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Background: There is limited data regarding the use of emergency departments (EDs) for infectious disease screening and vaccination in resource-limited regions. In these settings, EDs are often the only contact that patients have with the healthcare system, turning an ED visit into an opportune time to deliver preventative health services.Methods: In this pilot study, patients that met inclusion criteria were prospectively tested for hepatitis B surface antigen test (HBsAg). Previously unvaccinated patients who tested negative for HBsAg were offered HBV vaccination. The study setting was a public infectious disease hospital in Cordoba, Argentina. The primary outcomes were new HBV diagnoses, as well as vaccination completion between screening modalities (Point-of-Care-Testing-POCT vs. laboratory testing) and same vs. different day vaccination.Results: We screened 100 patients for HBV (75 POCT & 25 laboratory). The median age of participants was 35 years (IQR 24-52) and 55% were male. No patients tested positive for HBsAg. All patients who completed first dose vaccination were initially screened with the POCT. No patients screened with laboratory testing returned for vaccination. Patients who were scheduled for vaccination the same day were more likely to complete vaccination compared to those scheduled for another day (75% vs. 14%, p < .001).Conclusion: Our study supports the use of HBV POCTs in the ED in conjunction with vaccination of HBV-negative individuals. In regions with low HBV endemicity, direct vaccination without HBsAg testing may be more cost effective. We believe that this acute-care screening model is applicable to other resource-limited settings. [ABSTRACT FROM AUTHOR]

• Description of autochthonous cholestatic hepatitis E in Europe. • Bimodal development of acute hepatitis with negative virus in blood. • Found dissociation of peripheral immune responses during intrahepatic hepatitis E virus replication following negativization in blood. We report the immune response during a case of acute HEV response in a patient with an acute hepatitis E virus (HEV) genotype 3 infection in the Netherlands. Cytokine evaluation was performed via multiplex cytokine array for 65 immune markers in plasma during the different phases of hepatitis. The patient initially presented with features typical of acute viral hepatitis, with detectable HEV RNA in blood. This evolved into a cholestatic disease following peripheral clearance of the virus, leading to the demise of the patient. Real time PCR revealed the presence of HEV in liver tissue, suggestive of active intrahepatic infection despite clearance in blood. During the phase of detectable HEV RNA in serum, there was a surge in T-cell-related immune mediators, as well as interferon alpha and interferon gamma-induced protein 10 (IP-10), characteristic of a viral infection. After clearance of the virus in the blood and development of cholestatic hepatitis, several inflammatory markers subsided, followed by an increase in immune factors related to anti-inflammatory activity, as well as monocyte/macrophage-related markers, likely due to the intrahepatic presence of the virus. This report describes the dissociation of intra- and extra-hepatic immune responses during acute HEV infection. As shedding of the virus became solely intrahepatic, an immune profile reflective of the activity of hepatic resident cells was observed. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is a RNA virus that can cause hepatitis. In immunocompetent individuals, infection with HEV usually leads to asymptomatic seroconversion. However, in immunosuppressed patients, such as transplant recipients, HEV can develop into a chronic infection. Studies regarding the seroprevalence and clinical implications of HEV in patients infected with the human immunodeficiency virus (HIV) are conflicting. Levels of CD4 count in blood seem to be the most widely associated risk factor, while other factors such as meat consumption or proximity to animals are less clearly associated with HEV infection. Progression to chronicity, as well as extrahepatic manifestations of HEV seem rare in HIV, and the implications of HEV in liver disease progression are poorly understood in the HIV-infected. In this review we describe the epidemiology, risk factors, and clinical implications of HEV infection in individuals infected with HIV. [ABSTRACT FROM AUTHOR]

Several reports suggest that the glutathione-S-transferase (GST) family of enzymes is involved in a variety of cancers, due to their carcinogen-detoxification properties. A polymorphism in codon 105 of the pi variant (GSTP1 I105V), which affects the enzymatic activity of the enzyme, has been linked to the incidence of cancers from different organs. However, the published data in prostate cancer (PCa) is controversial. Some studies report an association with the GSTP1 I105V polymorphism and sporadic PCa, whereas other studies report no association. Recently, one study showed a positive correlation between the GSTP1 I105V polymorphism and familial PCa in a Japanese population. In the present study, we assessed the correlation of the GSTP1 I105V polymorphism with familial and sporadic PCa in an American population. We analyzed DNA samples from 438 patients with familial PCa, 499 patients with sporadic PCa, and 510 controls. We found no significant association between the GSTP1 I105V polymorphism and familial or sporadic PCa when compared to the control group [odds ratio (OR) =1.0 (0.74–1.37); P=0.58]. Moreover, no association was found after stratification for age of diagnosis, Gleason grade, or lymph node involvement [OR =0.84 (0.65–1.09), P=0.37]. These data indicate that there is no associated risk for sporadic or familial PCa in American families containing the GSTP1 I105V polymorphism. [Copyright &y& Elsevier]

Prostate cancer (PCa) is the leading diagnosed malignancy in men in western countries. The relationship between androgens and the androgen receptor (AR) has been studied extensively in PCa. Plasma levels of androgens show variations between different populations, and in many cases this correlates with PCa susceptibility. Indeed, exposure of the fetus to higher androgen concentrations appears to be a risk factor for PCa. The AR is present in the majority of PCa, and its activation by androgens leads to different proliferative, apoptotic and angiogenic events. These events are in turn mediated by dysregulation of cyclin-dependent kinases, apoptotic factors and even mutations in the AR. Although androgen ablation has been the mainstay non-surgical treatment for this disease, most tumors will eventually become refractory to treatment. Different cellular mechanisms appear to be involved in the androgen-independent progression of PCa, including cytokine and growth factor-mediated activation of the AR as well as neuroendocrine differentiation. Thus, an understanding of the cellular mechanisms involved in androgen action may lead to better therapeutic targets for PCa. [Copyright &y& Elsevier]

