with severity of HCV infection. METHODS We performed systemic literature search in PubMed, Scopus, and Cochrane library databases from inception until the end of December 2019 with terms related to vitamin D and hepatitis C. RESULTS A total of 28 studies consisting of 7736 HCV-infected patients and 14061 control subjects without liver diseases were included. Compared to controls, circulating vitamin D levels were significantly lessened in HCV-infected patients (mean difference, MD=-14.15, 95% CI: -20.51 to -7.80). Remarkably decreased circulating vitamin D was found in the patients with severe fibrosis (MD=-3.38, 95% CI: -4.51 to -2.25), non-achieving SVR (MD=-2.99, 95%CI: -5.55 to -0.42), and advanced inflammation (MD=-4.68, 95% CI: -8.50 to -0.86). Low vitamin D status (<20 ng/mL) was significantly associated with increased odds of HCV infection (pooled OR=2.41, 95% CI: 1.48 to 3.95). Besides, HCV-infected patients with low vitamin D status showed significantly escalated odds of severe fibrosis and non-achieving SVR (pooled OR=1.70, 95% CI: 1.27 to 2.26; pooled OR=2.04, 95% CI: 1.62 to 2.57, respectively). CONCLUSION HCV-infected patients with declined circulating vitamin D levels were associated with severe fibrosis, non-achieving SVR, and advanced inflammation.
Collapse
Affiliation(s)
- Wanvisa Udomsinprasert
- Department of Biochemistry, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayudhaya Road, Rajathevi, Bangkok 10400, Thailand.
| | - Jiraphun Jittikoon
- Department of Biochemistry, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayudhaya Road, Rajathevi, Bangkok 10400, Thailand.
| | - Sorraya Sukkho
- Department of Biochemistry, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayudhaya Road, Rajathevi, Bangkok 10400, Thailand.
| | - Nicha Pojarassangkul
- Department of Biochemistry, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayudhaya Road, Rajathevi, Bangkok 10400, Thailand.
| | - Sermsiri Sangroongruangsri
- Social and Administrative Pharmacy Division, Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.
| | - Usa Chaikledkaew
- Social and Administrative Pharmacy Division, Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand; Mahidol University Health Technology Assessment (MUHTA) Graduate Program, Bangkok 10400, Thailand.
| |
Collapse
|
|
13
|
Kim TH, Yun SG, Choi J, Goh HG, Lee HA, Yim SY, Choi SJ, Lee YS, Yoon EL, Jung YK, Seo YS, Kim JH, Yim HJ, Yeon JE, Byun KS, Um SH. Differential Impact of Serum 25-Hydroxyvitamin D3 Levels on the Prognosis of Patients with Liver Cirrhosis According to MELD and Child-Pugh Scores. J Korean Med Sci 2020; 35:e129. [PMID: 32419396 PMCID: PMC7234861 DOI: 10.3346/jkms.2020.35.e129] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Accepted: 03/03/2020] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Prognosis of patients with diverse chronic diseases is reportedly associated with 25-hydroxyvitamin D levels. In this study, we investigated the potential role of 25-hydroxyvitamin D3 (25[OH]D3) levels in improving the predictive power of conventional prognostic models for patients with liver cirrhosis. METHODS We investigated clinical findings, including serum 25(OH)D3 levels at admission, of 155 patients with cirrhosis who were followed up for a median of 16.9 months. RESULTS Median 25(OH)D3 levels were significantly different among patients exhibiting Child-Pugh grades A, B, and C. Mortality, including urgent transplantation, was significantly associated with 25(OH)D3 levels in univariate analysis. Severe vitamin-D deficiency (serum 25[OH]D3 level < 5.0 ng/mL) was significantly related to increased mortality, even after adjusting for Child-Pugh and Model for End-stage Liver Disease (MELD) scores. In particular, the presence of severe vitamin D deficiency clearly defined a subgroup with significantly poorer survival among patients with Child-Pugh scores of 5-10 or MELD scores ≤ 20. A new combination model of MELD score and severe vitamin D deficiency showed significantly more accurate predictive power for short- and long-term mortality than MELD scores alone. Additionally, serum 25(OH)D3 levels and new model scores were significantly associated with the development of spontaneous bacterial peritonitis, overt encephalopathy, and acute kidney injury. CONCLUSION Serum 25(OH)D3 level is an independent prognostic factor for patients with liver cirrhosis and has a differential impact on disease outcomes according to MELD and Child-Pugh scores.
Collapse
Affiliation(s)
- Tae Hyung Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Seung Gyu Yun
- Department of Laboratory Medicine, Korea University College of Medicine, Seoul, Korea
| | - Jimi Choi
- Department of Biostatistics, Korea University College of Medicine, Seoul, Korea
| | - Hyun Gil Goh
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Han Ah Lee
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Sun Young Yim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Seong Ji Choi
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Young Sun Lee
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Eileen L Yoon
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Young Kul Jung
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Yeon Seok Seo
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Ji Hoon Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Hyung Joon Yim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Jong Eun Yeon
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Kwan Soo Byun
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Soon Ho Um
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
| |
Collapse
|
|
14
|
Lee C. Controversial Effects of Vitamin D and Related Genes on Viral Infections, Pathogenesis, and Treatment Outcomes. Nutrients 2020; 12:nu12040962. [PMID: 32235600 PMCID: PMC7230640 DOI: 10.3390/nu12040962] [Citation(s) in RCA: 24] [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: 02/29/2020] [Revised: 03/23/2020] [Accepted: 03/26/2020] [Indexed: 12/11/2022] Open
Abstract
Vitamin D (VD) plays an essential role in mineral homeostasis and bone remodeling. A number of different VD-related genes (VDRG) are required for the metabolic activation of VD and the subsequent induction of its target genes. They include a set of genes that encode for VD-binding protein, metabolic enzymes, and the VD receptor. In addition to its well-characterized skeletal function, the immunoregulatory activities of VD and the related polymorphisms of VDRG have been reported and linked to its therapeutic and preventive actions for the control of several viral diseases. However, in regards to their roles in the progression of viral diseases, inconsistent and, in some cases, contradictory results also exist. To resolve this discrepancy, I conducted an extensive literature search by using relevant keywords on the PubMed website. Based on the volume of hit papers related to a certain viral infection, I summarized and compared the effects of VD and VDRG polymorphism on the infection, pathogenesis, and treatment outcomes of clinically important viral diseases. They include viral hepatitis, respiratory viral infections, acquired immunodeficiency syndrome (AIDS), and other viral diseases, which are caused by herpesviruses, dengue virus, rotavirus, and human papillomavirus. This review will provide the most current information on the nutritional and clinical utilization of VD and VDRG in the management of the key viral diseases. This information should be valuable not only to nutritionists but also to clinicians who wish to provide evidence-based recommendations on the use of VD to virally infected patients.
Collapse
Affiliation(s)
- Choongho Lee
- College of Pharmacy, Dongguk University, Goyang 10326, Korea
| |
Collapse
|
|
15
|
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.
Collapse
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.
| |
Collapse
|
|
16
|
Kozeniecki M, Ludke R, Kerner J, Patterson B. Micronutrients in Liver Disease: Roles, Risk Factors for Deficiency, and Recommendations for Supplementation. Nutr Clin Pract 2019; 35:50-62. [PMID: 31840874 DOI: 10.1002/ncp.10451] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Micronutrients are essential components of the diet and are required to maintain fundamental bodily functions. Liver disease has a profound effect on nutrient intake, metabolism of nutrients, and nutrition status, often resulting in some degree of malnutrition, including micronutrient deficiency. Vitamin and mineral deficiencies can impair metabolic processes at the cellular and biochemical level even before clinical and physical alterations are seen. It is essential that micronutrient status is evaluated as part of a comprehensive nutrition assessment for all patients with chronic or advanced liver disease. Early intervention to correct suspected or confirmed deficiencies may minimize symptoms and improve clinical outcomes and quality of life. In this narrative review, different types of liver disease and associated micronutrient abnormalities are outlined, and methods of micronutrient assessment and supplementation are discussed.
Collapse
Affiliation(s)
- Michelle Kozeniecki
- Department of Nutrition Services, Froedtert Hospital, Milwaukee, Wisconsin, USA
| | - Rachel Ludke
- Department of Nutrition Services, Froedtert Hospital, Milwaukee, Wisconsin, USA
| | - Jennifer Kerner
- Transplant Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
| | - Brittney Patterson
- Clinical Nutrition Department, Stanford Health Care, Stanford, California, USA
| |
Collapse
|
|
17
|
Yang JJ, Fan HZ, Tian T, Wu MP, Xie CN, Huang P, Yu RB, Yi HG, Zhang Y, Wang J. Impact of CYP2R1, CYP27A1 and CYP27B1 genetic polymorphisms controlling vitamin D metabolism on susceptibility to hepatitis C virus infection in a high-risk Chinese population. Arch Virol 2019; 164:2909-2918. [PMID: 31520221 DOI: 10.1007/s00705-019-04378-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Accepted: 07/17/2019] [Indexed: 12/21/2022]
Abstract
CYP27A1, CYP2R1 and CYP27B1 hydroxylases are involved in the synthesis of 1, 25-hydroxyvitamin D3, which plays a role in the immune regulation and pathogenesis of hepatitis C virus (HCV) infection. The aim of the present study was to investigate the relationships between polymorphisms in vitamin D pathway genes and HCV infection outcomes in a Chinese population. Nine single-nucleotide polymorphisms (SNPs) of CYP27A1, CYP2R1 and CYP27B1 were genotyped in a high-risk Chinese population. The distributions of these SNPs were compared among groups with different outcomes of HCV infection, including 863 cases of persistent HCV infection, 524 cases of spontaneous clearance, and 1079 uninfected controls. The results showed that the CYP2R1 rs12794714-G, rs10741657-A, rs1562902-C, and rs10766197-G alleles were significantly associated with increased susceptibility to HCV infection (all PFDR < 0.05, in additive/dominant models), and the combined effect of the four unfavorable alleles was related to an elevated risk of HCV infection in a locus-dosage manner (Ptrend = 0.008). Moreover, haplotype analysis suggested that, compared with the most frequent haplotype (Ars12794714Grs10741657Trs1562902Ars10766197), the haplotype containing four unfavorable alleles, GACG, was associated with a higher risk of HCV infection. The results of our study suggest that genetic variants in CYP2R1 may be biomarkers for predicting the susceptibility to HCV infection in the Chinese population.
