An Integrative Gene Expression Microarray Meta-analysis Identifies Host Factors and Key Signatures Involved in Hepatitis B Virus Infection

2020 ◽  
Vol 20 (5) ◽  
pp. 698-707 ◽  
Author(s):  
Mohcine Elmessaoudi-Idrissi ◽  
Marc P. Windisch ◽  
Anass Kettani ◽  
Haya Altawalah ◽  
Pascal Pineau ◽  
...  

: >Hepatitis B virus (HBV) is a global health concern. Viral and host factors orchestrate the natural history of HBV infection, but the impact of host factors that influence the clinical course of the disease remains poorly understood. The aim of this study was to identify host factors crucial to the HBV life cycle by conducting a meta-analysis utilizing public microarray datasets. Methods: An integrative meta-analysis of expression data from two microarray datasets of HBVinfected liver tissues and healthy uninfected livers was conducted to identify gene expression signatures and overlapping biological processes modulating infection/disease. Results: Using integrative meta-analysis of expression data (INMEX), we identified across two datasets a total of 841 genes differentially expressed during HBV infection, including 473 upregulated and 368 downregulated genes. In addition, through functional enrichment and pathway analysis, we observed that Jak-STAT, TLR, and NF-κB are the most relevant signaling pathways in chronic HBV infection. The network-based meta-analysis identified NEDD8, SKP2, JUN, and HIF1A as the most highly ranked hub genes. Conclusion: Thus, these results may provide valuable information about novel potential host factors modulating chronic HBV infection. Such factors may serve as potential targets for the development of novel therapeutics such as activin receptor-like kinase inhibitors.

2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Han Shi ◽  
Hongyan He ◽  
Suvash Chandra Ojha ◽  
Changfeng Sun ◽  
Juan Fu ◽  
...  

Abstract Background: It has been reported that polymorphisms of signal transducer and activator of transcription (STAT) 3 and STAT4 might be associated with susceptibility to hepatitis B virus (HBV) infection and risk of chronic hepatocellular carcinoma (HCC). Owing to limitation of sample size and inconclusive results, we conducted a meta-analysis to clarify the association. Methods: We identified relevant studies by a systematic search of Medline/PubMed, Embase, Web of Science and the Cochrane Library up to 20 February 2019. The strength of the association measured by odds ratios (OR) with 95% confidence intervals (CIs) was studied. All the statistical analyses were conducted based on Review Manager 5.3 software. Results: A total of 5242 cases and 2717 controls from five studies were included for the STAT3 polymorphism, 5902 cases and 7867 controls from nine studies for the STAT4 polymorphism. Our results suggested that STAT3 rs1053004 polymorphism was a significant risk factor of chronic HBV infection (C vs. T: OR = 1.17, 95% CI: 1.07–1.29, PA=0.0007; CC + CT vs. TT: OR = 1.38, 95% CI: 1.09–1.76, PA=0.008). Validation with all the genetic models revealed that rs7574865 polymorphism of STAT4 gene was closely associated with chronic HBV infection (PA<0.01) and chronic hepatitis B (CHB)-related HCC (PA<0.05). Meanwhile, the authenticity of the above meta-analysis results was confirmed by trial sequential analysis (TSA). Conclusions: The meta-analysis showed that STAT3 rs1053004 polymorphism may be the risk for developing chronic HBV infection but not associated with HCC. The present study also indicates that STAT4 rs7574865 polymorphism increased the risk of chronic HBV infection and HCC.


Virology ◽  
1990 ◽  
Vol 174 (1) ◽  
pp. 299-304 ◽  
Author(s):  
Massimo Levrero ◽  
O. Jean-Jean ◽  
C. Balsano ◽  
H. Will ◽  
M. Perricaudet

2017 ◽  
Vol 45 (8) ◽  
Author(s):  
Ai-Min Cui ◽  
Jian-Guo Shao ◽  
Hai-Bo Li ◽  
Yi Shen ◽  
Zhi-Xian Chen ◽  
...  

AbstractObjectives:To assess the association of chronic hepatitis B virus (HBV) infection with preterm birth (PTB).Methods:A cohort of 20,498 pregnant women (497 HBV carriers with 20,001 non-HBV controls) with normal alanine aminotransferase (ALT) levels was selected from the Obstetrics & Gynecology Hospital of Nantong University. The clinical parameters and PTB incidence were compared between HBV carriers and non-HBV subjects. For the meta-analysis, we searched the PubMed, Ovid and Cochrane Library databases for studies comparing PTB incidence between individuals with chronic HBV infection and non-HBV subjects.Results:HBV carriers were slightly older and had slightly higher ALT levels within normal limits. The body mass index, education and history of pregnancy between HBV carrier and non-HBV groups were comparable. PTB incidence was not associated with HBV carrier status [relative risk (RR) 0.98, 95% confidence interval (CI) 0.71–1.37] in our cohort. However, the meta-analysis involving eight published studies and our study revealed a significant association between chronic HBV infection and PTB incidence (pooled RR 1.26, 95% CI 1.19–1.33).Conclusion:While maternal HBV carriers did not have a higher incidence of PTB in our cohort, the meta-analysis indicates that individuals with chronic HBV infection appeared to be at risk of PTB as a whole.


