Search Results (1,193)

Background/Objectives: Grey zone serologic results in blood donor screening pose challenges for transfusion safety, donor management, and blood supply sustainability. In Saudi Arabia, standardized national protocols for managing grey zone outcomes remain lacking. This study aimed to evaluate the prevalence and follow-up outcomes of grey zone serologic results among blood donors at a Saudi hospital over a five-year period. Methods: Serological screening results of six transfusion-transmissible infections (TTIs) markers were extracted alongside nucleic acid testing (NAT) results for HBV, HCV, and HIV. The grey zone was defined as a signal-to-cutoff (S/CO) of 0.90–0.99. Repeat and follow-up results, including subsequent donations, were assessed for seroconversion. Results: A total of 48,241 donations from 38,524 donors were analyzed. Anti-HBc showed the highest reactivity (n = 2312; 4.8%), followed by HbsAg (n = 2292; 0.31%) and syphilis (n = 218; 0.5%). Grey zone results were rare, and most frequent in anti-HBc (n = 76; 0.16%), HCV (n = 39; 0.08%), and HBsAg (n = 28; 0.06%). Grey zone-to-reactive conversion upon subsequent donation was rare. Three donors who initially tested in the grey zone for anti-HBc later tested reactive in subsequent donations, but their HBV NAT remained negative. Conclusions: While grey zone outcomes were infrequent, a subset involving HBV markers showed low-level reactivity on repeat testing. For other TTIs markers, grey zone results likely reflected assay variability rather than true infection. We propose a six-month temporary deferral with follow-up serologic and NAT testing, allowing conditional re-entry for donors with consistently non-reactive results, supporting both transfusion safety and a more sustainable donor pool. Full article

Viral infection is a significant cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (Allo-HSCT), largely due to its impact on and interaction with immune reconstitution. Both innate and adaptive immunity are essential for effective viral control, yet their recovery post-transplant is often delayed or functionally impaired. Emerging evidence suggests genetic variation, particularly polymorphisms in the IL28B gene (encoding IFN-λ3), as a critical factor influencing the quality and timing of immune responses during the early post-transplant period. This review explores the role of IL28B polymorphisms in shaping antiviral immunity, in general, as well as after Allo-HSCT. IL28B variants have been implicated in modulating interferon-stimulated gene (ISG) expression, natural killer (NK) cell activity, and type I/III interferon signaling, all central components of innate immune defense against viral infections. Furthermore, IL28B polymorphisms, particularly rs12979860, have been shown in both general populations and limited HSCT cohorts to alter T cell response and interferon production, affecting reactivation and clearance of multiple viruses such as cytomegalovirus (CMV), hepatitis B virus (HBV), hepatitis C virus (HCV), Epstein–Barr virus (EBV), COVID-19, and BK polyomavirus (BKPyV) as well as Graft vs. Host disease, thereby affecting adaptive immune reconstitution and long-term viral control. Understanding how IL28B genotype alters immune dynamics in transplant recipients could enhance risk stratification for CMV and other diseases and inform personalized prophylactic or therapeutic strategies. Therefore, this review highlights IL28B as a promising biomarker and potential immunoregulatory target in the management of viral infection post-Allo-HSCT. Full article

