Search

Background: HCV eradication with antiviral treatment reduces hepatic disease, but some patients remain at risk of progression to cirrhosis despite HCV clearance. We aimed to examine the association between peripheral blood mononuclear cells (PBMCs) gene expression before HCV therapy and a pronounced decrease in the liver stiffness measurement (LSM) value in HIV/HCV-coinfected patients after HCV treatment and achievement of sustained virological response (SVR). Methods: We performed a retrospective study in 48 HIV/HCV-coinfected patients who started anti-HCV treatment with at least advanced fibrosis (LSM ≥9.5). Total RNA was extracted from PBMCs at baseline, and poly(A) RNA sequencing was performed. The outcome was an LSM reduction greater than 50% (LSMred>50%) about 48 weeks after HCV treatment. Results: Seven patients (14.5%) reduced LSM by over 50%. We found 47 significant differentially expressed (SDE) genes associated with reaching an LSMred>50% after achieving HCV eradication, 42 upregulated and 5 downregulated in the LSMred>50% group. Ten and five of these upregulated genes were classified into two significantly enriched KEGG pathways: cell cycle and progesterone-mediated oocyte maturation (q-value <0.05), respectively. Two SDE genes achieved excellent discrimination ability: NCAPG had an AUROC of 0.908, NHLRC1 of 0.879, and a logistic regression model with these two genes of 0.955. Conclusion: A pre-treatment gene expression signature in PBMCs was associated with liver fibrosis regression (LSMred>50%) after achieving HCV clearing with HCV therapy in HIV/HCV-coinfected patients, where two SDE genes (NCAPG and NHLRC1) showed the greatest predictive capacity, which could be used as a noninvasive marker of liver fibrosis regression. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate the association of baseline coagulation proteins with hospitalization variables in COVID-19 patients admitted to ICU, as well as coagulation system changes after one-year post-discharge, taking into account gender-specific bias in the coagulation profile. Methods: We conducted a prospective longitudinal study on 49 ICU-admitted COVID-19 patients. Proteins were measured using a Luminex 200™. The association between coagulation protein levels and hospitalization variables was carried out by generalized linear models adjusted by the most relevant covariates. Results: At ICU admission, lower factor XII, antithrombin, and protein C levels were linked to the need for invasive mechanical ventilation (IMV) or its duration (p=0.028; p=0.047 and p=0.015, respectively). Likewise, lower factor XII, antithrombin, and prothrombin levels were associated with longer ICU length of stay (ICU LOS) (p=0.045; p=0.022; p=0.036, respectively). From baseline to the end of the follow-up, factor XII, antithrombin, prothrombin, and protein C levels notably increased in patients with longer ICU LOS. One-year post-discharge, differences were found for factor IX, aPTT, and INR. Gender-stratified analysis showed sustained alterations in males. Conclusions: Depleted specific coagulation factors on ICU admission are associated with increased severity in critically ill COVID-19 patients. Most coagulation alterations recover one-year post-discharge, except for factor IX, aPTT and INR, which remain reduced. [ABSTRACT FROM AUTHOR]

Background and Aims: In response to direct‐acting antivirals (DAAs) therapy, patients who experience a decrease in hepatic venous pressure gradient (HVPG) considerably reduce liver complications and have increased survival. This study aimed to assess the metabolomic changes associated with the changes in HVPG from the start of DAA therapy until 48 weeks after effective DAA therapy in patients with advanced HCV‐related cirrhosis. Methods: We carried out a multicenter longitudinal study in 31 patients with advanced hepatitis C virus (HCV)‐related cirrhosis. We performed a non‐targeted metabolomic analysis using gas chromatography–mass spectrometry and liquid chromatography‐mass spectrometry, as well as analysis of inflammation‐related biomarkers using Luminex technology. The statistical analysis was performed by Generalised Linear Mixed‐effects Models (GLMM), correcting for multiple testing. Results: We found that increases of 2,3‐butanediol (AMR = 1.15; q‐value = 0.023) and taurocholic acid (AMR = 1.06; q‐value < 0.001) were significantly associated with increases in HVPG and inflammatory biomarker levels from before DAA therapy to one year after completion of successful HCV treatment. Conclusions: These metabolites have a potential role as indicators of portal hypertension evolution. [ABSTRACT FROM AUTHOR]