2021 ◽  
Vol 10 (13) ◽  
pp. 2926
Author(s):  
Sirinart Sirilert ◽  
Theera Tongsong

This review aimed to provide an update on the impact of pregnancy on the natural course of hepatitis B virus (HBV) infection and also on the impact of HBV infection on adverse pregnancy outcomes, including mother-to-child transmission (MTCT). For the literature review, original research articles, review articles, and guidelines were narratively reviewed and comprehensively validated. The databases of PubMed, EMBASE, and CINAHL were carefully searched for articles in English on topics related to HBV infection, pregnancy, and vertical transmission from 1960 to May 2021. Immunological changes during pregnancy such as suppression of Th1 response and induction of Th2 immunity lead to an impaired immune reaction to HBV and stimulate viral activity along with the reduction of CD8 T cells to escape immune detection. The impact of pregnancy on the natural course of chronic HBV infection seems to be minimal, while pregnancy can increase morbidity and mortality in the case of advanced HBV hepatitis or cirrhosis. Importantly, hepatitis flare or alanine aminotransferase (ALT) flare can occur during pregnancy and is more common during the postpartum period due to the interaction between HBV and the immune response. Interestingly, the impact of HBV infection on adverse pregnancy outcomes is more serious than ever thought. Updated evidence indicates that pregnancies with chronic HBV infection increase the risk of preterm birth and gestational diabetes, especially in cases of positive hepatitis e antigen (HBeAg).


2009 ◽  
Vol 199 (11) ◽  
pp. 1599-1607 ◽  
Author(s):  
Chiemi Noguchi ◽  
Michio Imamura ◽  
Masataka Tsuge ◽  
Nobuhiko Hiraga ◽  
Nami Mori ◽  
...  

1994 ◽  
pp. 168-172
Author(s):  
Geert Leroux-Roels ◽  
Els Van Hecke ◽  
Jozef Paradijs ◽  
Chantal Molitor ◽  
Carine Bastin ◽  
...  

Virology ◽  
1993 ◽  
Vol 196 (1) ◽  
pp. 138-145 ◽  
Author(s):  
Masahiro Takayanagi ◽  
Shinichi Kakumu ◽  
Tetsuya Ishikawa ◽  
Yasuyuki Higashi ◽  
Kentaro Yoshioka ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Steffen B. Wiegand ◽  
Bastian Beggel ◽  
Anika Wranke ◽  
Elmira Aliabadi ◽  
Jerzy Jaroszewicz ◽  
...  

Abstract Chronic hepatitis B virus (HBV) infection may follow four different consecutive phases, which are defined by virology as well as biochemical markers and differ in terms of prognosis and need for antiviral treatment. Currently, host responses reflected by immune markers are not considered in this definition. We aimed to study soluble immune markers and their distribution in different phases of chronic HBV infection. In this cross-sectional retrospective study, we investigated a panel of 14 soluble immune markers (SIM) including CXCL10 in 333 patients with chronic HBV infection. In a small cohort of HBeAg positive patients we analyzed SIM before and after HBeAg seroconversion and compared seroconverters to patients with unknown outcome. Significant differences were documented in the levels of several SIM between the four phases of chronic HBV infection. The most pronounced difference among all investigated SIM was observed for CXCL10 concentrations with highest levels in patients with hepatitis. TGF-β and IL-17 revealed different levels between HBeAg negative patients. HBeAg positive patients with HBeAg seroconversion presented higher amounts of IL-12 before seroconversion compared to HBeAg positive patients with unknown follow up. SIM such as CXCL10 but also IL-12, TGF-β and IL-17 may be useful markers to further characterize the phase of chronic HBV infection.


BMJ Open ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. e027696 ◽  
Author(s):  
Jiahui Si ◽  
Canqing Yu ◽  
Yu Guo ◽  
Zheng Bian ◽  
Ruogu Meng ◽  
...  

ObjectivesChronic hepatitis B virus (HBV) infection is associated with a higher risk of liver diseases. Substantial uncertainty remains, however, about the associations of HBV infection with mortality from extrahepatic causes, especially from subtypes of cardiovascular diseases. We prospectively examined the association of chronic HBV infection with total and cause-specific mortality.DesignPopulation-based prospective cohort study.SettingChina Kadoorie Biobank in which participants from 10 geographically diverse areas across China were enrolled between 2004 and 2008.Participants475 801 participants 30–79 years of age without reporting major chronic diseases at baseline were enrolled. Hepatitis B surface antigen (HBsAg) was tested using an on-site rapid test strip at baseline.Primary and secondary outcome measuresTotal and cause-specific mortality.ResultsA total of 35 822 deaths were recorded during ~10 years of follow-up. In multivariable-adjusted analyses, compared with HBsAg-negative participants, HBsAg-positive participants had an increased risk of total mortality (HR=2.01, 95% CI: 1.91 to 2.12), which was higher in men (HR=2.16, 95% CI: 2.01 to 2.31) than in women (HR=1.74, 95% CI: 1.60 to 1.90). Presence of HBsAg was associated with increased mortality from liver cancer (1339 deaths, HR=13.95, 95% CI: 12.46 to 15.62), infections (410 deaths, HR=10.30, 95% CI: 8.21 to 12.94), digestive diseases (688 deaths, HR=6.83, 95% CI: 5.49 to 8.50), intracerebral haemorrhage (4077 deaths, HR=1.38, 95% CI: 1.14 to 1.68) and ischaemic heart diseases (4624 deaths, HR=1.31, 95% CI: 1.09 to 1.58). The positive association between HBsAg status and risk of death was stronger in participants younger than 50 years, smokers, physically active or non-hypertensive participants.ConclusionsAmong Chinese adults, chronic HBV infection was associated with increased mortality from a range of hepatic and extrahepatic diseases.


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