RNA virus populations exist as quasispecies-complex, dynamic clouds of closely related but genetically diverse variants generated by high mutation rates during replication. Assessing quasispecies structure and diversity is crucial for understanding viral evolution, adaptation, and response to antiviral treatments. However, comparing single quasispecies observations from individual biosamples, especially at different infection or treatment time points, presents statistical challenges. Traditional inferential tests are inapplicable due to the lack of replicate observations, and resampling-based approaches such as the bootstrap and jackknife are limited by biases and non-independence, particularly for diversity indices sensitive to rare haplotypes. In this study, we address these limitations by applying the delta method to derive analytical variances for a set of quasispecies structure indicators specifically designed to assess the quasispecies maturation state. We demonstrate the utility of this approach using high-depth next-generation sequencing data from hepatitis C virus (HCV) quasispecies evolving in vitro under various conditions, including free evolution and exposure to antiviral or mutagenic treatments. Our results reveal that with highly fit HCV quasispecies, sofosbuvir inhibits quasispecies genetic diversity, while mutagenic treatments accelerate maturation, compared to untreated controls. We emphasize the interpretation of results through absolute differences, log-fold changes, and standardized effect sizes, moving beyond mere statistical significance. This framework enables robust, quantitative comparisons of quasispecies diversity from single observations, providing valuable insights into viral adaptation and treatment response. The R code and session info with required libraries and versions is provided in the supplementary material. Full article

The COVID-19 pandemic disrupted progress towards global HCV elimination goals by interrupting essential health services in Canada and globally. We aimed to evaluate the effect of the pandemic on hepatitis C virus (HCV) testing rates in a population-based cohort study in Ontario using health administrative data. All residents with records of either HCV antibody or ribonucleic acid (RNA) tests were included. Monthly testing rate per 1000 population were compared during the pre-pandemic (01/01/2015–29/02/2020) and pandemic (01/03/2020–31/12/2022) periods using interrupted time series models, stratified by sex, homelessness, human immunodeficiency virus (HIV), and immigration status, and people who inject drugs (PWID). The HCV testing rate followed a statistically significant upward trend before the pandemic, dropping at its onset with 1.38/1000 fewer individuals initiating testing monthly. Compared to counterfactual estimates, the observed monthly number of people tested per 1000 population was lower by 1.41 (95% CI: 1.18–1.64) in 2020 (May–Dec), 1.17 (95% CI: 0.99–1.36) in 2021, and 1.41 (95% CI: 1.22–1.59) in 2022, corresponding to relative reductions of 47%, 34%, and 41%, respectively. Testing rates remained below expected levels across all subgroups throughout 2020–2022, with the greatest absolute declines observed among people co-infected with HIV, people experiencing homelessness, and PWID. Tailored, equity-focused interventions are needed to address these persistent gaps in HCV testing, without which Canada’s progress toward its 2030 elimination targets remains at risk. Full article

Background/Objectives: Hepatocellular carcinoma (HCC) remains a leading cause of global cancer mortality, with increasing incidence and persistently poor survival. Hepatitis C virus (HCV) is a major risk factor for HCC, and while the advent of direct-acting antivirals (DAAs) has significantly altered HCV-related hepatocellular cancer (HCC-HCV) risk, the global burden remains substantial. With the World Health Organization (WHO) aiming to reduce hepatitis-related deaths by 2030, we set out to evaluate global HCC-HCV trends from 1990 to 2021, stratified by sex, WHO region, and sociodemographic index (SDI), using data from the Global Burden of Disease (GBD) 2021 study. Methods: We analyzed age-standardized incidence (ASI), deaths, and disability-adjusted life years (DALYs) due to HCV-HCC from 1990 to 2021 using GBD 2021 data. Trends were stratified by WHO region, sociodemographic index (SDI), and sex. Joinpoint regression modeling was used to identify statistically significant temporal inflection points and calculate the annual percent change (APC) in unique time segments and average annual percent change (AAPC) over the entire study period (1990 to 2021). Results: Globally, deaths and DALYs attributable to HCV-HCC increased over the study period while ASI declined modestly. The region of the Americas exhibited the highest AAPC in all three metrics, potentially driven by an aging HCV-infected population, rising comorbidities (e.g., obesity, diabetes), and improved case detection. Nevertheless, on a global level, high-SDI regions showed the most favorable trends, particularly after 2016, likely reflecting the earlier adoption of DAAs and a differential success of WHO goals. Lower-SDI regions continued to exhibit increasing burden. Notably, ASI began to rise again between 2019 and 2021, suggesting an ongoing need to critically evaluate and restructure our approach to reducing HCV and HCV-HCC. Conclusions: Our findings underscore the urgent need for equity-driven, region-specific strategies to achieve better control of this highly morbid disease. Full article

