GAS5 rs2067079 and miR-137 rs1625579 functional SNPs and risk of chronic hepatitis B virus infection among Egyptian patients.
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ABSTRACT:
SUBMITTER: Mahmoud RH
PROVIDER: S-EPMC8501054 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND: Hepatitis G virus (HGV) is an RNA virus. It is mainly transmitted through exposure to contaminated blood although other routes may also exist. Patients with chronic renal failure (CRF) are at high risk of acquiring HGV because they require frequent blood transfusions. Ongoing HGV infection can be only diagnosed by demonstrating viremia in patient sample by reverse transcriptase (RT) PCR. Antibodies to the envelop protein E2 (anti E2) of HGV is an indicator of virus clearance and testify past HGV contact. This cross sectional study was done to assess the frequency of HGV exposure (ongoing and past infection) in Egyptian children with CRF and to study the possible risk factors of infection. METHODS: This study included 100 children with CRF [34 on regular haemodialysis (HD) and 66 before the start of dialysis (predialysis)]. All patients sera were tested for HGV RNA by RT-PCR, anti E2, hepatitis C virus (HCV) antibody, hepatitis B surface antigen (HBsAg), and hepatitis B core antibody (HBcAB). Twenty five healthy children of matched age & sex were used as controls. RESULTS: HGV RNA was positive in 9 (26.5%) of HD and 9 (13.6%) of predialysis children. Anti E2 was positive in 14 (41.2%) of HD and 19 (28.8%) of predialysis children.In comparison to controls; CRF (n = 100); HD and predialysis children had significantly higher prevalence of anti E2 [4% VS 33% for all CRF cases; (p = 0.002)& 41.2% (p = 0.002) and 28.8% (p = 0.01); for HD and predialysis groups; respectively]. HGV RNA was significantly more prevalent only in HD children in comparison to controls (p = 0.03). HD and predialysis children did not have significant difference in the prevalence of HGV RNA (p = 0.16) or anti E2 (p = 0.26).HGV exposure was not correlated with positivity of anti HCV (p = 0.32), HCV RNA (0.09), HBsAg/HBcAB (p = 1), age (p = 0.06), or gender (p = 0.83). It was significantly correlated with duration of the disease (p < 0.001). Ongoing HGV infection was significantly more prevalent with frequent blood transfusion (p < 0.001). There were no significant differences in serum levels of ALT (p = 0.09), total bilirubin (p = 0.1) and albumin (p = 0.06) in children with ongoing infection in comparison to healthy controls. CONCLUSIONS: The frequency of HGV exposure in Egyptian children with CRF appears to be high and is mainly related to frequent blood transfusions and longer disease duration. HGV infection in these children is not associated with significant changes in hepatic biochemical parameters.
| S-EPMC2804678 | biostudies-literature
Project description:Genetic variants in microRNAs (miRNAs) can alter the miRNAs expression and/or function, accordingly, affecting the related biological pathways and disease risk. Dysregulation of miR-155 and miR-146a expression levels has been well-described in viral hepatitis B (HBV). In the current study, we aimed to assess rs767649 T/A and rs57095329 A/G polymorphisms in miR-155, and miR-146a genes, respectively, as risk factors for Chronic HBV (CHBV) in the Egyptian population. Also, we aimed to do in silico analysis to investigate the molecules that primarily target these miRNAs. One hundred patients diagnosed as CHBV and one hundred age and sex-matched controls with evidence of past HBV infection were genotyped for miR-155 (rs767649) and miR-146a (rs57095329) using real-time polymerase chain reaction. The rs767649 AT and AA genotypes in CHBV patients confer four folds and ten folds risk respectively, as compared to control subjects [(AOR = 4.245 (95%CI 2.009-8.970), p<0.0001) and AOR = 10.583 (95%CI 4.012-27.919), p<0.0001, respectively)]. The rs767649 A allele was associated with an increased risk of developing CHBV (AOR = 2.777 (95%CI 1.847-4.175), p<0.0001). There was a significant difference in the frequency of rs57095329 AG and GG genotypes in CHBV patients compared to controls. AG and GG genotypes showed an increase in the risk of developing CHBV by about three and six folds respectively [AOR = 2.610 (95%CI 1.362-5.000), p = 0.004] and [AOR = 5.604 (95%CI 2.157-14.563), p<0.0001].We concluded that rs57095329 and rs767649 SNPs can act as potential risk factors for the development of CHBV in the Egyptian population.
