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Abbreviations 1,25(OH)2D): 1, 25-dihydroxyvitamin D; 25(OH)D: 25-hydroxyvitamin D; 95% CI: 95% confidence interval; ALT: Alanine aminotransferase; AST: Aspartate transaminase; BMI: Body mass index; CYP27B1: cytochrome P450 family 27 subfamily B member 1; CYP2R1: Cytochrome P450 family 2 subfamily R member 1; DAA: Direct-acting agents; DHCR7: 7-dehydrocholesterol reductase; DNA: Deoxyribonucleic Acid; EVR: Early virologic response; GC: Vitamin D binding protein; GWAS: Genome-wide association studies; HCV: Hepatitis C
Source publication
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 t...
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Citations
... 10 Vitamin D not only improves bone mineralization but also reverses hepatic fibrosis and suppresses hepatitis C viral replication and thus improves virological response in patients with chronic hepatitis C with and without cirrhosis. 11 The purpose of this study is to establish role of 25-OH Vitamin D in patients with hepatitis C infection by comparing the frequency of RVR after 4 weeks in patients being treated with sofosbuvir, ribavirin plus vitamin D and sofosbuvir plus ribavirin only. Role of vitamin D has been postulated to improve the treatment outcomes in combination with interferons and not with the direct-acting antiviral agents like sofosbuvir which are the standard of care according to new guidelines. ...
Background: Hepatitis C is the leading cause of liver damage that lead to death if left untreated. Sofosbuvir has recently attained enormous success due to high rate of virological response. Recent studies have shown that addition of vitamin D to antiviral therapy improves the efficacy of treatment in patients with Hepatitis C. Objective: To compare the frequency of virological response in hepatitis C patients treated with vitamin D along with sofosbuvir plus ribavirin to those treated with sofosbuvir plus ribavirin only Study Design: Randomized-controlled-trial Place and Duration of Study: Department of Medicine, Pak Emirates Military Hospital, Rawalpindi from 1st November 2017 to 30th April 2018. Methodology: One hundred patients of chronic hepatitis C were included. Patients were randomly divided into two groups; group A receiving vitamin D along with sofosbuvir plus ribavirin and group B receiving sofosbuvir plus ribavirin therapy only. Patients were treated for 6 months and their RVR was monitored. Results: The mean age of patients in combination group was 39.0±12.92 years and in control group were 36.66±13.80years. After 4 weeks, RVR (no HCV RNA detected on PCR) was achieved in 31 (62%) cases in combination group while in 19 (38%) cases there was still HCV RNA present. In control group, RVR could be achieved in 18 (36%) cases while in 32 (64%) cases, RVR could not be achieved. The difference was significant between both groups (p<0.05). Conclusion: The addition of vitamin D can help in achieving RVR in >50% cases within 4 weeks. So addition of vitamin D in standard therapy may help to improve the quality of treatment. Keywords: Rapid virological response, Hepatitis C, 25-OH vitamin D, Sofosbuvir, Ribavirin
... DNA stock aliquots were diluted to a concentration of 50 ng/µl and were frozen until needed for PCR assays. We selected four candidate genes containing 5 SNPs according to the following criteria: (1) biological importance in vitamin D metabolism and transportation (2) evidence of a significant association to vitamin D deficiency according to previous GWAS reports and (3) having significant relation with vitamin D deficiency in the population who were genetically close and environmentally similar to Bangladeshi population 14,[29][30][31] . The selected genes and SNPs were GC (rs7041T > G, rs4588C > A), CYP2R1 (rs206793A > G), CYP27B1 (rs10877012 A > C) and DHCR7 (rs12785878G > T). ...
We conducted an observational study to assess the prevalence and risk factors of vitamin D deficiency in 12–24 months old children living in urban and rural Bangladesh. Serum 25-hydroxyvitamin D (free 25(OH)D) level, socio-demographic status, anthropometric status, dietary intake, exposure to sunlight and single nucleotide polymorphisms in vitamin-D pathway genes were measured in 208 children. Vitamin D deficiency (free 25(OH)D < 50 nmol/l) was reported in 47% of the children. Multivariable logistic regression model identified duration to sunlight exposure (regression coefficient, β = − 0.01; 95% CI 0.00, − 0.02; p-value < 0.05), UV index (β = − 0.36; 95% CI 0.00, − 0.02; p-value < 0.05) and breast-feeding (β = − 1.15; 95% CI − 0.43, − 1.86; p-value < 0.05) to be negatively associated with vitamin D deficiency. We measured the role of single nucleotide polymorphisms in pathway genes ( GC -rs7041 T > G, rs4588 C > A, CYP2R1 -rs206793 A > G, CYP27B1 -rs10877012 A > C and DHCR7 -rs12785878 G > T) and found statistically significant differences in serum vitamin D levels between various genotypes. SNPs for CYP27B1 (CA & CC genotype) had statistically significant positive association (β = 1.61; 95% CI 2.79, 0.42; p-value < 0.05) and TT genotype of GC -rs7041 had negative association (β = − 1.33; 95% CI − 0.02, − 2.64; p-value < 0.05) with vitamin-D deficiency in the surveyed children.