Collapse
Affiliation(s)
- Jing-Jing Yang
- Hohai University Hospital, Hohai University, Nanjing, China
| | - Hao-Zhi Fan
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Ting Tian
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China
| | - Meng-Ping Wu
- Department of Information, The First People's Hospital of Lianyungang, Lianyungang, China
| | - Chao-Nan Xie
- Nanjing Qixia Health Inspection Institute, Nanjing, China
| | - Peng Huang
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Rong-Bin Yu
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Hong-Gang Yi
- Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Yun Zhang
- Institute of Epidemiology and Microbiology, Huadong Research Institute for Medicine and Biotechnics, Nanjing, China
| | - Jie Wang
- Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, China.
| |
Collapse
|
|
18
|
Thanapirom K, Suksawatamnuay S, Sukeepaisarnjaroen W, Tangkijvanich P, Thaimai P, Wasitthankasem R, Poovorawan Y, Komolmit P. Genetic associations of vitamin D receptor polymorphisms with advanced liver fibrosis and response to pegylated interferon-based therapy in chronic hepatitis C. PeerJ 2019; 7:e7666. [PMID: 31565578 PMCID: PMC6744935 DOI: 10.7717/peerj.7666] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Accepted: 08/13/2019] [Indexed: 12/25/2022] Open
Abstract
Vitamin D receptor (VDR) modulates host immune responses to infections such as hepatitis C virus (HCV) infection, including interferon signaling. This study aimed to investigate the associations of VDR polymorphisms with advanced liver fibrosis and response to pegylated interferon (PEG-IFN)-based therapy in patients with chronic HCV infection. In total, 554 Thai patients with chronic HCV infection treated with a PEG-IFN-based regimen were enrolled. Six single-nucleotide polymorphisms (SNPs) were genotyped: the IL28B C > T (rs12979860) SNP and five VDR SNPs, comprising FokI T > C (rs2228570), BsmI C > T (rs1544410), Tru9I G > A (rs757343), ApaI C > A (rs7975232), and TaqI A > G (rs731236). In total, 334 patients (60.3%) achieved sustained virological response (SVR), and 255 patients (46%) were infected with HCV genotype 1. The bAt (CCA) haplotype, consisting of the BsmI rs1544410 C, ApaI rs7975232 C, and TaqI rs731236 A alleles, was associated with poor response (in terms of lack of an SVR) to PEG-IFN-based therapy. The IL28B rs12979860 CT/TT genotypes (OR = 3.44, 95% CI [2.12–5.58], p < 0.001), bAt haplotype (OR = 2.02, 95% CI [1.04–3.91], p = 0.03), pre-treatment serum HCV RNA (logIU/mL; OR = 1.73, 95% CI [1.31–2.28], p < 0.001), advanced liver fibrosis (OR = 1.68, 95% CI [1.10–2.58], p = 0.02), and HCV genotype 1 (OR = 1.59, 95% CI [1.07–2.37], p = 0.02) independently predicted poor response. Patients with the bAt haplotype were more likely to have poor response compared to patients with other haplotypes (41.4% vs 21.9%, p = 0.03). The FokI rs2228570 TT/TC genotypes (OR = 1.63, 95% CI [1.06–2.51], p = 0.03) and age ≥55 years (OR = 2.25; 95% CI [1.54–3.32], p < 0.001) were independently associated with advanced liver fibrosis, assessed based on FIB-4 score >3.25. VDR polymorphisms were not associated with pre-treatment serum HCV RNA. In Thai patients with chronic HCV infection, the bAt haplotype is associated with poor response to PEG-IFN-based therapy, and the FokI rs2228570 TT/TC genotypes are risk factors for advanced liver fibrosis.
Collapse
Affiliation(s)
- Kessarin Thanapirom
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.,Chulalongkorn University, Liver Fibrosis and Cirrhosis Research Unit, Bangkok, Thailand
| | - Sirinporn Suksawatamnuay
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.,Chulalongkorn University, Liver Fibrosis and Cirrhosis Research Unit, Bangkok, Thailand
| | - Wattana Sukeepaisarnjaroen
- Department of Medicine, Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Gastroenterology unit, Khon Kaen, Thailand
| | - Pisit Tangkijvanich
- Faculty of Medicine, Chulalongkorn University, Department of Biochemistry, Bangkok, Thailand
| | - Panarat Thaimai
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.,Chulalongkorn University, Liver Fibrosis and Cirrhosis Research Unit, Bangkok, Thailand
| | - Rujipat Wasitthankasem
- Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Center of Excellence in Clinical Virology, Bangkok, Thailand
| | - Yong Poovorawan
- Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Center of Excellence in Clinical Virology, Bangkok, Thailand
| | - Piyawat Komolmit
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.,Chulalongkorn University, Liver Fibrosis and Cirrhosis Research Unit, Bangkok, Thailand
| |
Collapse
|
|
19
|
Gürbüz F, Ağın M, Mengen E, Elçi H, Ünal İ, Tümgör G, Yüksel B. Kronik karaciğer hastalığı olan çocukların D vitamini düzeyleri. CUKUROVA MEDICAL JOURNAL 2018. [DOI: 10.17826/cumj.365057] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
|
|
20
|
Udomsinprasert W, Jittikoon J. Vitamin D and liver fibrosis: Molecular mechanisms and clinical studies. Biomed Pharmacother 2018; 109:1351-1360. [PMID: 30551386 DOI: 10.1016/j.biopha.2018.10.140] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Revised: 10/22/2018] [Accepted: 10/24/2018] [Indexed: 12/21/2022] Open
Abstract
Vitamin D plays a primary role in regulation of bone metabolism and calcium homeostasis. Interestingly, emerging evidence suggests protective effects of vitamin D against liver fibrogenesis. However, the precise mechanisms of this action remain mysterious. Herein, this review aimed to summarize the role of vitamin D in liver fibrosis pathology and to update the current comprehensive knowledge regarding the clinical utility of vitamin D-based treatment in liver fibrosis. In regard to its effect on liver fibrosis, vitamin D possesses an anti-fibrotic effect on hepatic stellate cells via vitamin D receptor-mediated specific signal transduction pathways, which in turn inhibit expression of pro-fibrogenic genes. Furthermore, several studies demonstrated a significant association between low vitamin D levels and an increased risk of liver fibrosis. Additionally, high prevalence of vitamin D deficiency was noted in patients with liver fibrosis, suggesting the use of vitamin D status as a biochemical marker reflecting the progression of liver fibrosis. It is therefore reasonable to postulate that vitamin D supplementation being a cost effective and relative simple procedure may benefit to liver fibrosis. Nevertheless, further research is needed to fully elucidate its regulatory role in inhibiting liver fibrogenesis and to estimate the safety and efficiency of vitamin D supplementation as a relatively inexpensive treatment for liver fibrosis in patients with chronic liver diseases.
Collapse
Affiliation(s)
- Wanvisa Udomsinprasert
- Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.
| | - Jiraphun Jittikoon
- Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.
| |
Collapse
|
|
21
|
Mayr U, Fahrenkrog-Petersen L, Batres-Baires G, Rasch S, Herner A, Schmid RM, Huber W, Lahmer T. Vitamin D Deficiency Is Highly Prevalent in Critically Ill Patients and a Risk Factor for Mortality: A Prospective Observational Study Comparing Noncirrhotic Patients and Patients With Cirrhosis. J Intensive Care Med 2018; 35:992-1001. [PMID: 30270710 DOI: 10.1177/0885066618803844] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION A 25-hydroxyvitamin D, 25(OH)D, deficiency is common among critically ill patients and correlated with increased mortality. Furthermore, deficiency is associated with advanced liver disease. However, there are no studies available comparing the dimensions and consequences of a 25(OH)D deficiency between patients with and without liver cirrhosis in the setting of intensive care units (ICUs). This study focuses on differences in 25(OH)D status between critically ill noncirrhosis patients and patients with cirrhosis (primary end point), hypothesizing that deficiency and its impact on mortality risk are even more pronounced in patients with cirrhosis. METHODS We performed a prospective observational study of 176 patients (noncirrhosis patients, N = 114; patients with cirrhosis, N = 62) with a laboratory assessment of 25(OH)D on ICU admission and survival analyses after 180 days. RESULTS On admission, 55% of patients showed a severe deficiency, 25(OH)D <10 ng/mL, and a further 23% moderate deficiency (10-19 ng/mL). The overall median level of 25(OH)D was 8.0 (5.0-18.0) ng/mL (10.5 [6.0-21.3] in noncirrhosis patients vs 7.0 [4.8-10.0] in patients with cirrhosis; P < .001). We found extremely low levels particularly in patients without prior vitamin D supplementation (6.0 [4.0-7.5] in patients with cirrhosis vs 8.0 [5.0-12.0] ng/mL in noncirrhosis patients; P = .004). Vitamin D status correlated inversely with the sequential organ failure assessment, acute and physiology chronic health evaluation, model of end-stage liver disease, and Child-Pugh scores. Survival analyses categorized 25(OH)D levels <10 ng/mL as a high-risk factor for mortality 180 days after admission (hazard ratio [HR]: 2.45, 95% confidence interval [CI] = 1.60-3.70; P < .001). In patients with cirrhosis, a severe deficiency (<10 ng/mL) involved a significantly higher mortality risk than in noncirrhosis patients (HR: 2.30, 95% CI = 1.39-3.82; P = .001). In cases of admission levels ≥10 ng/mL, however, mortality risk was similar between patients with cirrhosis and noncirrhosis patients (HR: 1.08, 95% CI = 0.43-2.73; P = .873). CONCLUSIONS Hypovitaminosis D is a highly frequent disorder in critically ill patients admitted to ICU. A severe deficiency with levels <10 ng/mL is a high risk factor for increased mortality, especially in patients with cirrhosis.
Collapse
Affiliation(s)
- Ulrich Mayr
- 2nd Medical Department, Klinikum rechts der Isar, Technical University Munich, München, Germany
| | | | - Gonzalo Batres-Baires
- 2nd Medical Department, Klinikum rechts der Isar, Technical University Munich, München, Germany
| | - Sebastian Rasch
- 2nd Medical Department, Klinikum rechts der Isar, Technical University Munich, München, Germany
| | - Alexander Herner
- 2nd Medical Department, Klinikum rechts der Isar, Technical University Munich, München, Germany
| | - Roland M Schmid
- 2nd Medical Department, Klinikum rechts der Isar, Technical University Munich, München, Germany
| | - Wolfgang Huber
- 2nd Medical Department, Klinikum rechts der Isar, Technical University Munich, München, Germany
| | - Tobias Lahmer
- 2nd Medical Department, Klinikum rechts der Isar, Technical University Munich, München, Germany
| |
Collapse
|
|
22
|
Lai GY, Wang JB, Weinstein SJ, Parisi D, Horst RL, McGlynn KA, Männistö S, Albanes D, Freedman ND. Association of 25-Hydroxyvitamin D with Liver Cancer Incidence and Chronic Liver Disease Mortality in Finnish Male Smokers of the ATBC Study. Cancer Epidemiol Biomarkers Prev 2018; 27:1075-1082. [PMID: 29720370 PMCID: PMC6148352 DOI: 10.1158/1055-9965.epi-17-0877] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2017] [Revised: 12/19/2017] [Accepted: 04/27/2018] [Indexed: 01/23/2023] Open
Abstract
Background: Although circulating 25-hydroxyvitamin D [25(OH)D] concentrations were linked to liver cancer and chronic liver disease (CLD) in laboratory studies, few epidemiologic studies have addressed the associations.Methods: Within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, we measured 25(OH)D in baseline serum of 202 incident liver cancer cases and 225 CLD deaths that occurred during nearly 25 years of follow-up, and 427 controls. ORs and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. We examined predetermined clinically defined cut-points, and season-specific and season-standardized quartiles.Results: Low serum 25(OH)D concentrations were associated with higher risk of liver cancer (<25 nmol/L vs. ≥50 nmol/L: 1.98; 95% CI, 1.22-3.20; Ptrend across categories = 0.003) and CLD mortality (1.93; 95% CI, 1.23-3.03; Ptrend = 0.006) in models adjusted for age and date of blood draw. After additional adjustment for body mass index, diabetes, smoking, and other potential confounders, the association remained statistically significant for liver cancer (1.91; 95% CI, 1.16-3.15; Ptrend = 0.008), but was somewhat attenuated for CLD mortality (1.67; 95% CI, 1.02-2.75; Ptrend = 0.05). Associations were similar for analyses using season-specific and season-standardized quartiles, and after excluding participants with diabetes, or hepatitis B or C.Conclusions: Our results suggest a possible preventive role for vitamin D against liver cancer and CLD, although the importance of the liver for vitamin D metabolism and the lack of information about underlying liver disease makes reverse causality a concern.Impact: Future studies are needed to evaluate associations of vitamin D with liver cancer and liver disease in other populations, particularly those with a different constellation of risk factors. Cancer Epidemiol Biomarkers Prev; 27(9); 1075-82. ©2018 AACR.