Various immune checkpoint proteins have been linked to cirrhosis. This study aimed to explore the association between plasma levels of these proteins measured one year after successful HCV treatment and persistently liver stiffness (defined as liver stiffness measurement (LSM) ≥ 12.5 kPa) five years after HCV treatment in people with HIV (PWH). We conducted a retrospective study involving 39 patients with HIV/HCV-coinfection who had advanced fibrosis or cirrhosis and achieved sustained virologic response (SVR). Plasma samples were obtained one year after treatment, and levels of immune checkpoints along with inflammatory biomarkers were evaluated using a Luminex 200TM analyzer. Statistical analyses were performed using Generalized Linear Models (GLMs) with a gamma distribution. Spearman correlation tests were used to analyze the correlation between significant immune checkpoints and inflammatory biomarkers. Although LSM values showed a decreasing trend over the years following successful HCV treatment, this trend was not statistically significant due to substantial variability among PWH. Persistently high liver stiffness was observed in 61.5% of patients five years after HCV treatment. Elevated plasma levels of soluble BTLA, PD-1, and TIM-3 one year after HCV treatment were associated with persistently liver stiffness five years later. These significant immune checkpoints were found to correlate with inflammatory biomarkers in PWH with persistently high liver stiffness. In conclusion, increased plasma concentrations of immune checkpoints one year after successful HCV therapy were linked to persistently high liver stiffness five years later, particularly BTLA, PD-1, and TIM-3. This suggests a potential immunopathological mechanism in ongoing liver stiffness post-HCV eradication. [ABSTRACT FROM AUTHOR]

Background: Understanding the predictors of metabolic disorders in persons with HIV/HCV coinfection post-HCV therapy is crucial for improving patient outcomes. Since immune checkpoint proteins are usually upregulated in these persons with HIV/HCV coinfection, we aimed to evaluate the association between plasma immune checkpoint proteins at baseline (before HCV therapy) and metabolic disturbances during the follow-up (about 5 years after successful HCV treatment) in persons with HIV/HCV coinfection. Methods: We performed a retrospective study on 80 persons with HIV/HCV coinfection with advanced fibrosis or cirrhosis who cleared HCV infection after successful HCV therapy and were followed for about 5 years after completion of HCV treatment. Plasma samples were collected at baseline. Immune checkpoint proteins were analyzed using a Luminex 200™ analyzer. Outcomes were the development of a metabolic event (type 2 diabetes mellitus and/or dyslipidemia) and the change in Triglycerides and glucose (TyG) index. Results: During follow-up, 21 (26%) patients developed metabolic events (type 2 diabetes mellitus/dyslipidemia), and 29 (46.0%) patients had an increase in TyG during the follow-up. Low baseline values of BTLA and LAG-3, two immune checkpoint proteins, were associated with the development of metabolic events (aAMR = 0.69 and aAMR = 0.71, respectively) and with increases in TyG values (aAMR = 0.72 and aAMR = 0.70, respectively). In addition, other immune checkpoint proteins were also inversely associated with increases in TyG. Conclusion: We discovered that low plasma levels of BTLA and LAG-3 before HCV therapy significantly correlate with an increased risk of developing metabolic disorders after treatment. [ABSTRACT FROM AUTHOR]

The pathology of respiratory syncytial virus (RSV) infection remains unclear. An unbalanced immune response to RSV infection can lead to immunopathology, causing airway damage and impaired exchange of oxygen and carbon dioxide between the air and the bloodstream. We aimed to evaluate the association of the expression of inflammatory and antiviral genes in peripheral blood with severe hypoxemia in children with RSV infection seen in the hospital emergency room. We conducted a cross-sectional study on 121 RSV-infected children seen in hospital emergency rooms between 2015 and 2023. Total RNA was extracted from whole blood samples, and gene expression (IL-6, TNFa, CXCL8, ISG15, IFIT1, RIGI, IFNb, CCL5, and CXCL10) was quantified using quantitative RT-PCR. The outcome variable was having severe hypoxemia (SpO2 ≤ 90%). The association analysis was performed using a volcano plot, adjusted logistic regression, and orthogonal partial least squares discriminant analysis (OPLSDA). We found that 26 of 121 children had severe hypoxemia (SpO2 ≤ 90%). CXCL8 was overexpressed [fold changes (FC) > 2; q-value < 0.05], and ISG15, IFIT1, RIGI, IFNb, CCL5, and CXCL10 were underexpressed (FC <0.5; q-value <0.05) in children with severe hypoxemia. These associations were ratified using adjusted logistic regression. The OPLS-DA showed that the gene expressions of CXCL8, ISG15, IFIT1, RIGI, and CXCL10 had values of variable importance in projection (VIP) ≥1, being the most relevant features. In conclusion, an imbalance favoring inflammation over antiviral defense may contribute to the pathogenesis of severe hypoxemia in RSV-infected children. These findings provide valuable insights into the pathology of RSV infection. [ABSTRACT FROM AUTHOR]