| S-EPMC8389509 | biostudies-literature
Project description:During hepatitis C virus (HCV) chronic infection, extrahepatic manifestations are frequent and polymorphous. This article reports on a large cohort of patients with HCV-related autoimmune or lymphoproliferative disorders, from mixed cryoglobulinemia vasculitis to frank lymphomas. The relationship between HCV infection and such immune-related diseases has been formally demonstrated by epidemiological, clinical, immunological and pathological data, and results of therapeutic trials. More recently, other nonliver-related HCV disorders have been reported, including cardiovascular (i.e. stroke, ischemic heart disease), renal, metabolic and central nervous system diseases. For these manifestations, most evidence comes from large epidemiological studies; there is a need for mechanistic studies and therapeutic trials for confirmation. Beyond the risk of developing liver complications, that is, cirrhosis and liver cancer, patients with HCV infection have an increased risk of morbidity and mortality related to nonliver diseases. HCV chronic infection should be analyzed as a systemic disease in which extrahepatic consequences increase the weight of its pathological burden. The need for effective viral eradication measures is underlined.
| S-EPMC4735500 | biostudies-other
Project description:Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are the most common causes of chronic liver diseases and hepatocelluar carcinomas. Over the past few years, the liver-enriched microRNA-122 (miR-122) has been shown to differentially regulate viral replication of HBV and HCV. It is notable that the level of miR-122 is positively and negatively regulated by HCV and HBV, respectively. Consistent with the well-documented phenomenon that miR-122 promotes HCV accumulation, inhibition of miR-122 has been shown as an effective therapy for the treatment of HCV infection in both chimpanzees and humans. On the other hand, miR-122 is also known to block HBV replication, and HBV has recently been shown to inhibit miR-122 expression; such a reciprocal inhibition between miR-122 and HBV suggests an intriguing possibility that miR-122 replacement may represent a potential therapy for treatment of HBV infection. As HBV and HCV have shared transmission routes, dual infection is not an uncommon scenario, which is associated with more advanced liver disease than either HBV or HCV mono-infection. Thus, there is a clear need to further understand the interaction between HBV and HCV and to delineate the role of miR-122 in HBV/HCV dual infection in order to devise effective therapy. This review summarizes the current understanding of HBV/HCV dual infection, focusing on the pathobiological role and therapeutic potential of miR-122.
| S-EPMC4381172 | biostudies-literature
Project description:Chronic HCV infection, a highly endemic disease in Egypt, is usually asymptomatic for decades after infection. Prediction questionnaire tool was proofed to be a valuable, feasible and efficient instrument for the screening of several diseases. We previously developed an Egyptian HCV risk screening tool (EGCRISC). This study aims to validate/modify EGCRISC. A cross-sectional study testing 4579 individuals by EGCRISC as well as ELISA/PCR was performed. The sample was a stratified cluster sampling from urban and rural areas in Upper and Lower Egypt using a proportional allocation technique. The degree of agreement and positive and negative posttest probabilities were calculated. ROC curve was done and the cutoff points were customized for best performance. The total score was further classified into three levels according to the risk load. The mean age of the participants was 41.1±12.2 in whom HCV prevalence was 8.6%. EGCRISC, particularly after modifying the cutoff points, has a good discriminating ability. The degree of agreement was at least 68.1% and the positive posttest probability ranged from 5% to 37.2% whereas the negative posttest probability was in the range 1% to 17%. We conclude that EGCRISC is a valid tool that can potentially screen for HCV infection risk in Egypt and could diminish the demand for mass serologic screening in those apparently at minimal risk. Extensive use of electronic and self- or interviewer-administered risk-based screening strategy may simplify and promote overall screening and detection of HCV dissimilar communities.