Collapse
Affiliation(s)
- Gabriel Y Lai
- Environmental Epidemiology Branch, Epidemiology and Genomics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland.
| | - Jian-Bing Wang
- Department of Epidemiology and Health Statistics, School of Public Health, Zhejiang University, Hangzhou, China
| | - Stephanie J Weinstein
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland
| | | | | | - Katherine A McGlynn
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland
| | - Satu Männistö
- Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland
| | - Demetrius Albanes
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland
| | - Neal D Freedman
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland
| |
Collapse
|
|
23
|
Abstract
In the past few years, a growing body of clinical evidence has highlighted the risk of vitamin D deficiency in patients with chronic hepatitis C and that vitamin D levels are associated with the course of hepatitis C virus (HCV) infection, adverse effects, and treatment response to peginterferon/ribavirin. Recently, studies have found that vitamin D status is related to drug resistance and increased risk of infection in patients with liver cirrhosis. Vitamin D-related gene polymorphisms have been found to explain the interactions between vitamin D deficiency and HCV infection, offering a new perspective toward understanding the current problems such as the development of insulin resistance and racial differences in sustained virological response. Studies have been conducted to determine whether vitamin D supplementation as an adjuvant yields a better result compared with traditional HCV treatment. Here, we provide a brief review of the past and present knowledge of vitamin D in HCV infection.
Collapse
|
|
24
|
Azevedo LA, Matte U, Silveira TR, Bonfanti JW, Bruch JP, Álvares-da-Silva MR. Effect of Vitamin D Serum Levels and GC Gene Polymorphisms in Liver Fibrosis Due to Chronic Hepatitis C. Ann Hepatol 2018; 16:742-748. [PMID: 28809744 DOI: 10.5604/01.3001.0010.2748] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIM Vitamin D has been associated with chronic liver diseases and low vitamin levels may contribute to progression of chronic hepatitis C. The aim of this study was to evaluate the influence of vitamin D serum levels and GC gene polymorphisms in the severity of liver fibrosis in patients with chronic hepatitis C genotype 1. MATERIAL AND METHODS Cross-sectional study that enrolled 132 adult patients with chronic hepatitis C genotype 1 attended at the outpatient Clinic of Gastroenterology Division at Hospital de Clínicas de Porto Alegre. At the time of enrollment patients had a blood withdraw for serum 25(OH)D determination and genotypic analysis of rs7041 and rs4588 polymorphisms in GC gene. None/mild fibrosis was considered as METAVIR F0, F1 and F2 and severe fibrosis as METAVIR F3 and F4. RESULTS Median 25(OH)D levels in the sample were 19.9 ng/mL (P25-P75: 14.0-29.4). Fifty percent of patients presented vitamin D deficiency (< 20 ng/mL). In stepwise multiple linear regression the variables associated with 25(OH)D levels were blood withdrawn in Winter/spring season, the haplotypes AT/AT + AG/AT of rs7041 and rs4588 and female sex. For evaluation of severe fibrosis, variables associated in logistic regression were age, vitamin D severe deficiency (< 10 ng/mL), glucose levels, BMI and platelets count. CONCLUSIONS Vitamin D levels are associated with severity of liver fibrosis in chronic hepatitis C genotype 1 patients. Although the rs7041 and rs4588 GC polymorphisms are strong predictors of vitamin D levels, they do not play a direct role in liver fibrosis.
Collapse
Affiliation(s)
- Laura A Azevedo
- Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil Graduate Program in Gastroenterology and Hepatology Sciences
| | - Ursula Matte
- Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil Department of Genetics; Graduate Program in Genetics and Molecular Biology
| | - Themis R Silveira
- Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil Graduate Program in Gastroenterology and Hepatology Sciences
| | - Jacqueline W Bonfanti
- Universidade Federal do Rio Grande do Sul Division of Gastroenterology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil Department of Internal Medicine
| | - Juliana P Bruch
- Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil Graduate Program in Gastroenterology and Hepatology Sciences
| | - Mário R Álvares-da-Silva
- Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil Graduate Program in Gastroenterology and Hepatology Sciences
| |
Collapse
|
|
25
|
Moretti R, Caruso P, Tecchiolli M, Gazzin S, Tiribelli C. Management of restless legs syndrome in chronic liver disease: A challenge for the correct diagnosis and therapy. World J Hepatol 2018; 10:379-387. [PMID: 29599901 PMCID: PMC5871858 DOI: 10.4254/wjh.v10.i3.379] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2017] [Revised: 12/27/2017] [Accepted: 01/24/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the association between restless legs syndrome (RLS) and well-defined chronic liver disease, and the possible therapeutic options.
METHODS Two hundred and eleven patients with chronic liver disease, complaining of sleep disturbances, painful leg sensation and daily sleepiness, were included. Patients with persistent alcohol intake, recent worsening of clinical conditions, or hepatitis C virus were excluded. Diagnosis of RLS was suggested by the Johns Hopkins questionnaire and verified by fulfilling the diagnostic criteria by Allen. All patients were tested, both at baseline and during follow-up, with the Hamilton rating scale for depression, sleep quality assessment (PSQI), Epworth sleepiness scale (ESS), International Restless Legs Syndrome Study Group evaluation, and international RLS severity (IRLS) scoring system. Iron-free level, ferritin, folate, vitamin B12 and D-OH25 were detected. Neurological examinations and blood test occurred at the beginning of the therapy, after 2 wk, and at the 28th, 75th, 105th, 135th, 165th and 205th day. Regarding therapy, pramipexole or gabapentin were used.
RESULTS Patients were moderately depressed, with evident nocturnal sleep problems and concomitant daily sleepiness. Sleep problems and involuntary leg movements had been underestimated, and RLS syndrome had not been considered before the neurological visit. All (211/211) patients fulfilled the RLS diagnostic criteria. Twenty-two patients considered their symptoms as mild, according to IRSL, but 189 found them moderate to very severe. No correlation was found between ammonium level and ESS or PSQI. Augmentation was rather precocious in our patients (135th day), and more frequent (35%) than previous data (8.3%-9.1%). The dosage of dopamine agonists was found to be associated with augmentation and appears in range with the literature. Previous intake of alcohol and lower levels of vitamins have been related to the phenomenon in our study.
CONCLUSION RLS is a common disorder, requiring rapid diagnosis and treatment. Further research is therefore fundamental.
Collapse
Affiliation(s)
- Rita Moretti
- Neurology Clinic, Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste 34149, Italy
| | - Paola Caruso
- Neurology Clinic, Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste 34149, Italy
| | - Marzia Tecchiolli
- Neurology Clinic, Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste 34149, Italy
| | - Silvia Gazzin
- Italian Liver Foundation, Centro Studi Fegato, Trieste 34149, Italy
| | | |
Collapse
|
|
26
|
Wu DB, Wang ML, Chen EQ, Tang H. New insights into the role of vitamin D in hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol 2018; 12:287-294. [PMID: 29140126 DOI: 10.1080/17474124.2018.1406307] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
In addition to being crucial for host immune defense, vitamin D is involved in cell proliferation, apoptosis, differentiation, inflammation, invasion and metastasis, angiogenesis and micro-RNA modulation. To date, clinical studies have demonstrated that vitamin D deficiency is common not only in patients with chronic liver diseases but also in those with hepatocellular carcinoma (HCC). Experimental studies have also demonstrated that vitamin D and its receptors are related to the occurrence of HCC and the prognoses of patients with HCC. Areas covered: In this review, we discuss the potential anti-tumor role of vitamin D in HCC based on current findings from epidemiological studies, basic science, and clinical studies and provide new insights into the pathogenesis and treatment of HCC. Expert commentary: Recent studies have revealed the anti-tumor effects of vitamin D to a certain degree. Vitamin D and its analogs may provide new treatment targets and prognostic factors for HCC that might be essential for the primary or secondary prevention of HCC and the monitoring of its progression.
Collapse
Affiliation(s)
- Dong-Bo Wu
- a Center of Infectious Diseases , West China Hospital of Sichuan University , Chengdu , China
| | - Meng-Lan Wang
- a Center of Infectious Diseases , West China Hospital of Sichuan University , Chengdu , China
| | - En-Qiang Chen
- a Center of Infectious Diseases , West China Hospital of Sichuan University , Chengdu , China
| | - Hong Tang
- a Center of Infectious Diseases , West China Hospital of Sichuan University , Chengdu , China
| |
Collapse
|
|
27
|
Gayam V, Mandal AK, Khalid M, Mukhtar O, Gill A, Garlapati P, Tiongson B, Sherigar J, Mansour M, Mohanty S. Association Between Vitamin D Levels and Treatment Response to Direct-Acting Antivirals in Chronic Hepatitis C: A Real-World Study. Gastroenterology Res 2018; 11:309-316. [PMID: 30116431 PMCID: PMC6089592 DOI: 10.14740/gr1072w] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2018] [Accepted: 07/23/2018] [Indexed: 12/11/2022] Open
Abstract
Background Low serum vitamin D levels in chronic hepatitis C (CHC) is associated with advanced liver fibrosis; and there remains an imprecise relationship with the treatment response based on the vitamin D levels. Previous studies have shown conflicting results on the vitamin D levels, and association with treatment response in CHC treated with interferon-based regimens. Methods Patients with CHC treated with direct-acting antivirals (DAAs) between January 2016 and December 2017 in the community clinic setting were retrospectively analyzed. Pretreatment baseline patient characteristics, treatment efficacy with the sustained virologic response at 12 weeks post-treatment (SVR 12) were assessed in CHC patients with deficient, insufficient, and normal levels of vitamin D measured before the initiation of DAA therapy. Results Two hundred and ninety-one patients were included in the study. Direct-acting antivirals included in the study were ledipasvir/sofosbuvir ± ribavirin, ombitasvir + paritaprevir + ritonavir + dasabuvir ± ribavirin, and sofosbuvir/velpatasvir. An overall sustained virologic response was achieved in 95% (n = 276) of patients. SVR 12 rates among patients with vitamin D deficiency, vitamin D insufficiency and normal vitamin D levels were 92%, 96.2%, and 97.2% respectively and was not statically significant (P = 0.214). A total of 71 patients were cirrhotic. The prevalence of vitamin D insufficiency (20 - 29.9 ng/mL) and deficiency (< 20 ng/mL) was significantly higher in cirrhotic patients (P = 0.01). Despite this, pretreatment vitamin D levels did not show any impact on the virologic response. The most common adverse effect observed was fatigue. None of the patients had to discontinue the treatment due to adverse events. Conclusions DAAs are safe and effective with a high overall SVR 12 in CHC and treatment response does not depend on the pretreatment vitamin D levels. The prevalence of both vitamin D insufficiency and deficiency was observed to be higher in cirrhotic cohorts compared to non-cirrhotic counterparts.