Background Extracellular vesicles (EVs), containing microRNAs (miRNAs) and other molecules, play a central role in intercellular communication, especially in viral infections caused by SARS-CoV-2. This study explores the miRNA profiles in plasma-derived EVs from patients with severe COVID-19 vs controls, identifying potential mortality predictors. Methods This prospective study included 36 patients with severe COVID-19 and 33 controls without COVID-19. EV-derived miRNAs were sequenced, and bioinformatics and differential expression analysis between groups were performed. The plasma miRNA profile of an additional cohort of patients with severe COVID-19 (n = 32) and controls (n = 12) was used to compare with our data. Survival analysis identified potential mortality predictors among the significantly differentially expressed (SDE) miRNAs in EVs. Results Patients with severe COVID-19 showed 50 SDE miRNAs in plasma-derived EVs. These miRNAs were associated with pathways related to inflammation and cell adhesion. Fifteen of these plasma-derived EV miRNAs were SDE in the plasma of severe cases vs controls. Two miRNAs, hsa-miR-1469 and hsa-miR-6124, were identified as strong mortality predictors with an area under the receiver operating characteristic curve of 0.938. Conclusions This research provides insights into the role of miRNAs within EVs in severe COVID-19 and their potential as clinical biomarkers for mortality. [ABSTRACT FROM AUTHOR]

Dried blood spot (DBS) sampling is increasingly used for hepatitis C virus (HCV) screening. HCVcAg testing offers a faster and more streamlined approach to diagnosing HCV infection. We conducted a systematic review and meta‐analysis to assess the diagnostic performance of the Abbott ARCHITECT HCV Ag assay for screening active HCV infection using DBS samples. Eight studies (n = 1229) were selected among all published studies available up to October 4, 2024, in different databases with a search strategy registered (PROSPERO: CRD42022363975). The gold standard method was the HCV PCR test. Data were analyzed using the MIDAS module in STATA with a random effects model. Combined diagnostic accuracy measures were as follows: sensitivity 85%, specificity 100%, positive likelihood ratio (PLR) 233.1, negative likelihood ratio (NLR) 0.15, and summary receiver operating characteristic (SROC) 0.99. Likelihood ratios and Fagan's nomogram suggested that the HCVcAg assay with DBS samples can confirm or rule out active HCV infection with over 92% accuracy in high‐prevalence settings (≥5%). However, in low‐prevalence settings (≤1%), a confirmatory test must be required for positive results. The ability of the test to identify people without HCV infection was high regardless of HCV prevalence, with an error rate of less than 3%. This meta‐analysis is subject to limitations, particularly due to the number of included studies and significant heterogeneity among them. HCV screening using the Abbott ARCHITECT HCV Ag assay with DBS samples showed excellent diagnostic performance, but its external validity may be limited when HCV prevalence is low (≤1%). [ABSTRACT FROM AUTHOR]

1 | INTRODUCTION HIV-controllers are a small group of subjects ( On the other hand, HIV-controllers as a whole seem to have a higher capacity to spontaneously clear hepatitis C [...], Introduction: HIV-controllers have the ability to spontaneously maintain viraemia at low or undetectable levels in the absence of antiretroviral treatment. Furthermore, HIV-controllers seem to have a superior capacity to spontaneously clear hepatitis C virus (HCV) compared to non HIV-controllers. Some of these subjects eventually lose HIV-controller status (transient controllers), whereas some HIV-controllers show a persistent natural HIV control (persistent controllers). We aimed to analyse whether persistent controllers have superior capacity to spontaneously clear HCV compared to transient controllers. Methods: We recruited HIV-controllers from January 1981 up to October 2016 with available antibodies to HCV (anti-HCV) data (n = 744). Factors associated with HIV spontaneous control in relation to HCV status were analysed in persistent and transient HIV-controllers with anti-HCV positive (n = 202 and n = 138 respectively) in comparison with 1700 HCV positive non HIV-controllers recruited from January 1981 up to March 2018, bivariate and multivariate analyses, following a logistic regression model, were applied. In addition, the factors related to the loss and time to lose HIV-controller status were explored (n = 744) using Log rank test and Kaplan-Meier curves, in this case the multivariate analysis consisted in a Cox regression model. Results: A higher frequency of HCV spontaneous clearance was found in persistent HIV-controllers (25.5%) compared to non-controllers (10.2%). After adjusting for potential confounders, as sex, age, HIV transmission risk, [CD4.sup.+] T-cell nadir and time of follow-up, HCV clearance was independently associated with persistent HIV spontaneous control (p = 0.002; OR (95% Cl) = 2.573 (1.428 to 4.633) ), but not with transient spontaneous control (p = 0.119; 1.589 (0.888 to 2.845) ). Furthermore, persistent HIV-controllers were more likely to spontaneously clear the HCV in comparison with transient controllers (p = 0.027; 0.377 (0.159 to 0.893). Finally not to lose or lengthen the time of losing this control was independently associated with HCV spontaneous clearance (p = 0.010; 0.503 (0.297 to 0.850). Conclusions: This study shows an association between spontaneous persistent HIV-control and HCV spontaneous clearance. The study findings support the idea of preserved immune mechanisms in persistent HIV control implicated in HCV spontaneous clearance. These results highlight persistent HIV-controllers but not transient controllers as a good model of functional HIV cure. Keywords: HIV; HCV; HIV-controllers; persistent; transient; HCV spontaneous clearance Additional information may be found under the Supporting Information tab for this article.