| S-EPMC5176306 | biostudies-other
Project description:Worldwide, more than one million people die each year from hepatitis C virus (HCV) related diseases, and over 300 million people are chronically infected with hepatitis B or C. Egypt used to be on the top of the countries with heavy HCV burden. Some countries are making advances in elimination of HCV, yet multiple factors preventing progress; remain for the majority. These factors include lack of global funding sources for treatment, late diagnosis, poor data, and inadequate screening. Treatment of HCV in Egypt has become one of the top national priorities since 2007. Egypt started a national treatment program intending to provide cure for Egyptian HCV-infected patients. Mass HCV treatment program had started using Pegylated interferon and ribavirin between 2007 and 2014. Yet, with the development of highly-effective direct acting antivirals (DAAs) for HCV, elimination of viral hepatitis has become a real possibility. The Egyptian National Committee for the Control of Viral Hepatitis did its best to provide Egyptian HCV patients with DAAs. Egypt adopted a strategy that represents a model of care that could help other countries with high HCV prevalence rate in their battle against HCV. This review covers the effects of HCV management in Egyptian real life settings and the outcome of different treatment protocols. Also, it deals with the current and future strategies for HCV prevention and screening as well as the challenges facing HCV elimination and the prospect of future eradication of HCV.
| S-EPMC6189850 | biostudies-other
Project description:Background & aimsHepatitis delta virus (HDV) infection is the most severe form of viral hepatitis. Although HDV-associated liver disease is considered immune-mediated, adaptive immune responses against HDV are weak. Thus, the role of several other cell-mediated mechanisms such as those driven by mucosa-associated invariant T (MAIT) cells, a group of innate-like T cells highly enriched in the human liver, has not been extensively studied in clinical HDV infection.MethodsMAIT cells from a sizeable cohort of patients with chronic HDV were analyzed ex vivo and in vitro after stimulation. Results were compared with MAIT cells from hepatitis B virus (HBV) monoinfected patients and healthy controls.ResultsCirculating MAIT cells were dramatically decreased in the peripheral blood of HDV-infected patients. Signs of decline were also observed in the liver. In contrast, only a modest decrease of circulating MAIT cells was noted in HBV monoinfection. Unsupervised high-dimensional analysis of residual circulating MAIT cells in chronic HDV infection revealed the appearance of a compound phenotype of CD38hiPD-1hiCD28loCD127loPLZFloEomesloHelioslo cells indicative of activation. Corroborating these results, MAIT cells exhibited a functionally impaired responsiveness. In parallel to MAIT cell loss, HDV-infected patients exhibited signs of monocyte activation and increased levels of proinflammatory cytokines IL-12 and IL-18. In vitro, IL-12 and IL-18 induced an activated MAIT cell phenotype similar to the one observed ex vivo in HDV-infected patients. These cytokines also promoted MAIT cell death, suggesting that they may contribute to MAIT cell activation and subsequent loss during HDV infection.ConclusionsThese results suggest that chronic HDV infection engages the MAIT cell compartment causing activation, functional impairment, and subsequent progressive loss of MAIT cells as the HDV-associated liver disease progresses.Lay summaryHepatitis delta virus (HDV) infection is the most severe form of viral hepatitis. We found that in patients with HDV, a subset of innate-like T cells called mucosa-associated invariant T cells (or MAIT cells), which are normally abundant in peripheral blood and the liver, are activated, functionally impaired and severely depleted.