Collapse
Affiliation(s)
- Vijay Gayam
- Department of Medicine and Gastroenterology, Interfaith Medical Center, 1545 Atlantic Avenue. Brooklyn, NY 11213, USA
| | - Amrendra Kumar Mandal
- Department of Medicine and Gastroenterology, Interfaith Medical Center, 1545 Atlantic Avenue. Brooklyn, NY 11213, USA
| | - Mazin Khalid
- Department of Medicine and Gastroenterology, Interfaith Medical Center, 1545 Atlantic Avenue. Brooklyn, NY 11213, USA
| | - Osama Mukhtar
- Department of Medicine and Gastroenterology, Interfaith Medical Center, 1545 Atlantic Avenue. Brooklyn, NY 11213, USA
| | - Arshpal Gill
- Department of Medicine and Gastroenterology, Interfaith Medical Center, 1545 Atlantic Avenue. Brooklyn, NY 11213, USA
| | - Pavani Garlapati
- Department of Medicine and Gastroenterology, Interfaith Medical Center, 1545 Atlantic Avenue. Brooklyn, NY 11213, USA
| | - Benjamin Tiongson
- Department of Medicine and Gastroenterology, Interfaith Medical Center, 1545 Atlantic Avenue. Brooklyn, NY 11213, USA
| | - Jagannath Sherigar
- Department of Medicine and Division of Gastroenterology and Hepatology, New York-Presbyterian Brooklyn Methodist Hospital, 506, 6th St, Brooklyn, NY 11215, USA
| | - Mohammed Mansour
- Department of Medicine and Gastroenterology, Interfaith Medical Center, 1545 Atlantic Avenue. Brooklyn, NY 11213, USA
| | - Smruti Mohanty
- Department of Medicine and Division of Gastroenterology and Hepatology, New York-Presbyterian Brooklyn Methodist Hospital, 506, 6th St, Brooklyn, NY 11215, USA
| |
Collapse
|
|
28
|
Yu R, Tan D, Ning Q, Niu J, Bai X, Chen S, Cheng J, Yu Y, Wang H, Xu M, Shi G, Wan M, Chen X, Tang H, Sheng J, Dou X, Shi J, Ren H, Wang M, Zhang H, Gao Z, Chen C, Ma H, Jia J, Hou J, Xie Q, Sun J. Association of baseline vitamin D level with genetic determinants and virologic response in patients with chronic hepatitis B. Hepatol Res 2018; 48:E213-E221. [PMID: 28834607 DOI: 10.1111/hepr.12972] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2017] [Revised: 07/17/2017] [Accepted: 08/18/2017] [Indexed: 02/05/2023]
Abstract
AIM The role of vitamin D in individuals with chronic hepatitis B (CHB) is unclear. We aimed to explore the association of baseline vitamin D level with genetic determinants and week-104 treatment outcome in CHB patients. METHODS Baseline serum 25-hydroxycholecalciferol (25(OH)D) levels and genetic polymorphism within GC, DHCR7, and CYP2R1 were determined in stored serum of 560 patients who were enrolled into a multicenter, randomized, controlled study and completed 104 weeks of telbivudine monotherapy or telbivudine-based optimized therapy. Virologic response was defined as hepatitis B virus DNA <300 copies/mL (52 IU/mL) at week 104. RESULTS The mean 25(OH)D value was 29.64 ng/mL. The percentage of patients with vitamin D insufficiency (<30 ng/mL) and vitamin D deficiency (<20 ng/mL) were 55.0% and 20.9%, respectively. Gender, season, latitude, and GC rs2282679 polymorphism were independent factors of vitamin D status. Patients with sufficient vitamin D (≥30 ng/mL) achieved a higher virologic response rate than those with vitamin D insufficiency (81.7% vs. 67.2%, P < 0.001). The area under the curve of 25(OH)D to predict virologic response was 0.65 (P < 0.001; 95% confidence interval, 0.62-0.67). On multivariate analysis, 25(OH)D level was an independent predictor of virologic response, but not associated with hepatitis B envelope antigen (HBeAg) seroconversion or alanine aminotransferase (ALT) normalization. CONCLUSIONS Vitamin D insufficiency was highly prevalent in treatment-naïve CHB patients in mainland China. Latitude and genetic determinants affect vitamin D status. Baseline vitamin D level can predict week-104 virologic response, but not HBeAg seroconversion or ALT normalization.
Collapse
Affiliation(s)
- Rui Yu
- Department of Infectious Diseases, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China.,Department of Digestive Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Deming Tan
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, China
| | - Qin Ning
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Junqi Niu
- Hepatology Unit, No. 1 Hospital affiliated to Jilin University, Changchun, China
| | - Xuefan Bai
- Department of Infectious Diseases, Tangdu Hospital, Xi'an, China
| | - Shijun Chen
- Ji'nan Infectious Diseases Hospital, Ji'nan, China
| | - Jun Cheng
- Beijing Ditan Hospital, Beijing, China
| | - Yanyan Yu
- Department of Infectious Diseases, First Hospital of Peking University, Beijing, China
| | - Hao Wang
- Hepatology Unit, Peking University People's Hospital, Beijing, China
| | - Min Xu
- 8th People's Hospital, Guangzhou, China
| | - Guangfeng Shi
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Mobin Wan
- Department of Infectious Diseases, Changhai Hospital, Shanghai, China
| | | | - Hong Tang
- Department of Infectious Diseases, West China Hospital, Chengdu, China
| | - Jifang Sheng
- Department of Infectious Diseases, Zhejiang University 1st Affiliated Hospital, Hangzhou, China
| | - Xiaoguang Dou
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, China
| | | | - Hong Ren
- Department of Infectious Diseases, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Maorong Wang
- Department of Infectious Diseases, 81st PLA Hospital, Nanjing, China
| | | | - Zhiliang Gao
- Department of Infectious Diseases, Sun Yat-Sen University 3rd Affiliated Hospital, Guangzhou, China
| | - Chengwei Chen
- Department of Infectious Diseases, 85th PLA Hospital, Shanghai, China
| | - Hong Ma
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Jinlin Hou
- Department of Infectious Diseases, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jian Sun
- Department of Infectious Diseases, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| |
Collapse
|
|
29
|
Hoan NX, Tong HV, Song LH, Meyer CG, Velavan TP. Vitamin D deficiency and hepatitis viruses-associated liver diseases: A literature review. World J Gastroenterol 2018; 24:445-460. [PMID: 29398866 PMCID: PMC5787780 DOI: 10.3748/wjg.v24.i4.445] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Revised: 01/08/2018] [Accepted: 01/16/2018] [Indexed: 02/06/2023] Open
Abstract
The secosteroid hormone vitamin D has, in addition to its effects in bone metabolism also functions in the modulation of immune responses against infectious agents and in inhibiting tumorigenesis. Thus, deficiency of vitamin D is associated with several malignancies, but also with a plethora of infectious diseases. Among other communicable diseases, vitamin D deficiency is involved in the pathogenesis of chronic liver diseases caused by hepatitis B and C viruses (HBV, HCV) and high prevalence of vitamin D deficiency with serum levels below 20 mg/mL in patients with HBV and HCV infection are found worldwide. Several studies have assessed the effects of vitamin D supplementation on the sustained virological response (SVR) to interferon (IFN) plus ribavirin (RBV) therapy in HBV and HCV infection. In these studies, inconsistent results were reported. This review addresses general aspects of vitamin D deficiency and, in particular, the significance of vitamin D hypovitaminosis in the outcome of HBV- and HCV-related chronic liver diseases. Furthermore, current literature was reviewed in order to understand the effects of vitamin D supplementation in combination with IFN-based therapy on the virological response in HBV and HCV infected patients.
Collapse
Affiliation(s)
- Nghiem Xuan Hoan
- Institute of Clinical Infectious Diseases, 108 Military Central Hospital, Hanoi 10004, Vietnam
- Molecular Genetics of Infectious Diseases, Institute of Tropical Medicine, University of Tübingen, Tübingen 72074, Germany
- Vietnamese-German Center of Medical Research (VG-CARE), Hanoi 10004, Vietnam
| | - Hoang Van Tong
- Vietnamese-German Center of Medical Research (VG-CARE), Hanoi 10004, Vietnam
- Institute of Biomedicine and Pharmacy, Vietnam Military Medical University, Hanoi 10004, Vietnam
| | - Le Huu Song
- Institute of Clinical Infectious Diseases, 108 Military Central Hospital, Hanoi 10004, Vietnam
- Vietnamese-German Center of Medical Research (VG-CARE), Hanoi 10004, Vietnam
| | - Christian G Meyer
- Molecular Genetics of Infectious Diseases, Institute of Tropical Medicine, University of Tübingen, Tübingen 72074, Germany
- Vietnamese-German Center of Medical Research (VG-CARE), Hanoi 10004, Vietnam
- Medical Faculty, Duy Tan University, Da Nang, Vietnam
| | - Thirumalaisamy P Velavan
- Molecular Genetics of Infectious Diseases, Institute of Tropical Medicine, University of Tübingen, Tübingen 72074, Germany
- Vietnamese-German Center of Medical Research (VG-CARE), Hanoi 10004, Vietnam
- Medical Faculty, Duy Tan University, Da Nang, Vietnam
| |
Collapse
|
|
30
|
Bae M, Park YK, Lee JY. Food components with antifibrotic activity and implications in prevention of liver disease. J Nutr Biochem 2017; 55:1-11. [PMID: 29268106 DOI: 10.1016/j.jnutbio.2017.11.003] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2017] [Revised: 09/18/2017] [Accepted: 11/11/2017] [Indexed: 12/26/2022]
Abstract
Increasing prevalence of nonalcoholic fatty liver disease (NAFLD) in parallel with the obesity epidemic has been a major public health concern. NAFLD is the most common chronic liver disease in the United States, ranging from fatty liver to steatohepatitis, fibrosis and cirrhosis in the liver. In response to chronic liver injury, fibrogenesis in the liver occurs as a protective response; however, prolonged and dysregulated fibrogenesis can lead to liver fibrosis, which can further progress to cirrhosis and eventually hepatocellular carcinoma. Interplay of hepatocytes, macrophages and hepatic stellate cells (HSCs) in the hepatic inflammatory and oxidative milieu is critical for the development of NAFLD. In particular, HSCs play a major role in the production of extracellular matrix proteins. Studies have demonstrated that bioactive food components and natural products, including astaxanthin, curcumin, blueberry, silymarin, coffee, vitamin C, vitamin E, vitamin D, resveratrol, quercetin and epigallocatechin-3-gallate, have antifibrotic effects in the liver. This review summarizes current knowledge of the mechanistic insight into the antifibrotic actions of the aforementioned bioactive food components.
Collapse
Affiliation(s)
- Minkyung Bae
- Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA
| | - Young-Ki Park
- Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA
| | - Ji-Young Lee
- Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA; Department of Food and Nutrition, Kyung Hee University, Seoul, South Korea.
| |
Collapse
|
|
31
|
Komolmit P, Kimtrakool S, Suksawatamnuay S, Thanapirom K, Chattrasophon K, Thaimai P, Chirathaworn C, Poovorawan Y. Vitamin D supplementation improves serum markers associated with hepatic fibrogenesis in chronic hepatitis C patients: A randomized, double-blind, placebo-controlled study. Sci Rep 2017; 7:8905. [PMID: 28827788 PMCID: PMC5566364 DOI: 10.1038/s41598-017-09512-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2017] [Accepted: 07/26/2017] [Indexed: 12/14/2022] Open
Abstract
Hepatic fibrosis is the net accumulation of matrix tissue components which controlled by pro-fibrolytic enzymes, matrix metalloproteinases (MMPs), and pro-fibrotic cytokine, TGF-β1, and enzymes, tissue inhibitors of MMPs (TIMPs). Vitamin D (VD) supplementation has been shown to reverse these processes in vitro and in vivo. This study sought to determine the effect of VD supplementation on serum fibrotic markers in chronic hepatitis C (CHC) patients. Fifty-four CHC patients with VD deficiency were randomized into two groups, a VD group (n = 29) and a placebo group (n = 29). The serum levels of 25-hydroxy VD, TGF-β1, TIMP-1, MMP2 and MMP9 were measured at baseline and at the end of the 6-week study period. Upon correction of VD levels, TGF-β1 and TIMP-1 levels were decreased, and the MMP2 and MMP9 levels were significantly increased in the VD group. A comparison of the mean changes (delta) in the markers between groups showed that TGF-β1 and TIMP-1 levels were significantly decreased and the MMP2 and MMP9 were significantly higher in the VD group than in the placebo group. By using CHC patients as a model, this study provides additional evidence that VD plays an important role in the reversal of hepatic fibrogenesis.