Concern has arisen about the development of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) infection treated with direct-acting antivirals (DAAs). To identify patients at risk for HCC, we evaluated serum levels of immune mediators before, during, and after DAA treatment of HCV infection. Our study included 13 patients who developed HCC within 18 months after treatment (3 with HCC recurrence and 10 with new HCC) and 10 patients who did not develop HCC (controls), within at least 24 months of treatment (median, 26 months). We identified a set of 12 immune mediators (cytokines, growth factors, and apoptosis markers) whose levels were significantly higher in serum before DAA treatment of patients who eventually developed de novo HCC compared with controls. A panel of 9 cytokines, measured in serum before treatment (MIG, IL22, TRAIL, APRIL, VEGF, IL3, TWEAK, SCF, IL21), identified patients who developed de novo HCC with an area under the receiver operating characteristic curve value higher than 0.8. Further analyses of changes in levels of inflammatory cytokines during DAA treatment also provides important information about HCV-induced carcinogenesis and the effects of DAAs. [ABSTRACT FROM AUTHOR]

Chronic HBV is clinically categorized into 4 phases by a combination of serum HBV DNA levels, HBeAg status and alanine aminotransferase (ALT): immunotolerant (IT), immune-active (IA), inactive carrier (IC) and HBeAg-negative hepatitis (ENEG). Immune and virological measurements in the blood have proven useful but are insufficient to explain the interrelation between the immune system and the virus since immune dynamics differ in the blood and liver. Furthermore, the inflammatory response in the liver and parenchymal cells cannot be fully captured in blood. Immunological composition and transcriptional profiles of core needle liver-biopsies in chronic HBV phases were compared to those of healthy controls by multiplex immunofluorescence and RNA-sequencing (n = 37 and 78, respectively) analyses. Irrespective of the phase-specific serological profiles, increased immune-gene expression and frequency was observed in chronic HBV compared to healthy livers. Greater transcriptomic deregulation was seen in IA and ENEG (172 vs. 243 DEGs) than in IT and IC (13 vs. 35 DEGs) livers. Interferon-stimulated genes, immune-activation and exhaustion genes (ICOS , CTLA4 , PDCD1) together with chemokine genes (CXCL10 , CXCL9) were significantly induced in IA and ENEG livers. Moreover, distinct immune profiles associated with ALT elevation and a more accentuated immune-exhaustion profile (CTLA4 , TOX , SLAMF6 , FOXP3) were observed in ENEG, which set it apart from the IA phase (LGALS9 , PDCD1). Interestingly, all HBV phases showed downregulation of metabolic pathways vs. healthy livers (fatty and bile acid metabolism). Finally, increased leukocyte infiltrate correlated with serum ALT, but not with HBV DNA or viral proteins. Our comprehensive multi-parametric analysis of human livers revealed distinct inflammatory profiles and pronounced differences in intrahepatic gene profiles across all chronic HBV phases in comparison to healthy liver. Immunological studies on chronic HBV remain largely restricted to assessment of peripheral responses due to the limited access to the site of infection, the liver. In this study, we comprehensively analyzed livers from a well-defined cohort of patients with chronic HBV and uninfected controls with state-of-the-art techniques, and evaluated the differences in gene expression profiles and inflammation characteristics across distinct disease phases in patients with chronic HBV. [Display omitted] • RNA-Seq and multiplex immunofluorescence (mIF) was performed on liver biopsies to characterize the HBV clinical phases. • Chronic HBV livers were characterized by higher immune-gene expression and leukocyte infiltrate than healthy livers. • ALT determined immune gene expression profiles in livers of IA and ENEG patients. • Immune-exhaustion profiles were observed in livers of IA and ENEG patients. • Leukocyte infiltrate correlated with serum ALT, but not with HBV DNA or intrahepatic HBcAg and HBsAg. [ABSTRACT FROM AUTHOR]

• RT-LAMP assay was developed for the detection of HCV in a single-closed tube. • The assay is simple, rapid, cost-effective, and result can be observed by naked eye. • The assay showed a 95.5% sensitivity and 100% specificity with no cross-reactions. • The assay could be able to detect 100% of samples with HCV genotype 6. • The assay is an alternative tool for point-of-care testing. The aim was to develop a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for the detection of hepatitis C virus (HCV) in a single closed tube. Plasma samples were collected from 200 HCV-infected patients. HCV-RNA was detected by one-step RT-LAMP processed at 65 °C for 60 min. The amplified products were detected by hydroxynaphthol blue (HNB)-dependent visual method and gel electrophoresis. Specificity was tested against other viruses. Sensitivity was determined using serial dilutions of extracted RNA. The RT-LAMP assay detected 97.5% of HCV-RNA genotype 1, 91.1% of genotype 3, and 100% of genotype 6. The color change was evidenced with the naked eye. The assay demonstrated a clinical sensitivity of 95.5% and specificity of 100%, as well as no cross-reactivity with other viruses (i.e., hepatitis B virus, HIV). The limit of detection was as low as 10 ng per reaction for HCV genotypes 1a and 6, while it was 100 ng for genotype 3a. The assay showed a 100% detection threshold at a viral load of 5.00 log 10 IU/mL in the clinical samples tested. This study demonstrated the use of an RT-LAMP assay for the detection of HCV in a simple, rapid, and cost-effective manner, which will be useful in resource-limited settings to allow the identification of individuals in need of HCV treatment. [ABSTRACT FROM AUTHOR]