| S-EPMC6642010 | biostudies-literature
Project description:The human hepatitis B virus (HBV) is a small-enveloped DNA virus causing acute and chronic hepatitis. Despite the existence of an effective prophylactic vaccine and the strong capacity of approved antiviral drugs to suppress viral replication, chronic HBV infection (CHB) continues to be a major health burden worldwide. Both the inability of the immune system to resolve CHB and the unique replication strategy employed by HBV, which forms a stable viral covalently closed circular DNA (cccDNA) minichromosome in the hepatocyte nucleus, enable infection persistence. Knowledge of the complex network of interactions that HBV engages with its host is still limited but accumulating evidence indicates that epigenetic modifications occurring both on the cccDNA and on the host genome in the course of infection are essential to modulate viral activity and likely contribute to pathogenesis and cancer development. Thus, a deeper understanding of epigenetic regulatory processes may open new venues to control and eventually cure CHB. This review summarizes major findings in HBV epigenetic research, focusing on the epigenetic mechanisms regulating cccDNA activity and the modifications determined in infected host cells and tumor liver tissues.
| S-EPMC7174266 | biostudies-literature
Project description:To clarify the prevalence of occult hepatitis B virus (HBV) infection (OBI) and the association between OBI and liver disease progression, defined as development of liver cirrhosis or hepatocellular carcinoma (HCC), worsening of Child-Pugh class, or mortality in cases of chronic hepatitis C virus (HCV) infection.This prospective cohort study enrolled 174 patients with chronic HCV infection (chronic hepatitis, n = 83; cirrhosis, n = 47; HCC, n = 44), and evaluated disease progression during a mean follow-up of 38.7 mo. OBI was defined as HBV DNA positivity in 2 or more different viral genomic regions by nested polymerase chain reaction using 4 sets of primers in the S, C, P and X open reading frame of the HBV genome.The overall OBI prevalence in chronic HCV patients at enrollment was 18.4%, with 16.9%, 25.5% and 13.6% in the chronic hepatitis C, liver cirrhosis and HCC groups, respectively (P = 0.845). During follow-up, 52 patients showed disease progression, which was independently associated with aspartate aminotransferase > 40 IU/L, Child-Pugh score and sustained virologic response (SVR), but not with OBI positivity. In 136 patients who were not in the SVR state during the study period, OBI positivity was associated with neither disease progression, nor HCC development.The prevalence of OBI in chronic HCV patients was 18.4%, and OBI was not associated with disease progression in South Koreans.
| S-EPMC5107707 | biostudies-literature
Project description:BACKGROUND:Previous reports show conflicting results regarding hepatitis B virus (HBV) vaccine efficacy in Hepatitis C virus (HCV)-infected individuals. AIMS:To evaluate HBV-vaccine response and identify possible factors that may contribute to lower vaccine efficacy in patients infected with HCV. METHODS:We retrospectively evaluated all patients with chronic HCV infection at Hennepin County Medical Center, in Minneapolis, Minnesota, between 2002 and 2018. We addressed laboratory, liver-related, virus-related as well as vaccine-related variables, and their association to HBV vaccine response. Differences were tested using either a Chi-squared test or a T test to compare means between the two populations. Multivariate regression was modeled as a logistic regression. RESULTS:1506 patients were evaluated, of which 525 received appropriate HBV vaccination and were assessed for response. Among those, 79% were vaccine responders and 21% were non-responders. On multivariate analysis, cirrhosis was associated with lower response to the vaccine (OR 0.6, CI 0.44-0.94). We found no significant differences for vaccine response in relation to smoking (87% vs 86%), IV drug abuse (74% vs 72%), Diabetes Mellitus (26% vs 22%) being on hemodialysis (2% vs.5%), or virus related variables. CONCLUSION:HCV infection seems to impair HBV vaccine response, with cirrhosis being the only identifiable risk factor for hypo-responsiveness among studied clinical and virus-related variables.
| S-EPMC7449383 | biostudies-literature