Collapse
Affiliation(s)
- Piyawat Komolmit
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. .,Center of Excellence in Liver Diseases: King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
| | - Sayamon Kimtrakool
- Gastroenterology Unit, Department of Medicine, Lerdsin Hospital, Bangkok, Thailand
| | - Sirinporn Suksawatamnuay
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.,Center of Excellence in Liver Diseases: King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Kessarin Thanapirom
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.,Center of Excellence in Liver Diseases: King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Kanita Chattrasophon
- Gastroenterology Unit, Department of Medicine, Taksin Hospital, Bangkok, Thailand
| | - Panarat Thaimai
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Chintana Chirathaworn
- Division of Immunology, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Yong Poovorawan
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| |
Collapse
|
|
32
|
Ko BJ, Kim YS, Kim SG, Park JH, Lee SH, Jeong SW, Jang JY, Kim HS, Kim BS, Kim SM, Kim YD, Cheon GJ, Lee BR. Relationship between 25-Hydroxyvitamin D Levels and Liver Fibrosis as Assessed by Transient Elastography in Patients with Chronic Liver Disease. Gut Liver 2017; 10:818-25. [PMID: 27114415 PMCID: PMC5003207 DOI: 10.5009/gnl15331] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2015] [Revised: 09/28/2015] [Accepted: 12/01/2015] [Indexed: 12/11/2022] Open
Abstract
Background/Aims Deficiencies of 25-hydroxyvitamin D (25(OH)D) are prevalent in patients with chronic liver disease (CLD). Liver fibrosis is the main determinant of CLD prognosis. The present study was performed to evaluate the correlation between 25(OH)D levels and liver fibrosis as assessed by transient elastography (TE) in patients with compensated CLD. Methods Serum 25(OH)D levels and liver stiffness were determined in a total of 207 patients who were subjected to the following exclusion criteria: patients with decompensated CLD; patients who had malignancies; patients who were taking medications; and patients who were pregnant. Results The most common etiology was chronic hepatitis B (53.1%). Advanced liver fibrosis (defined by TE [≥9.5 kPa]) was present in 75 patients (36.2%). There was a significant correlation between 25(OH)D deficiency and liver stiffness. Based on the multivariate analysis, the following factors were independently associated with advanced liver fibrosis: 25(OH)D deficiency (odds ratio [OR], 3.46; p=0.004), diabetes mellitus (OR, 3.04; p=0.041), and fibrosis-4 index (OR, 2.01; p<0.001). Conclusions Patients with compensated CLD exhibit a close correlation between vitamin D level and liver stiffness as assessed by TE. Vitamin D deficiency was independently associated with advanced liver fibrosis.
Collapse
Affiliation(s)
- Bong Jin Ko
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea
| | - Young Seok Kim
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea
| | - Sang Gyune Kim
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea
| | - Jung Hwan Park
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea
| | - Sae Hwan Lee
- Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea
| | - Soung Won Jeong
- Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Jae Young Jang
- Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Hong Soo Kim
- Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea
| | - Boo Sung Kim
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea
| | - Sun Mi Kim
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea
| | - Young Don Kim
- Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea
| | - Gab Jin Cheon
- Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea
| | - Bo Ra Lee
- Department of Biostatistical Consulting, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| |
Collapse
|
|
33
|
Genetic variants underlying vitamin D metabolism and VDR-TGFβ-1-SMAD3 interaction may impact on HCV progression: a study based on dbGaP data from the HALT-C study. J Hum Genet 2017; 62:969-977. [PMID: 28703134 DOI: 10.1038/jhg.2017.75] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2017] [Revised: 06/17/2017] [Accepted: 06/19/2017] [Indexed: 02/06/2023]
Abstract
Vitamin D deficiency is prevalent in liver disease and vitamin D has been shown to decrease hepatic fibrosis through an anti-TGFβ-1/SMAD3 effect mediated by the vitamin D receptor. Thus, we hypothesized that genetic variants involved in vitamin D metabolism and/or VDR/TGFβ-1/SMAD3 interaction could impact on the progression of chronic HCV. We obtained or imputed genotypes for 40 single nucleotide polymorphisms (SNPs) located in genes implicated in vitamin D metabolism from the HALT-C cohort via dbGaP. The HALT-C study followed 692 chronic HCV patients over 4 years, evaluating clinical outcomes including worsening of fibrosis, hepatic decompensation (gastric/esophageal bleeding, CTP>7, ascites, spontaneous bacterial peritonitis and encephalopathy), development of hepatocellular carcinoma, and liver death. We tested the selected SNPs for association with these outcomes in 681 HALT-C subjects. Eleven SNPs presented tendency towards significance (P<0.05): four SNPs in DHCR7 related to with hepatic decompensation (rs4944957, rs12800438, rs3829251 and rs4945008); two in GC to worsening of fibrosis and liver death (rs7041 and rs222020); two in CYP2R1 to ascites and hepatocellular carcinoma (rs7116978 and rs1562902); two in VDR to gastric/esophageal bleeding and hepatocellular carcinoma (rs4516035 and rs2239186); and one in SMAD3 to worsening of fibrosis and encephalopathy (rs2118610). Only rs1800469 in TGFB1 was statistically associated with hepatic decompensation after Bonferroni's correction (P<0.00125). In conclusion, rs1800469 in TGFB1 was associated to hepatic decompensation in chronic hepatitis C, while the other 11 described polymorphisms must be evaluated in a larger cohort to determine the possible role of vitamin D in hepatitis C.
Collapse
|
|
34
|
Okubo T, Atsukawa M, Tsubota A, Shimada N, Abe H, Yoshizawa K, Arai T, Nakagawa A, Itokawa N, Kondo C, Aizawa Y, Iwakiri K. Association between vitamin D deficiency and pre-existing resistance-associated hepatitis C virus NS5A variants. Hepatol Res 2017; 47:641-649. [PMID: 27487797 DOI: 10.1111/hepr.12784] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2016] [Revised: 06/21/2016] [Accepted: 07/27/2016] [Indexed: 12/15/2022]
Abstract
AIM Although interferon-free therapy with direct-acting antivirals has developed as a standard of care for chronic hepatitis C, the existence of resistance-associated variants (RAVs) has a negative impact on treatment results. Recently, several studies indicated a relationship between chronic hepatitis C and serum vitamin D levels. However, the relationship between RAVs at the hepatitis C virus non-structure 5A (NS5A) region and serum vitamin D level has not yet been examined. METHODS Among patients with genotype 1 chronic hepatitis C who were enrolled in a multicenter cooperative study, our subjects comprised 247 patients in whom it was possible to measure RAVs at the NS5A region. These RAVs were measured using a direct sequencing method. RESULTS The median age of patients was 70 years (range, 24-87 years), and the number of female patients was 135 (54.7%). The median serum 25(OH) D3 level was 22 ng/mL (range, 6-64 ng/mL). L31 and Y93 RAVs at the NS5A region were detected in 3.7% (9/247) and 13.4% (33/247) of patients, respectively. Multivariate analysis identified vitamin D deficiency (serum 25(OH) D3 ≤ 20 ng/mL) (P = 5.91 × 10⁻5 , odds ratio = 5.015) and elderly age (>70 years) (P = 1.85 × 10-3 , odds ratio = 3.364) as contributing independent factors associated with the presence of the L31 and/or Y93 RAVs. The Y93H RAV was detected in 25.9% (29/112) of patients with a vitamin D deficiency, and in 8.9% (12/135) of those with a serum 25(OH) D3 level >20 ng/mL (P = 4.90 × 10-3 ). CONCLUSION We showed that RAVs at the NS5A region are associated with vitamin D deficiency and elderly age, which may have a negative influence on innate/adaptive immune responses to hepatitis C virus infection.
Collapse
Affiliation(s)
- Tomomi Okubo
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan
| | - Masanori Atsukawa
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan
| | - Akihito Tsubota
- Core Research Facilities for Basic Science, Research Center for Medical Sciences, Jikei University School of Medicine, Tokyo, Japan
| | - Noritomo Shimada
- Division of Gastroenterology and Hepatology, Otakanomori Hospital, Chiba, Japan
| | - Hiroshi Abe
- Division of Gastroenterology and Hepatology, Jikei University School of Medicine Katsusika Medical Center, Tokyo, Japan
| | - Kai Yoshizawa
- Division of Gastroenterology, Machida Municipal Hospital, Tokyo, Japan
| | - Taeang Arai
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan
| | - Ai Nakagawa
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan
| | - Norio Itokawa
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan
| | - Chisa Kondo
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan
| | - Yoshio Aizawa
- Division of Gastroenterology and Hepatology, Jikei University School of Medicine Katsusika Medical Center, Tokyo, Japan
| | - Katsuhiko Iwakiri
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| |
Collapse
|
|
35
|
Thanapirom K, Suksawatamnuay S, Sukeepaisarnjaroen W, Tangkijvanich P, Treeprasertsuk S, Thaimai P, Wasitthankasem R, Poovorawan Y, Komolmit P. Vitamin D-related gene polymorphism predict treatment response to pegylated interferon-based therapy in Thai chronic hepatitis C patients. BMC Gastroenterol 2017; 17:54. [PMID: 28415985 PMCID: PMC5392932 DOI: 10.1186/s12876-017-0613-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2016] [Accepted: 04/11/2017] [Indexed: 12/16/2022] Open
Abstract
Background Patients with chronic hepatitis C (HCV) infection have high prevalence of vitamin D deficiency. Genome-wide association study data has showed that several genetic variants within vitamin D cascade affect vitamin D function. This study aimed to determine whether genetic polymorphisms of genes in the vitamin D pathway are associated with treatment responses to pegylated interferon (PEG-IFN)-based therapy in patients with chronic HCV infection. Methods The study included 623 Thai patients from 2 university hospitals diagnosed with chronic HCV infection who were treated with a PEG-IFN and ribavirin. Patients were genotyped for functional variants on vitamin D synthetic pathway including GC (rs4588, rs7041, rs22020, rs2282679), CYP2R1 (rs2060793, rs12794714), CYP27B1 (rs10877012), and DHCR7 (rs12785878). Pre-treatment predictors of sustained virologic response (SVR) at 24 weeks following discontinuation of therapy were identified using a logistic regression analysis. Results SVR was achieved by 60.5% of patients (52.9% with HCV genotype 1; 66.7% with HCV non-genotype 1). In 44.6% of HCV genotype 1-infected patients, only the variant rs12785878 in the DHCR7 locus was significantly associated with an SVR. HCV genotype 1 patients who had DHCR7 rs12785878 GT/TT had a higher rate of SVR than those with the GG allele (59.7% vs. 43.4%, P = 0.03), but in HCV non-genotype 1-infected patients, the SVR rate did not differ between the two groups (63.3% and 59.1% for GT/TT and GG allele, P = 0.54). By multivariate analysis, liver fibrosis stage 0–1 (OR = 5.00; 95% CI, 2.02–12.37; P < 0.001), and DHCR7 rs12785878 GT/TT allele (OR = 2.69; 95% CI, 1.03–7.05; P = 0.04) were independent pre-treatment predictors of SVR following PEG-IFN-based therapy in HCV genotype 1 patients. Baseline HCV RNA < 400,000 IU/ml (OR = 1.96; 95% CI, 1.13–3.39; P = 0.02) was the only independent predictor of SVR in HCV non-genotype 1 patients. The polymorphisms of GC, CYP2R1 and CYP27B1 were not associated with treatment outcome even in genotype 1 or non-genotype 1 HCV infection. Conclusion The DHCR7 polymorphism may be a pre-treatment predictive marker for response to PEG-IFN-based therapy in chronic HCV genotype 1 infection. Electronic supplementary material The online version of this article (doi:10.1186/s12876-017-0613-x) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Kessarin Thanapirom
- Divisions of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, No. 1873 Rama IV road, Pathumwan District, Bangkok, 10330, Thailand.,Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, No. 1873 Rama IV road, Bangkok, 10330, Thailand
| | - Sirinporn Suksawatamnuay
- Divisions of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, No. 1873 Rama IV road, Pathumwan District, Bangkok, 10330, Thailand.,Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, No. 1873 Rama IV road, Bangkok, 10330, Thailand
| | - Wattana Sukeepaisarnjaroen
- Gastroenterology unit, Department of Medicine, Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, No. 123 Mittraparp Highway, Muang District, Khon Kaen, 40002, Thailand
| | - Pisit Tangkijvanich
- Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, No. 1873 Rama IV road, Bangkok, 10330, Thailand
| | - Sombat Treeprasertsuk
- Divisions of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, No. 1873 Rama IV road, Pathumwan District, Bangkok, 10330, Thailand.,Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, No. 1873 Rama IV road, Bangkok, 10330, Thailand
| | - Panarat Thaimai
- Divisions of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, No. 1873 Rama IV road, Pathumwan District, Bangkok, 10330, Thailand.,Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, No. 1873 Rama IV road, Bangkok, 10330, Thailand
| | - Rujipat Wasitthankasem
- Center of Excellence in Clinical Virology Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, No. 1873 Rama IV road, Bangkok, 10330, Thailand
| | - Yong Poovorawan
- Center of Excellence in Clinical Virology Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, No. 1873 Rama IV road, Bangkok, 10330, Thailand
| | - Piyawat Komolmit
- Divisions of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, No. 1873 Rama IV road, Pathumwan District, Bangkok, 10330, Thailand. .,Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, No. 1873 Rama IV road, Bangkok, 10330, Thailand.