Background: This study evaluated titers and amplitudes of anti-E2 antibodies (anti-E2-Abs) and neutralizing antibodies against hepatitis C virus (HCV; anti-HCV-nAbs) in HIV/HCV-coinfected individuals over five years after successful HCV treatment completion. Methods: We retrospectively analyzed 76 HIV/HCV-coinfected patients achieving sustained virologic response post-HCV treatment. Plasma levels of anti-E2-Abs and anti-HCV-nAbs against five HCV genotypes (Gt1a, Gt1b, Gt2a, Gt3a, and Gt4a) were determined using ELISA and microneutralization assays, respectively. Statistical analyses comparing the three follow-up time points (baseline, one year, and five years post-HCV treatment) were performed using generalized linear mixed models, adjusting p-values with the false discovery rate (q-value). Results: Compared to baseline, anti-E2-Abs titers decreased at one year (1.9- to 2.3-fold, q-value < 0.001) and five years (3.4- to 9.1-fold, q-value < 0.001) post-HCV treatment. Anti-HCV-nAbs decreased 2.9- to 8.4-fold (q-value < 0.002) at one year and 17.8- to 90.4-fold (q-value < 0.001) at five years post-HCV treatment. Anti-HCV-nAbs titers against Gt3a were consistently the lowest. Nonresponse rates for anti-E2-Abs remained low throughout the follow-up, while anti-HCV-nAbs nonresponse rates increased 1.8- to 13.5-fold (q-value < 0.05) at five years post-HCV treatment, with Gt3a showing the highest nonresponse rate. Conclusions: Humoral immune responses against HCV decreased consistently one and five years post-HCV treatment, regardless of HCV genotype and previous HCV therapy or type of treatment (IFN- or DAA-based therapy). This decline was more pronounced for anti-HCV-nAbs, particularly against Gt3. [ABSTRACT FROM AUTHOR]

We studied the association of mitochondrial DNA (mtDNA) haplogroups with weight and body mass index (BMI) gain at 96 weeks in 1019 treatment-naive persons with HIV (PWH) who initiated first-line antiretroviral therapy (ART) since 2014. The mean increase in weight and BMI over the study period was 2.90 kg and 0.98 kg/m2, respectively. We found a significant adjusted association between the major UK mtDNA haplogroup and lower weight and BMI increase at 96 weeks after ART initiation. Our findings reveal a potential role for mitochondrial genetics in the complex phenomenon of weight gain after initial ART in PWH. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus (HCV) infection remains a global health challenge, with millions of people affected annually. Current diagnostic methods, reliant on antibody screening and viral RNA detection, are complex, costly, and often inaccessible, particularly in resource-limited settings. Aim: Development of a lateral flow immunochromatography-based assay for detecting the highly conserved hepatitis C core antigen (HCVcAg). Methods: The assay relies on the interaction of four highly specific and cross-reactive monoclonal antibodies with recombinant HCVcAg from five different genotypes in a double antibody sandwich format. Latex and colloidal gold were evaluated as detector nanoparticles. Results: Extensive evaluation of 32 antibody combinations led to identifying the most sensitive antibody pairs. The chosen assay, named LN17, demonstrated a target sensitivity of 10 ng/strip, with potential clinical implications for detecting HCV. Furthermore, the study examined matrix effects in serum samples, providing valuable insights for future clinical application. Conclusions: The developed assay holds promise as a rapid, cost-effective, and user-friendly tool to enhance accessibility to hepatitis C screening, especially in high-risk populations and resource-limited environments. [ABSTRACT FROM AUTHOR]