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Hepatitis B virus and Vitamin D - many studies


Vitamin D targets Hepatitis B virus - Sept 2021

Vitamin D signaling inhibits HBV activity by directly targeting the HBV Core promoter
J Biol Chem . 2021 Sep 22;101233. doi: 10.1016/j.jbc.2021.101233
Shivaksh Ahluwalia 1, Divya Choudhary 2, Purnima Tyagi 3, Vijay Kumar 3, Perumal Vivekanandan 4

Clinical and epidemiological studies support a role for vitamin D in suppressing hepatitis B virus (HBV). This antiviral role of vitamin D is widely attributed to Vitamin D Receptor (VDR)/Retinoid X Receptor (RXR)-mediated regulation of host immunomodulatory genes through Vitamin D Response Elements (VDREs) in their promoters. Here, we investigated the ability of calcitriol (1α,25(OH)2D3, metabolically activated Vitamin D) to directly regulate HBV activity through this signaling pathway. We observed that calcitriol selectively inhibited only the HBV-core promoter without affecting the HBV-PreS1, HBV-PreS2/S, or HBx promoters. We then identified a VDRE-cluster in the HBV-core promoter that is highly conserved across most HBV genotypes. Disruption of this VDRE-cluster abrogated calcitriol-mediated suppression of the HBV-core promoter.
Furthermore, we showed VDR interacts directly with the VDRE-cluster in the HBV-core promoter independent of RXR. This demonstrates that calcitriol inhibits HBV-core promoter activity through a non-canonical calcitriol-activated VDR-pathway. Finally, we observed that calcitriol suppressed expression of the canonical HBV-core promoter transcripts, pregenomic RNA and precore RNA in multiple HBV cell culture models. Additionally, calcitriol inhibited the secretion of HBeAg and HBsAg (HBV-encoded proteins linked to poor disease prognosis), without affecting virion secretion.
Our findings

  • (a) identify VDR as a novel regulator of HBV-core promoter activity,
  • (b) explain at least in part the correlation of vitamin D levels to HBV activity in clinical studies,
  • (c) have implications on the potential use of vitamin D along with anti-HBV therapies, and
  • (d) lay the groundwork for studies on vitamin D-mediated regulation of viruses through VDREs in virus promoters.

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Hepatitis B strongly associated with low Vitamin D - April 2021

Fitting logistic regression models to assess vitamin D deficiency with clinical parameters in chronic hepatitis B patients
Infectious Disease Modelling 2021, 6: 612-617
Freshteh Osmani, Ghodsiyeh Azarkar

Table of data made by VitaminDWiki

Level %
< 10 ng/mL63%
10 to 20 ng/mL47%
>20 ng19%

Statistical models provide a quantitative structure with which clinicians can evaluate their hypotheses to explain patterns in observed data and generate forecasts. In contrast, vitamin D is an important immune modulator that plays an emerging role in liver diseases such as chronic hepatitis B (CHB). Therefore, we quantified 25(OH)D3 serum levels in 292 CHB patients tested for their association with clinical parameters. Of 292 patients, 69 (63%), 95 (47%), and 39 (19%) had severe vitamin D deficiency (25(OH)D3 < 10 ng/mL), vitamin D insufficiency (25(OH)D3 10 and < 20 ng/mL), or adequate vitamin D serum levels (25(OH)D3 20 ng/mL), respectively. In both univariate and multivariate analyses, zinc serum level was a strong predictor of low 25(OH)D3 serum levels (P < 0.001). Results of fitted models showed that lower vitamin D levels were significantly associated with: younger age, lower uric acid levels, HBeAg-positive status, lower calcium levels (p < 0.05). Vitamin D deficiency (<20 ng/ml) or severe deficiency (<10 ng/ml) was observed more frequently among HBV patients (52%). Vitamin D deficiency was observed in most CHB patients. Generally, our results recommend that substitution of vitamin D can be a substitution method in the treatment of patients with HBV-associated disorders.
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Occult and Chronic Hepatitis B Infection: Relation of Viral Load to Serum Level of 25 Hydroxy Vitamin D - 2016

Int.J.Curr.Microbiol.App.Sci (2016) 5(7): 660-669
Vitamin D vs HGV - log scale
Image
Mervat Mashaly1 *, Eman EL Sayed1 , Gehaan A. Shaker2 , Rokiah Anwar3, Neven Farouk Abbas3 , Sahar Zakaria4 and Enaase A.M.E. Barakat3
1Clinical Pathology Department, Faculty of Medicine, Mansoura University-Egypt
2 Physiology department, Faculty of Medicine, Mansoura University-Egypt
3 Internal Medicine Department, Faculty of Medicine, Mansoura University-Egypt
4 Tropical Medicine Department, Faculty of Medicine, Mansoura University-Egypt

Introduction
Hepatitis B vaccine is available since 1982, but hepatitis B virus (HBV) infection is still a major public health problem worldwide because of its significant mortality and morbidity. Worldwide, almost 240 million individual are chronically infected with HBV (WHO, 2015). It is the reason for around half of the world's cases of hepatocellular carcinoma (HCC) and around 30% of all cases of liver cirrhosis, causing more than 780,000 deaths for every year (ElSeraq, 2011) and (Gish and Locarnini, 2007). In Egypt, hepatitis B surface antigen (HBsAg) prevalence is of moderate endemicity (2–8%). Furthermore, almost 2-3 million Egyptians are chronic carriers of HBV (Attia, 1998).