... Many polymorphisms were identified in studies examining the VDR gene, i.e., ApaI, TaqI, FokI and BsmI polymorphisms [4]. There are studies investigating the relationship between Vitamin D levels and VDR gene polymorphisms, and different results have been obtained in different populations [5][6][7][8][9]. ...
... There are many studies regarding the correlation between VDR gene polymorphisms and vitamin D levels in the world and in Turkey; nevertheless, the results were inconsistent with each other. The relationship between Vitamin D levels and polymorphisms in the VDR gene was demonstrated in certain studies [5][6][7][8][9][22][23][24][25]. Contrarily, studies with no evident correlation on this issue were conducted both abroad and in Turkey. ...
Background/Aim: Vitamin D exerts its effects in the body through its receptors. Polymorphisms in vitamin D Receptor (VDR) gene are known to cause certain diseases and affect vitamin D levels. In this study, we planned to examine the relationship between vitamin D levels and Vitamin D gene polymorphisms among children.
Methods: The study group included 124 healthy children living in the same region. Vitamin D (VitD), Parathyroid Hormone (PTH), Alkaline phosphatase (ALP), Calcium (Ca), Phosphorus (P) and Magnesium (Mg) were examined in the blood samples taken. In terms of measured Vitamin D levels, children were divided into group 1 (Vitamin D < 20 ng/mL) and group 2 (Vitamin D ≥ 20 ng/mL). Deoxyribonucleic Acid (DNA) was isolated from the serum sample, VDR ApaI and TaqI polymorphisms were determined by Polymerase Chain Reaction (PCR) method, and comparisons were made between groups.
Results: The overall mean age of the children included in the study was 8.11 (4.98) years. The mean ages of participants in Groups 1 and 2 were 9.38 (4.87) years and 6.38 (4.62) years, respectively (P=0.091). The mean vitamin D levels of Groups 1, 2 and overall were 13.82 (3.29) ng/mL, 33.96 (20.47) ng/mL, and 23.49 (21.54) ng/mL, respectively (P=0.509). The two groups were similar in terms of serum ALP, PTH, Ca, Mg and P levels (P>0.05 for all). VDR polymorphisms were found to have no effect on Vitamin D levels.
Conclusion: In our study, no relationship was found between the genotypes of ApaI and TaqI polymorphisms and Vitamin D levels. This study is important in terms of remarking the fact that Vitamin D deficiency is still a public health problem and its contributions to VDR gene polymorphism research.
... For example, VDR gene polymorphism did not correlate with rapid virological response and SVR achievement in HCV patients [74]. In addition, the VDBP, CYP2R1, and CYP27B1 polymorphisms did not play any role in the treatment outcomes of HCV infection [85]. ...
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.
... Genetic variations in CYP27A1, CYP2R1 and CYP27B1 have been found to be related to various immune-mediated diseases, such as multiple sclerosis [23], type 1 diabetes mellitus [24], autoimmune thyroid diseases [25], and hepatitis B virus (HBV) infection [26,27]. These variations have also been observed to be involved in the progression of liver fibrosis [28] and the therapeutic response [29][30][31] to chronic HCV infection. However, there are limited data on the association between polymorphisms of these vitamin D pathway genes and HCV infection outcomes. ...
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.
... However, 1,25(OH) 2 D 3 can be decomposed by 1,25-hydroxyvitamin-D3-24-hydroxylase encoded by CYP family 24 subfamily A member 1 (CYP24A1) gene, and then excreted through bile to maintain the balance of vitamin D metabolism in vivo. Studies have reported that SNPs involved in the pathway of vitamin D synthetic, including CYP2R1, CYP27B1, 7dehydrocholesterol reductase (DHCR7), and vitamin D receptor (VDR) genes, are associated with complications of HCV infection or Peg-IFN treatment response (de Azevedo et al., 2017;Lange et al., 2011;Thanapirom et al., 2017). 24-hydroxylase is a rate-limiting enzyme in the metabolism of vitamin D and plays an important role in maintaining the balance of vitamin D metabolism. ...
Background and aims
It has been demonstrated that 1,25-hydroxyvitamin-D3-24-hydroxylase, encoded by CYP24A1 gene, is a key enzyme that neutralizes the active vitamin D3 metabolite 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in response to hepatitis C virus (HCV) infection. This study aimed to investigate whether CYP24A1 genetic variation is associated with HCV infection outcomes.