Hepatitis B virus (HBV) remains a major global health challenge, with over 296 million people chronically infected worldwide. Despite the availability of antiviral therapies, a functional cure is rarely achieved, highlighting the need for novel therapeutic strategies. RNA 5-methylcytosine (m⁵C) is a pivotal epitranscriptomic mark implicated in RNA stability, transport, and translation. Emerging evidence shows that m⁵C is conserved within HBV RNA and plays critical roles in the viral life cycle. This review provides a comprehensive overview of the molecular mechanisms governing m⁵C deposition and recognition, summarizes recent advances in m⁵C biology, and highlights the emerging role of epitranscriptomic m⁵C regulation in HBV infection. We discuss the identification of HBV-specific m⁵C sites, the functions of key regulatory enzymes, and their interplay in viral RNA stabilization and evasion of innate immune responses. Interplay between m⁵C and other RNA modifications—particularly N6-methyladenosine (m⁶A)—is examined alongside virus-specific m⁵C regulation in EV71, HIV, HCV, EBV, and SARS-CoV-2. Potential links between m⁵C dysregulation and HBV-induced hepatocarcinogenesis are outlined, and emerging therapeutic strategies targeting the m⁵C machinery are highlighted. Together, these insights position the epitranscriptomic landscape as a promising avenue for innovative antiviral strategies. Full article

Systemic or localized infections increase the risk of venous thromboembolism (VTE). All types of infection can elevate the risk of VTE thrombosis, although some appear to increase risk more than others. In the current narrative review, we seek to overview the available evidence related to the epidemiology of VTE caused by infections. We focused on patients with infection in community setting or hospitalized, on patients with COVID-19, HIV infection, tuberculosis, HCV infection, and CMV infection, as well as on individuals with other types of infection that might increase the risk of VTE. Moreover, we tried to evaluate how the risk of VTE in person with different types of infections could be addressed in clinical practice with the use of anticoagulants. Extended VTE prophylaxis may not be warranted for all infections, but may be very helpful for some, such as those with intra-abdominal infection, systemic bloodstream infection, lower respiratory infection, and symptomatic urinary tract infection. Full article

Background/Objectives: Identifying dietary factors influencing liver cancer is crucial for developing preventive measures. While tea polyphenols have demonstrated cancer-preventive activities in animal models, the evidence in humans is not definitive. This study aims to explore the association between tea consumption and liver cancer, as well as the interaction between tea drinking and other risk factors, in China, a country with a high incidence of liver cancer and substantial tea consumption. Methods: A population-based case–control study was conducted in Jiangsu Province from 2003 to 2010. Socio-demographic data, history of tea consumption, and serum markers of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections were evaluated. Unconditional logistic regression was used to examine the associations between tea consumption and the odds of liver cancer. Potential interactions between tea consumption and other major liver cancer risk factors were assessed. Results: A total of 2011 incident liver cancer cases and 7933 controls were included in the analysis. Regular tea drinking showed an inverse association with the risk of liver cancer compared with those who never drank tea (OR: 0.79; 95% CI: 0.63–0.99). Current tea drinking showed an inverse association with liver cancer (OR: 0.51; 95% CI: 0.39–0.66), while former tea drinking showed a positive association (OR: 3.56; 95% CI: 2.42–5.23). Current tea consumption was inversely associated with liver cancer incidence among both hepatitis B surface antigen (HBsAg) positive (OR: 0.45; 95% CI: 0.28–0.73) and HBsAg negative participants (OR: 0.51, 95% CI: 0.36–0.73), among both never and ever tobacco smokers, ever alcohol drinkers (OR: 0.46; 95% CI: 0.33–0.63), and among those without family history of liver cancer. Multiplicative and additive interactions were observed between tea drinking and HBsAg, alcohol consumption, and history of raw water drinking. Conclusions: Tea consumption is inversely associated with the development of primary liver cancer, with potential interactions involving HBV infection, alcohol consumption, and raw (unsafe) water drinking. Increasing tea consumption—particularly among high-risk populations such as individuals who consume alcohol—may serve as an additional preventive measure for liver cancer. This should be considered alongside established strategies, including HBV vaccination, alcohol cessation, and avoidance of drinking raw water, to help reduce liver cancer risk. Full article