| |
Collapse
|
|
36
|
Komolmit P, Charoensuk K, Thanapirom K, Suksawatamnuay S, Thaimai P, Chirathaworn C, Poovorawan Y. Correction of vitamin D deficiency facilitated suppression of IP-10 and DPP IV levels in patients with chronic hepatitis C: A randomised double-blinded, placebo-control trial. PLoS One 2017; 12:e0174608. [PMID: 28376103 PMCID: PMC5380326 DOI: 10.1371/journal.pone.0174608] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2016] [Accepted: 03/12/2017] [Indexed: 12/31/2022] Open
Abstract
Vitamin D deficiency was common among patients with chronic hepatitis C (CHC) and had negative influence on treatment outcome. Correction of vitamin D deficiency improved treatment response. Interferon gamma-induced protein 10 (IP-10) and enzyme dipeptidyl peptidase-4 (DPP IV) involved in inflammatory responses in CHC. Their higher levels at pretreatment of CHC could predict poorer responses. Vitamin D suppressed expression of IP-10 from monocytes in vitro. In CHC patients, DPP IV involved in IP-10 regulation. We hypothesized that correction of vitamin D insufficiency or deficiency in CHC patients might restore immune dysregulation through a pathway linked to the TH1/Th2 cytokines, IP-10 or DPP IV. We conducted a double-blind, placebo-controlled trial. 80 CHC patients with vitamin D levels less than 30 ng/mL were assigned to receive vitamin D (40) or placebo (40) supplements for 6 weeks. The levels of 25-hydroxyvitamin D [25(OH)D], Th1/Th2 cytokines, IP-10 and DPP IV were measured at baseline and at the 6th week. At the end of study, the mean 25(OH)D level in vitamin D group was significantly increased and normalised. There were no changes in the level of Th1/Th2 cytokines. Our important finding revealed that upon correction of vitamin D insufficiency or deficiency, the serum IP-10 and DPP IV levels were decreased significantly as compare to the placebo group (delta changes; 83.27 vs -133.80; 95% CI [-326.910, -40.758], p = 0.0125, and 271.04 vs -518.69; 95% CI [-1179,15, -59.781], p = 0.0305, respectively. As previous evidences suggested that each factor individually influenced and predicted outcome of CHC treatment. Our results offer a new insight and help to piece the puzzle of vitamin D deficiency, IP-10 and DPP IV together in CHC. TRIAL REGISTRATION Thai Clinical Trials Registry TCTR20160429001.
Collapse
Affiliation(s)
- Piyawat Komolmit
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and Center of Excellence in Liver Diseases: King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Kriangsak Charoensuk
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and Center of Excellence in Liver Diseases: King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
- Division of Gastroenterology, Department of Internal medicine, Buddhachinaraj Hospital School of Medicine, Phitsanulok, Thailand
| | - Kessarin Thanapirom
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and Center of Excellence in Liver Diseases: King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Sirinporn Suksawatamnuay
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and Center of Excellence in Liver Diseases: King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Panarat Thaimai
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and Center of Excellence in Liver Diseases: King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Chintana Chirathaworn
- Division of Immunology, Department of Microbiology, Chulalongkorn university, Bangkok, Thailand
| | - Yong Poovorawan
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| |
Collapse
|
|
37
|
Hernández-Alvarez N, Pascasio Acevedo JM, Quintero E, Fernández Vázquez I, García-Eliz M, de la Revilla Negro J, Crespo García J, Hernández-Guerra M. Effect of season and sunlight on viral kinetics during hepatitis C virus therapy. BMJ Open Gastroenterol 2017; 4:e000115. [PMID: 28321328 PMCID: PMC5353279 DOI: 10.1136/bmjgast-2016-000115] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2016] [Revised: 10/28/2016] [Accepted: 11/28/2016] [Indexed: 02/07/2023] Open
Abstract
Background and aims Rapid viral response (RVR) during antiviral treatment for hepatitis C virus (HCV) predicts sustained viral response (SVR). Recently, vitamin D levels have been associated with SVR. As sunlight is the most important source of vitamin D and shows seasonal variation, we evaluated the effect of season on viral kinetics during peginterferon/ribavirin-based therapy for HCV. Methods Consecutive HCV patients treated with peginterferon/ribavirin and boceprevir/ telaprevir (June 2011–July 2014) were included. Patients were grouped according to season when therapy was initiated (Season A: May–October and Season B: November–April) depending on hours of daily sunlight. Multiple logistic regression analysis included factors known to influence SVR to treatment. The dependent variables were undetectable viral load (VL) or VL ≤15 UI/mL (VL ≤15) at weeks 4, 8 and 12, end of treatment and SVR. Results The study included 930 patients (66.8% men; median 54 years) treated with telaprevir (n=537) or boceprevir, without (n=481) or with lead-in therapy of peginterferon/ribavirin. Baseline characteristics of patients in Season A (45.3%, n=421) and Season B groups were similar. Overall, a higher rate of RVR (23.5% vs 16.1%, p=0.005) and VL ≤15 (51.0% vs 38.6%, p≤0.001) was observed in patients starting treatment during Season A versus Season B. By logistic regression analysis, initiating treatment in Season A proved to be an independent predictor of RVR and VL ≤15. Conclusions In our setting, seasonality affects viral kinetics in HCV genotype 1 patients treated with peginterferon/ribavirin-based therapy. Our findings support the hypothesis that vitamin D influences viral response to peginterferon/ribavirin-based therapy.
Collapse
Affiliation(s)
| | | | | | | | - María García-Eliz
- Hospital Universitari i Politècnic La Fe, CIBERehd , Valencia , Spain
| | | | | | | |
Collapse
|
|
38
|
Dadabhai AS, Saberi B, Lobner K, Shinohara RT, Mullin GE. Influence of vitamin D on liver fibrosis in chronic hepatitis C: A systematic review and meta-analysis of the pooled clinical trials data. World J Hepatol 2017; 9:278-287. [PMID: 28261385 PMCID: PMC5316848 DOI: 10.4254/wjh.v9.i5.278] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2016] [Revised: 12/14/2016] [Accepted: 01/02/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the relationship between vitamin D and liver fibrosis in hepatitis C-monoinfected or hepatitis C virus (HCV)-human immunodeficiency virus (HIV) co-infected patients. METHODS Pertinent studies were located by a library literature search in PubMed/Embase/Cochrane/Scopus/LILACS by two individual reviewers. Inclusion criteria: (1) studies with patients with HCV or co-infected HCV/HIV; (2) studies with patients ≥ 18 years old; (3) studies that evaluated liver fibrosis stage, only based on liver biopsy; and (4) studies that reported serum or plasma 25(OH)D levels. Studies that included pediatric patients, other etiologies of liver disease, or did not use liver biopsy for fibrosis evaluation, or studies with inadequate data were excluded. Estimated measures of association reported in the literature, as well as corresponding measures of uncertainty, were recorded and corresponding odds ratios with 95%CI were included in a meta-analysis. RESULTS The pooled data of this systematic review showed that 9 of the 12 studies correlated advanced liver disease defined as a Metavir value of F3/4 with 25(OH) D level insufficiency. The meta-analysis indicated a significant association across studies. CONCLUSION Low vitamin D status is common in chronic Hepatitis C patients and is associated with advanced liver fibrosis.
Collapse
Affiliation(s)
- Alia S Dadabhai
- Alia S Dadabhai, Behnam Saberi, Katie Lobner, Gerard E Mullin, Division of Gastroenterology and Hepatology, the Johns Hopkins University School of Medicine, Baltimore, MD 21224, United States
| | - Behnam Saberi
- Alia S Dadabhai, Behnam Saberi, Katie Lobner, Gerard E Mullin, Division of Gastroenterology and Hepatology, the Johns Hopkins University School of Medicine, Baltimore, MD 21224, United States
| | - Katie Lobner
- Alia S Dadabhai, Behnam Saberi, Katie Lobner, Gerard E Mullin, Division of Gastroenterology and Hepatology, the Johns Hopkins University School of Medicine, Baltimore, MD 21224, United States
| | - Russell T Shinohara
- Alia S Dadabhai, Behnam Saberi, Katie Lobner, Gerard E Mullin, Division of Gastroenterology and Hepatology, the Johns Hopkins University School of Medicine, Baltimore, MD 21224, United States
| | - Gerard E Mullin
- Alia S Dadabhai, Behnam Saberi, Katie Lobner, Gerard E Mullin, Division of Gastroenterology and Hepatology, the Johns Hopkins University School of Medicine, Baltimore, MD 21224, United States
| |
Collapse
|
|
39
|
Backstedt D, Pedersen M, Choi M, Seetharam A. 25-Vitamin D levels in chronic hepatitis C infection: association with cirrhosis and sustained virologic response. Ann Gastroenterol 2017; 30:344-348. [PMID: 28469365 PMCID: PMC5411385 DOI: 10.20524/aog.2017.0120] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2016] [Accepted: 12/03/2016] [Indexed: 12/14/2022] Open
Abstract
Background Low serum 25-Vitamin D levels are associated with advanced fibrosis in hepatitis C infection. Vitamin D supplementation has been hypothesized to augment response rates to interferon-based therapy. To date, no investigation has evaluated vitamin D levels during direct-acting antiviral therapy. We aimed to evaluate the prevalence of vitamin D deficiency in cirrhotic and non-cirrhotic cohorts, the predictive value of pretreatment levels for a sustained virologic response, and the changes in 25-OH vitamin D levels during direct-acting antiviral therapy. Methods Two hundred eighteen patients with chronic hepatitis C who completed direct-acting antiviral therapy were consecutively enrolled. Vitamin D levels were measured using chemiluminescence immunoassay, prior to initiation and at completion of therapy. Advanced liver fibrosis (cirrhosis) was determined by biopsy, FibroSURE blood test, or imaging. Results A sustained virologic response was achieved in 79% (n=172) of patients, with 19% (n=44) relapsing. A total of 123 (56.4%) patients were cirrhotic. The prevalence of Vitamin D deficiency (10-20 ng/mL) and severe deficiency (<10 ng/mL) was significantly higher in cirrhotic patients (P=0.04). Pre-treatment vitamin D levels in cirrhotic patients were negatively correlated with Model for End-Stage Liver Disease score, total bilirubin and INR (P<0.05). Neither pretreatment vitamin D level nor the change during therapy was associated with an increased rate of sustained virologic response. Conclusions The prevalence of vitamin D deficiency is higher in hepatitis-C–related cirrhotic cohorts compared to non-cirrhotic patients and correlates with components of hepatic function. Neither pretreatment vitamin D level nor the change during therapy was associated with an increased rate of sustained virologic response.