Methods
848 HCV chronically infected subjects, 507 natural clearance subjects, and 1017 uninfected controls were enrolled. Nine single nucleotide polymorphisms (SNPs) in theCYP24A1 gene were genotyped using the Sequenom MassARRAY platform.
Results
After adjusting for age, gender, and routes of infection, logistic regression analyses showed that rs6013897-A was associated with an elevated risk of HCV infection (P < 0.05). In addition, this study has also demonstrated that rs6068816-T significantly reduced the risk of chronic HCV infection, while rs3787557-C, rs6022999-G, and rs2248359-T significantly increased the risk of chronic HCV infection (all P < 0.05). Haplotype analysis suggested that, compared to the most frequent Trs6068816Trs3787557Ars6022999Crs2248359 haplotype, the CTGT haplotype (adjusted OR = 1.376, 95% CI = 1.092-1.735, P = 0.007) and CCAC haplotype (adjusted OR=1.483, 95% CI=1.139-1.929, P = 0.003) were associated with an increased risk of chronic HCV infection.
Conclusion
These findings indicate that SNPs in CYP24A1 gene may contribute to the risk of HCV infection and chronic HCV infection among a high-risk Chinese population.
... No impact was observed between vitamin D levels and response to antiviral therapy [30]. Studies have also evaluated genetic polymorphisms related to vitamin D cascade in Thai population and have observed that polymorphism in the DHCR7 gene may be a predictive marker of response to dual therapy (PEG-IFN + ribavirin) in a patient with HCV genotype 1 [31]. ...
... A prospective cohort of 398 genotype 1-infected patients from Germany showed a higher prevalence of DHCR7 TT related to SVR [40]. Another study including 623 Thai patients also found an association with lower SVR rates compared with those with the DHCR7 TT/TG genotype, whereas the SVR rate did not differ in HCV nongenotype 1-infected patients [41]. ...
... A genetic influence in the second step was found in G1 HCV-infected patients from Germany, whereby polymorphisms of CYP27B1-1260, such as AA or CA genotype, were related to a higher SVR rate compared with those with the AC and CC genotype [42]. Meanwhile, in a cohort of 238 white patients with CHC infection treated with pegIFN/RBV, there was no correlation between CYP27B1-1260 rs10877012 polymorphism and response to therapy [43], which is in agreement with Thanapirom et al. [41]. ...
... In the final step, a genome-wide association study cohort of ∼ 30 000 European individuals identified the GC variants associated with lower 25(OH)D concentrations and strongly correlated with lower levels of DBP [44], whereas no association was found between the polymorphisms of GC and treatment outcome, no matter the genotype, in a study of 623 Thai patients [41]. Recently, the first cross-sectional study on the quantitative hepatic expression of VDR in G1CHC reported that VDR expression was reduced according to the severity of liver fibrosis and necroinflammatory activity after correcting for well-known metabolic and histological risk factors [45]. ...
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.
... The change in the VDR protein structure led to altered biological functions of vitamin D and was involved in carcinogenesis (Arai et al., 1997). Thanapirom et al. (2017) reported that when 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), the DHCR7 polymorphism could be a pre-treatment predictive marker for response to PEG-IFN-based therapy in chronic HCV genotype 1 infection. ...
Hepatocellular carcinoma (HCC) is a primary liver malignancy, and is now the six most common in between malignancies. Early diagnosis of HCC with prompt treatment increases the opportunity of patients to survive. With the advances in understanding the molecular biology of HCC, new therapeutic strategies to treat HCC have emerged. There is a growing consensus that vitamins are important for the control of various cancers. Biochemical evidence clearly indicates that HCC cells are responsive to the inhibitory effect of vitamin D, vitamin D analogues and vitamin K. In this review, we summarize the mechanisms used by vitamin D and K to influence the development of HCC and the latest development of vitamin analogues for potential HCC therapy.
Abstract Background Vitamin D (VD) is important in hepatic fibrogenesis in animal models and human studies. VD deficiency is associated with liver fibrosis progression. Metabolic dysfunction of the liver, as an intermediate organ for VD metabolism, contributes partly to this deficiency. We hypothesized that improving hepatic fibrosis and inflammation in chronic hepatitis C (CHC) patients after eradication with direct-acting antivirals (DAA) would increase 25-hydroxyVD [25(OH)VD] levels. Methods Eighty CHC patients (17 chronic hepatitis, and 63 cirrhosis) were enrolled. Baseline characteristics, hepatitis C viral load (VL), genotypes, liver enzymes and liver stiffness measurements (LSM) were assessed at baseline. Blood samples for 25(OH)VD and the procollagen type III N-terminal peptide (P3NP) were collected at baseline, 24 and 48 weeks. LSMs were re-evaluated at 48 weeks. Serum 25(OH)VD levels