Recent evidence from various lines of research suggested that low levels of vitamin D are associated with high levels of hepatitis B virus (HBV) replication in chronic hepatitis B (CHB) infection. However, the relationship between vitamin D and occult hepatitis B infection (OBI) remains unclear. To investigate the pattern of 25 hydroxy vitamin D levels in patients with OBI, we compared serum level of vitamin D among 52 patients with CHB infection, 16 patients with OBI and 34 age & sex matched healthy control. Hepatitis B envelope (HBe) antigen was assayed among CHB patients. Also, we quantified HBV DNA viral load among both CHB and OBI groups by using Real time PCR. We found that serum level of vitamin D was significantly higher in patients with OBI than those with CHB infection but it was insignificantly differ from healthy control. Patients with HBe Ag negative had a significantly higher serum level of vitamin D than those with HBe Ag positive. Serum level of vitamin D was inversely correlated with HBV DNA viral load. It could be concluded that adequate levels of vitamin D may be one of the factors limiting the replication of HBV and decreasing viral load in patients with OBI

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Serum 25-hydroxyvitamin D status in pregnant women with chronic hepatitis B virus infection. - Aug 2016

J Infect Dev Ctries. 2016 Aug 31;10(8):851-856. doi: 10.3855/jidc.6600.
Gao XR1, Wang CM, Wang WJ, Han GR, Zhang JQ.
1Medical School Southeast University, Nanjing, Jiangsu, China. gxr871230 at 126.com.

INTRODUCTION:
Maternal 25-hydroxyvitamin D [25(OH)D] deficiency has a negative influence on the health of the mother and the developing fetus. The aim of this study was to assess serum 25(OH)D status and its relationship to virologic and biochemical parameters in pregnant women with chronic hepatitis B virus (HBV) infection.
METHODOLOGY:
Serum 25(OH)D levels among 142 pregnant women with chronic HBV infection and 251 healthy pregnant women were measured using enzyme-linked immunosorbent assay.
RESULTS:
The mean±SD values for serum 25(OH)D levels were 13.63±5.5 ng/mL in healthy pregnant women and 12.05±3.3 ng/mL in pregnant women with chronic HBV infection (p < 0.01). Serum 25(OH)D levels were associated with seasonal variation in healthy pregnant women (p = 0.01); however, similar results were not observed in pregnant women with chronic HBV infection (p = 0.10). Furthermore, multivariate analysis indicated that only ALT level was independently associated with severe vitamin D deficiency (p = 0.01). A significant positive correlation was found between serum 25(OH)D level and ALT level in pregnant women with chronic HBV infection (r = 0.32; p < 0.001).
CONCLUSIONS:
Vitamin D levels were lower in pregnant women with chronic HBV infection compared with healthy pregnant women. Vitamin D supplementation can be routinely recommended for pregnant women in China.


HBV had lower level of vitamin D, until Antivral Treatment cured the HBV AND raised Vit D levels - Oct 2015

Sustained suppression of viral replication in improving vitamin D serum concentrations in patients with chronic hepatitis B.
Sci Rep. 2015 Oct 21;5:15441. doi: 10.1038/srep15441.
Chen EQ1,2, Bai L1,2, Zhou TY1,2, Fe M1,2, Zhang DM1,2, Tang H1,2.
1Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.
2Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan 610041, PR China.


Image Image

Recently, the role of vitamin D in chronic hepatitis B (CHB) has attracted a lot attention. In this study, 128 naïve CHB patients (91 with positive HBeAg, 37 with negative-HBeAg) were enrolled, and 128 volunteers without liver diseases were enrolled as controls. Compared to that of healthy controls, the mean level of 25(OH)D3 in CHB patients was significantly lower; and the percent of patients with sufficient 25(OH)D3 (≥20 ng/mL) was also significantly lower than that of healthy controls. Among those CHB patients, the level of 25(OH)D3 was negatively correlated with the serum HBV-DNA level. Additionally, the level of 25(OH)D3 was significantly lower in HBeAg-positive patients than that in HBeAg-negative patients.
After the patients went through the long-term antiviral treatments, both the mean level of 25(OH)D3 and the percent of patients with sufficient 25(OH)D3 increased significantly.
Additionally, patients who were HBeAg free after the treatment also had much higher 25(OH)D3 level than those with persistent positive HBeAg. All those data suggested that the low vitamin D serum level was dangerous for CHB patients, and the level of 25(OH)D3 was highly negatively correlated with HBV-DNA levels. Effective antiviral therapy might increase the level of vitamin D in CHB patients.