Collapse
Affiliation(s)
- David Backstedt
- Banner University Liver Disease Center, University of Arizona College of Medicine Phoenix
| | - Mark Pedersen
- Banner University Liver Disease Center, University of Arizona College of Medicine Phoenix
| | - Myunghan Choi
- Banner University Liver Disease Center, University of Arizona College of Medicine Phoenix
| | - Anil Seetharam
- Banner University Liver Disease Center, University of Arizona College of Medicine Phoenix
| |
Collapse
|
|
40
|
Elangovan H, Chahal S, Gunton JE. Vitamin D in liver disease: Current evidence and potential directions. Biochim Biophys Acta Mol Basis Dis 2017; 1863:907-916. [PMID: 28064017 DOI: 10.1016/j.bbadis.2017.01.001] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2016] [Revised: 12/06/2016] [Accepted: 01/02/2017] [Indexed: 01/10/2023]
Abstract
Consistent with its multifaceted nature, growing evidence links vitamin D with hepatic disease. In this review, we summarise the roles of vitamin D in different liver pathologies and explore the clinical utility of vitamin D-based treatments in hepatology. We find that the small number of clinical trials coupled with the profound heterogeneity of study protocols limits the strength of evidence needed to ascribe definite clinical value to the hormone in liver disease. Nevertheless, the experimental data is promising and further bench and bedside studies will likely define a clearer role in hepatic therapeutics.
Collapse
Affiliation(s)
- Harendran Elangovan
- The Garvan Institute of Medical Research, The University of New South Wales (UNSW), Sydney, NSW, Australia
| | - Sarinder Chahal
- The Garvan Institute of Medical Research, The University of New South Wales (UNSW), Sydney, NSW, Australia
| | - Jenny E Gunton
- The Garvan Institute of Medical Research, The University of New South Wales (UNSW), Sydney, NSW, Australia; The Westmead Institute of Medical Research, The University of Sydney, NSW, Australia.
| |
Collapse
|
|
41
|
Loftfield E, O’Brien TR, Pfeiffer RM, Howell CD, Horst R, Prokunina-Olsson L, Weinstein SJ, Albanes D, Morgan TR, Freedman ND. Vitamin D Status and Virologic Response to HCV Therapy in the HALT-C and VIRAHEP-C Trials. PLoS One 2016; 11:e0166036. [PMID: 27832143 PMCID: PMC5104464 DOI: 10.1371/journal.pone.0166036] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2016] [Accepted: 10/11/2016] [Indexed: 12/17/2022] Open
Abstract
More than 150 million people worldwide are chronically infected with hepatitis C virus (HCV) and face higher risk of cirrhosis and hepatocellular carcinoma. Highly effective HCV treatments have recently been developed; however, they are costly and therefore poorly suited for application in resource-limited settings where HCV burden is high. Pegylated-interferon alpha (PEG-IFNα) and ribavirin (RBV) therapy is far less costly, but also less effective. Vitamin D supplementation has been proposed as an inexpensive adjuvant to treatment, however, prior epidemiological evidence on its effectiveness is inconsistent, with little data available among African Americans who naturally have lower vitamin D concentrations. We thus evaluated associations between baseline vitamin D status, measured by circulating 25-hydroxyvitamin D (25(OH)D), which is considered to be the best marker of vitamin D status in humans, and subsequent response to PEG-IFNα/RBV therapy in two large clinical trials that together included 1292 patients infected with HCV genotype 1. We used race-stratified logistic regression models to evaluate multivariable-adjusted associations of 25(OH)D with early virologic response (EVR; 2-log10 HCV RNA decline at week 12) and sustained virologic response (SVR). Among African Americans, we saw no associations. Among European Americans, we saw no association with low vitamin D (≤20 ng/mL) versus sufficient concentrations (20-<30 ng/mL). However, patients with 25(OH)D ≥30 ng/mL were actually less likely to attain EVR (OR = 0.64, 95% CI = 0.43–0.94) than those with sufficient concentrations, with a similar but non-significant association observed for SVR (OR = 0.49, 95% CI = 0.20–1.17).
Collapse
Affiliation(s)
- Erikka Loftfield
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States of America
- * E-mail:
| | - Thomas R. O’Brien
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States of America
| | - Ruth M. Pfeiffer
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States of America
| | - Charles D. Howell
- Department of Medicine, Howard University College of Medicine, Washington, DC, United States of America
| | - Ron Horst
- Heartland Assays, Ames, IA, United States of America
| | - Ludmila Prokunina-Olsson
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States of America
| | - Stephanie J. Weinstein
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States of America
| | - Demetrius Albanes
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States of America
| | - Timothy R. Morgan
- VA Long Beach Healthcare System, Long Beach, CA, United States of America
| | - Neal D. Freedman
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States of America
| |
Collapse
|
|
42
|
Abstract
BACKGROUND Several studies have examined the relationship between vitamin D (VD) and liver disease but none have explored this relationship in adults with normal liver enzymes. Our aim was to explore an independent association of VD with alanine aminotransferase (ALT) in a large sample of the US adults with liver enzymes in normal range (≤39 U/L). METHODS We used the continuous National Health and Nutrition Examination Survey from 2001 to 2006. We excluded individuals with serum ALT>39 U/L. We built linear regression models to estimate unadjusted and adjusted (age, sex, race, diabetes, hypertension, alcohol use, smoking, and body mass index) effect sizes, taking into account the complex probability survey design. RESULTS Of the 12,155 participants, 6635 (54.6%) were women, mean±SD age was 49.9±19.4 years, VD was 21.9±9.2 ng/mL, and ALT was 20.9±6.9 U/L. In unadjusted analysis, VD was significantly associated with serum ALT (0.02 U/L/ng/mL of VD, P=0.007). After adjustment for confounders, VD remained statistically significantly associated with serum ALT levels (0.04 U/L, P<0.001). Similarly, individuals in the highest quartile of VD had significantly higher serum levels of ALT than those in the lowest quartile (unadjusted difference=0.98 U/L, P<0.001; adjusted difference=1.21 U/L, P<0.001). CONCLUSIONS We found a positive association between VD and ALT after excluding individuals with suspected active liver injury (ALT>39 U/L). The underlying mechanisms for this association are not known and needs further study.
Collapse
|
|
43
|
Hu Y, Hu D, Fu R. Letter: effects of hepatitis C infection on the post-lung transplant mortality. Aliment Pharmacol Ther 2016; 44:768. [PMID: 27593426 DOI: 10.1111/apt.13752] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Y Hu
- Department of Infectious Diseases, The Third Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
| | - D Hu
- Department of Infectious Diseases, The Third Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - R Fu
- Department of Infectious Diseases, The Third Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
| |
Collapse
|
|
44
|
Belle A, Gizard E, Conroy G, Lopez A, Bouvier-Alias M, Rouanet S, Peyrin-Biroulet L, Pawlotsky JM, Bronowicki JP. 25-OH vitamin D level has no impact on the efficacy of antiviral therapy in naïve genotype 1 HCV-infected patients. United European Gastroenterol J 2016; 5:69-75. [PMID: 28405324 DOI: 10.1177/2050640616640157] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2015] [Accepted: 02/24/2016] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND AND AIM The impact of 25-OH vitamin D on sustained viral response (SVR) to antiviral therapy and on fibrosis progression in hepatitis C is debated. We assessed the impact of 25-OH vitamin D concentration on the efficacy of antiviral therapy in naïve genotype 1 hepatitis C virus (HCV)-infected patients. METHODS The study population consisted of treatment-naïve genotype 1 patients enrolled in a randomised controlled trial. A total of 516 patients received peginterferon α-2a 180 µg/week plus ribavirin 800 mg/day for 24 weeks. There were 349 patients with undetectable HCV RNA (<50 IU/ml) at week 24 (W24) who were randomised to continue dual therapy (n = 173) or to continue peginterferon alone (n = 176) until week 48. 25-OH vitamin D concentration was measured at baseline in frozen serum. RESULTS A total of 461 patients could be analysed for virologic response at W24, and 285 (119 non-responders at W24 + 166 responders who continued dual therapy until W48) for the impact of SVR. There were 487 patients who could be analysed for fibrosis progression. Metavir fibrosis scores (centralised analysis) were: F1 30%, F2 34%, F3 27% and F4 9%. Median 25-OH vitamin D concentrations were similar in virologic responders (13.5 ng/ml) and in non-responders at W24 (12.6 ng/ml), as well as in patients with SVR (12.8 ng/ml) and without SVR (12.8 ng/ml, 3.99) at W72. Median 25-OH vitamin D concentrations were: F1: 14.30 ng/ml, F2: 13.50 ng/ml, F3: 13.30 ng/ml and F4: 12.80 ng/ml. CONCLUSION In this study, 25-OH vitamin D level has no impact on the efficacy of antiviral therapy in naïve genotype 1 HCV-infected patients.
Collapse
Affiliation(s)
- Arthur Belle
- Inserm U954 and Department of Hepato-Gastroenterology, University Hospital of Nancy Brabois, Université de Lorraine, Vandoeuvre-les-Nancy, France
| | - Emmanuel Gizard
- Inserm U954 and Department of Hepato-Gastroenterology, University Hospital of Nancy Brabois, Université de Lorraine, Vandoeuvre-les-Nancy, France
| | - Guillaume Conroy
- Inserm U954 and Department of Hepato-Gastroenterology, University Hospital of Nancy Brabois, Université de Lorraine, Vandoeuvre-les-Nancy, France
| | - Anthony Lopez
- Inserm U954 and Department of Hepato-Gastroenterology, University Hospital of Nancy Brabois, Université de Lorraine, Vandoeuvre-les-Nancy, France
| | - Magali Bouvier-Alias
- National Reference Center for Viral Hepatitis B, C and Delta, Department of Virology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France; INSERM U955, Créteil, France
| | | | - Laurent Peyrin-Biroulet
- Inserm U954 and Department of Hepato-Gastroenterology, University Hospital of Nancy Brabois, Université de Lorraine, Vandoeuvre-les-Nancy, France
| | - Jean-Michel Pawlotsky
- National Reference Center for Viral Hepatitis B, C and Delta, Department of Virology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France; INSERM U955, Créteil, France
| | - Jean-Pierre Bronowicki
- Inserm U954 and Department of Hepato-Gastroenterology, University Hospital of Nancy Brabois, Université de Lorraine, Vandoeuvre-les-Nancy, France
| |
Collapse
|
|
45
|
Konstantakis C, Tselekouni P, Kalafateli M, Triantos C. Vitamin D deficiency in patients with liver cirrhosis. Ann Gastroenterol 2016; 29:297-306. [PMID: 27366029 PMCID: PMC4923814 DOI: 10.20524/aog.2016.0037] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2015] [Accepted: 03/26/2016] [Indexed: 02/06/2023] Open
Abstract
There is ongoing evidence that vitamin D is related to the pathophysiology of cirrhosis. Although the incidence of vitamin D deficiency in chronic liver diseases and cirrhosis is strongly documented, its pathogenic association with advanced liver fibrosis remains controversial. There is evidence of a significant relation of 25(OH)D levels with the degree of liver dysfunction, considering that an inverse correlation of 25(OH)D levels with both Child-Pugh score and Model for End-Stage Liver Disease has been reported. In addition, vitamin D deficiency has been shown to increase the risk for overall mortality and infections in patients with cirrhosis. Vitamin D deficiency has been also associated with advanced stages of hepatocellular carcinoma and poor prognosis. Finally, there are studies suggesting that patients with chronic hepatitis C and normal vitamin D levels have higher virological response to treatment. However, there are not enough studies conducted in cirrhotic-only populations. The association between vitamin D and cirrhosis demonstrates a great potential for clinical application. The relation between vitamin D deficiency and the degree of liver function, degree of fibrosis and infectious complications could support its use as a prognostic index and a diagnostic tool.
Collapse
Affiliation(s)
| | | | - Maria Kalafateli
- Department of Gastroenterology, University Hospital of Patras, Patras, Greece
| | - Christos Triantos
- Department of Gastroenterology, University Hospital of Patras, Patras, Greece
| |
Collapse
|
|
46
|
Gabr SA, Alghadir AH, Allam AA, Ajarem J, Al-Basher G, Abdel-Maksoud MA, Ghfar AA, Aboud A. Correlation between vitamin D levels and apoptosis in geriatric patients infected with hepatitis C virus genotype 4. Clin Interv Aging 2016; 11:523-33. [PMID: 27217734 PMCID: PMC4862759 DOI: 10.2147/cia.s104599] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Background Vitamin D levels play a pivotal role in most biological processes and differ according to age. A deficiency of vitamin D in chronic hepatitis C (CHC) patients has been shown to be linked with the severity of liver fibrosis, but little is known about the mechanism of this association. Objective In this study, we evaluate the potential interrelation between vitamin D levels, oxidative stress, and apoptosis, based on liver fibrosis in geriatric patients infected with hepatitis C virus (HCV) genotype 4. Subjects and methods A total of 120 adult individuals aged 30–68 years were recruited in this study. Of these, 20 healthy subjects (15 men and five women) with a mean age of 48.3±6.1 years were selected as controls, and 100 patients with a mean age of 47.8±4.9 years with chronic HCV (CHC) who had undergone liver biopsy (80 men and 20 women) were included in this study. Based on liver radiographic (computed tomography, magnetic resonance imaging) and histological Metavir system analyses, the CHC patients were classified into three groups: asymptomatic CHC carriers (n=30), fibrosis (n=25), and cirrhosis (n=45). HCV RNA, HCV genotypes, inflammatory cytokines AFP and TNFα, 25-hydroxyvitamin D (25[OH]D) levels, apoptotic markers single-stranded DNA (ssDNA) and soluble Fas (sFas), and oxidative stress markers nitric oxide (NO) and total antioxidant capacity (TAC) were estimated by using molecular, immunoassay, and colorimetric techniques. Results Approximately 30% of the study population (n=30) were diagnosed as asymptomatic CHC carriers, and 70% of the study population (n=70) had severe fibrosis; these were classified into fibrosis and cirrhosis. There was a significant reduction in 25(OH)D levels and TAC activity, along with an increase in levels of NO, AFP, TNFα, ssDNA, and sFas in fibrosis and cirrhosis subjects compared with those of asymptomatic CHC carriers and health controls. The deficiency in 25(OH)D levels correlated positively with sFas, ssDNA, AFP, TNFα, NO, and TAC, and negatively with age, sex, liver function, body mass index, homeostatic model assessment – insulin resistance, HCV RNA, and viral load. Significant intercorrelation was reported between serum 25(OH)D concentrations and apoptotic and oxidative markers, which suggested progression of liver pathogenesis and fibrogenesis via oxidative and apoptotic mechanisms. Conclusion The data showed that vitamin D status was significantly correlated with pathogenesis and fibrogenesis of the liver in geriatric patients infected with HCV genotype 4. The deficiency in 25(OH)D levels was shown to have a pivotal role in the pathogenesis of liver via apoptotic, oxidative stress, and inflammatory mechanistic pathways. The data point to adequate vitamin D levels being recommended for a good response to treatment strategies, especially in older CHC patients.
Collapse
Affiliation(s)
- Sami A Gabr
- Rehabilitation Research Chair, College of Applied Medical Sciences, King Saud University, Riyadh, Kingdom of Saudi Arabia; Department of Anatomy, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Ahmad H Alghadir
- Rehabilitation Research Chair, College of Applied Medical Sciences, King Saud University, Riyadh, Kingdom of Saudi Arabia
| | - Ahmed A Allam
- Zoology Department, College of Science, King Saud University, Riyadh, Saudi Arabia; Zoology Department, Faculty of Science, Beni-Suef University, Beni Suef, Egypt
| | - Jamaan Ajarem
- Zoology Department, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Ghada Al-Basher
- Zoology Department, College of Science, King Saud University, Riyadh, Saudi Arabia
| | | | - Ayman A Ghfar
- Department of Chemistry, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Alaa Aboud
- Internal Endemic Medicine Department, College of Medicine, Beni-Suef University, Beni Suef, Egypt
| |
Collapse
|
|
47
|
Optimal vitamin D plasma levels are associated with lower bacterial DNA translocation in HIV/hepatitis c virus coinfected patients. AIDS 2016; 30:1069-74. [PMID: 27032111 DOI: 10.1097/qad.0000000000001007] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
OBJECTIVE Vitamin D has been linked to the immune response modulation and the integrity of the intestinal mucosal barrier. Therefore, vitamin D might be involved in bacterial translocation related to HIV infection. Our major aim was to analyze the association between plasma levels of 25-hydroxy-vitamin D [25(OH)D] and bacterial 16S ribosomal DNA (bactDNA) in 120 HIV/hepatitis c virus (HCV) coinfected patients. DESIGN Cross-sectional study. METHODS Plasma 25(OH)D levels were quantified by enzyme immunoassay. The vitamin D status was defined as deficient (<25 nmol/l), insufficient (25-74 nmol/l), and optimal (≥75 nmol/l) plasma levels. Plasma bactDNA levels were measured by quantitative real-time PCR. For bactDNA levels the cutoffs used were as follows: low [<p25th (46 copies/μl)], moderate [p25th to p50th (78 copies/μl)], high [p50th to p75th (159 copies/μl)], and very high (>p75th). RESULTS Eighteen (15%) patients had 25(OH)D deficiency, 93 (77.5%) had insufficiency and nine (7.5%) had 25(OH)D optimal values. The bactDNA levels were lower in patients with 25(OH)D at least 75 nmol/l [37 copies/μl] than in patients with 25(OH)D insufficiency [84.2 copies/μl; P = 0.042]. Conversely, low bactDNA levels (<p25th) were found in 66.7% of patients with 25(OH)D optimal levels, whereas bactDNA levels above p25th were found only in 11.1% of them (P = 0.029). The plasma 25(OH)D not less than 75 nmol/l was associated with low bactDNA levels (<p25th) [adjusted OR = 8.13 (95% confidence interval = 1.82; 36.67); P = 0.006)]. The patients with optimal vitamin D status [25(OH)D ≥75 nmol/l] had lower plasma levels of CCL7 (P = 0.047) and basic fibroblast growth factor (P = 0.042). CONCLUSION The optimal vitamin D status was associated with low bacterial translocation and inflammation in HIV/HCV coinfected patients.
Collapse
|
|
48
|
Drori A, Shabat Y, Ben Ya'acov A, Danay O, Levanon D, Zolotarov L, Ilan Y. Extracts from Lentinula edodes (Shiitake) Edible Mushrooms Enriched with Vitamin D Exert an Anti-Inflammatory Hepatoprotective Effect. J Med Food 2016; 19:383-9. [DOI: 10.1089/jmf.2015.0111] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Affiliation(s)
- Ariel Drori
- Liver Unit, Department of Medicine, Hadassah - Hebrew University Medical Center, Jerusalem, Israel
| | - Yehudit Shabat
- Liver Unit, Department of Medicine, Hadassah - Hebrew University Medical Center, Jerusalem, Israel
| | - Ami Ben Ya'acov
- Liver Unit, Department of Medicine, Hadassah - Hebrew University Medical Center, Jerusalem, Israel
| | - Ofer Danay
- Migal, Galilee Research Institute, Kiryat Shmone, Israel
| | - Dan Levanon
- Migal, Galilee Research Institute, Kiryat Shmone, Israel
| | - Lidya Zolotarov
- Liver Unit, Department of Medicine, Hadassah - Hebrew University Medical Center, Jerusalem, Israel
| | - Yaron Ilan
- Liver Unit, Department of Medicine, Hadassah - Hebrew University Medical Center, Jerusalem, Israel
| |
Collapse
|
|
49
|
Atsukawa M, Tsubota A, Shimada N, Yoshizawa K, Abe H, Asano T, Ohkubo Y, Araki M, Ikegami T, Okubo T, Kondo C, Osada Y, Nakatsuka K, Chuganji Y, Matsuzaki Y, Iwakiri K, Aizawa Y. Effect of native vitamin D3 supplementation on refractory chronic hepatitis C patients in simeprevir with pegylated interferon/ribavirin. Hepatol Res 2016; 46:450-8. [PMID: 26289410 DOI: 10.1111/hepr.12575] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Revised: 08/11/2015] [Accepted: 08/11/2015] [Indexed: 02/08/2023]
Abstract
AIM Protease inhibitors with pegylated interferon (PEG IFN)/ribavirin improve a sustained virological response (SVR) rate to approximately 90% in chronic hepatitis C genotype 1b patients with IL28B rs8099917 genotype TT, but yield only approximately 50% in those with the unfavorable non-TT. Among such treatment-refractory patients, serum vitamin D levels could influence the SVR rate. This randomized controlled trial was conducted to assess the effect of native vitamin D supplementation in simeprevir with PEG IFN/ribavirin for 1b patients with non-TT. METHODS Patients were randomly assigned to receive simeprevir (100 mg/day) for 12 weeks plus PEG IFN/ribavirin for 24 weeks (control group, n = 58), or vitamin D (2000 IU/day) for 16 weeks including a lead-in phase plus PEG IFN/ribavirin for 24 weeks (vitamin D group, n = 57). The primary end-point was sustainably undetectable viremia 24 weeks after the end of treatment (SVR). RESULTS SVR rates were 37.9% in the control group and 70.2% in the vitamin D group. In subgroup analysis, SVR rates of prior null responders were 11.8% and 54.5%, respectively. SVR rates for advanced fibrosis were 28.6% and 65.4%. SVR rates for patients with vitamin D3 deficiency at the baseline were 25.0% in the control group and 66.7% in the vitamin D group. Overall, the SVR rate was significantly higher in patients with high serum 25(OH)D3 levels at the beginning of combination therapy than in those with low serum 25(OH)D3 levels. CONCLUSION Native vitamin D3 supplementation improved SVR rates in simeprevir with PEG IFN/ribavirin for chronic hepatitis C genotype 1b patients with refractory factors.
Collapse
Affiliation(s)
- Masanori Atsukawa
- Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai
| | - Akihito Tsubota
- Core Research Facilities for Basic Science, Research Center for Medical Sciences, Jikei University School of Medicine, Tokyo
| | | | | | - Hiroshi Abe
- Jikei University School of Medicine Katsushika Medical Center
| | - Toru Asano
- Tokyo Metropolitan Bokutoh Hospital, Tokyo
| | | | | | | | - Tomomi Okubo
- Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai
| | - Chisa Kondo
- Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai
| | | | | | | | | | | | - Yoshio Aizawa
- Jikei University School of Medicine Katsushika Medical Center
| |
Collapse
|
|
50
|
Amrein K, McNally JD, Dobnig H, Pieber TR. High-dose cholecalciferol in critically ill patients with liver cirrhosis. J Intern Med 2016; 279:309-10. [PMID: 26707009 DOI: 10.1111/joim.12457] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- K Amrein
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - J D McNally
- Division of Critical Care, Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada
| | - H Dobnig
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Graz, Austria.,Schilddrüsen-Endokrinologie-Osteoporose Institut Dobnig, Graz, Austria
| | - T R Pieber
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Graz, Austria.,Joanneum Forschungsgesellschaft GmbH, Graz, Austria
| |
Collapse
|