PMID: 26486883 PMCID: PMC4614353 DOI: 10.1038/srep15441
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BMC Infect Dis. 2016 Sep 23;16(1):507.
Hoan NX1,2, Khuyen N3, Binh MT1,2, Giang DP1,2, Van Tong H1,2, Hoan PQ4, Trung NT2,4, Anh DT5, Toan NL2,6, Meyer CG1,2, Kremsner PG1,2, Velavan TP1,2,7, Song LH8,9.
1Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.
2Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam.
3Department of Infectious Diseases, Duc Giang Hospital, Hanoi, Vietnam.
4Department of Molecular Biology, 108 Military Central Hospital, Hanoi, Vietnam.
5Department of Infectious Diseases, Vietnam Military Medical University, Hanoi, Vietnam.
6Department of Pathophysiology, Vietnam Military Medical University, Hanoi, Vietnam.
7Fondation Congolaise pour la Recherche Medicale, Brazzaville, Republic of Congo.
8Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam. lehuusong at 108-icid.com.
9Institute of Clinical Infectious Diseases, 108 Military Central Hospital, Tran Hung Dao Street N1, Hai Ba Trung District, Hanoi, Vietnam. lehuusong at 108-icid.com.

BACKGROUND:
As an immune modulator, vitamin D is involved in various pathophysiological mechanisms in a plethora of diseases. This study aims to correlate the vitamin D deficiency status and clinical progression of liver diseases associated with hepatitis B virus (HBV) infection in patients in Vietnam and to compare it to healthy controls.
METHODS:
We quantified the levels of total vitamin D [25-(OH) D2 and D3] in serum samples from 400 HBV patients (chronic hepatitis B infection CHB, n = 165; HBV-associated liver cirrhosis [LC], n = 127; HBV-associated hepatocellular carcinoma [HCC], n = 108) and 122 unrelated healthy controls (HC). Univariate and multivariate analyses were performed in order to determine the association between vitamin D levels and distinct clinical parameters.
RESULTS:
The prevalence of vitamin D inadequacy (<30 ng/mL) was high among healthy individuals (81.7 %) as well as in HBV patients (84.3 %). Vitamin D deficiency (<20 ng/ml) or severe deficiency (<10 ng/ml) was observed more frequently among HBV patients (52 %) and subgroups (CHB, 47.8 %; LC, 54.4 %; HCC, 55.3 %) compared to the control group (32.5 %) (P < 0.001). Vitamin D levels and HBV-DNA load were strongly and inversely correlated (rho = -0.57, P < 0.0001). Multivariate regression analysis also revealed an independent association of HBV-DNA loads with low vitamin D levels (P = 0.0004). In addition, reduced vitamin D levels were associated with significant clinical progression of LC (Child-Pugh C versus Child-Pugh A, P = 0.0018; Child-Pugh C versus Child-Pugh B, P = 0.016).
CONCLUSIONS:
Vitamin D deficiency was observed in the majority of HBV-infected patients and associated with adverse clinical outcomes. Our findings suggest that substitution of vitamin D may be a supportive option in the treatment of chronic liver diseases, in particular of HBV-associated disorders.


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PMID: 27659316 DOI: 10.1186/s12879-016-1836-0
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Created by admin. Last Modification: Sunday September 26, 2021 14:31:32 GMT-0000 by admin. (Version 31)

Attached files

ID Name Comment Uploaded Size Downloads
16284 HBV Sept 2021_compressed.pdf admin 26 Sep, 2021 14:29 991.55 Kb 17
15524 HEPA B April 2021.pdf PDF 2021 admin 29 Apr, 2021 01:05 257.19 Kb 90
7110 HBV F3.jpg admin 26 Sep, 2016 15:10 28.84 Kb 2547
7109 HBV T2.jpg admin 26 Sep, 2016 15:10 38.32 Kb 2403
7108 hepatitis B BMC.pdf admin 26 Sep, 2016 15:02 580.28 Kb 1504
7080 Vit D after AVT.jpg admin 15 Sep, 2016 11:13 15.20 Kb 2488
7079 CHB.jpg admin 15 Sep, 2016 11:13 15.33 Kb 2553
7078 Sustained suppression HVB.pdf PDF 2016 admin 15 Sep, 2016 11:13 870.01 Kb 1148
6900 HBV occult.jpg admin 23 Jul, 2016 11:23 11.15 Kb 2909
6899 hbv 2016.pdf PDF 2016 admin 23 Jul, 2016 11:22 308.30 Kb 1155
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