Blood transfusion remains vital in healthcare but poses risks, particularly from transfusion-transmissible viral infections (TTVIs). This study aims to determine the seroprevalence of HIV, HBV, and HCV among blood donors in Borgou (Benin) in 2023. This prospective, cross-sectional study involved voluntary, non-remunerated blood donors recruited via mobile campaigns and at a fixed site from January to December 2023. Screening for HIV, HBV, and HCV was performed using fourth-generation ELISA (Biorad^®). Data analysis used SPSS with Chi-square test of independence (p < 0.05), and multiple logistic regression identified independent risk factors. Among 9646 donors, 87.80% were male (sex ratio 7.19), mostly aged 18–24 (55.93%), with students forming the largest group (58.67%). Mobile units collected 70.80% of donations; 52.60% were repeat donors. Overall TTVI seroprevalence was 9.35%, with HBV (6.29%) most common, followed by HCV (1.78%) and HIV (1.28%). Chi-square tests revealed significant associations between serostatus and donor status, donation site, and occupation, but not sex. Logistic regression identified independent risk factors: age, donor status, and donation site were significantly associated with HIV infection; male sex, older age, occupation, and donor status predicted HBV infection; and only donor status was significantly associated with HCV infection. These findings highlight the need for targeted recruitment and awareness strategies to improve transfusion safety. Full article

Hepatic viruses, such as hepatitis B and C (HBV and HCV), evade immune defenses and drive liver cirrhosis and cancer. They remain a major global health burden, requiring deeper research into immune responses; specifically, adaptive immunity. This study aims to analyze T cellular subsets in chronic HBV and HCV infection and investigate their potential role in the immunopathogenesis of these conditions. Methods: For our study, we collected 123 blood samples taken from patients infected with HCV (n = 36) and HBV (n = 34) and healthy volunteers (n = 53). With the use of flow cytometry, we assessed levels of CD4+ and CD8+ minor T cell subpopulations (naïve, central, and effector memory cells (CM and EM), terminally differentiated EM (TEMRA), Th1, Th2, Th17, Tfh, Tc1, Tc2, Tc17, Tc17.1). Results: Despite similar total CD4+ T cell frequencies across chronic HCV, HBV, and healthy groups, patients with hepatitis showed elevated TEMRA, EM, and CM subsets alongside depleted naïve Th cells and specific CM subpopulations compared to controls. Patients with chronic HCV and HBV showed elevated CD8+ T cell frequencies versus controls, with disease-specific shifts: reduced EM CTLs but increased TEMRA CTLs, Tc1/Tc17.1 depletion (notably Tc17.1 in HCV), and higher Tc2 levels. Conclusions: Viral clearance in HBV and HCV requires a delicate balance between immunity and viral activity. Despite similar T cell frequencies (CD3+/CD4+/CD8+), minor subsets revealed distinct patterns differentiating HCV, HBV, and healthy controls. Full article

Hepatitis D virus (HDV) infection remains a major cause of severe liver disease among hepatitis B virus (HBV)-infected patients, contributing to accelerated progression to cirrhosis and hepatocellular carcinoma. Pegylated interferon-α remains the first-line therapy for chronic HDV infection in most cases. However, despite its approval for HBV and hepatitis C virus (HCV) infections, its use in HDV is largely driven by a lack of other options and is constrained by its limited efficacy, suboptimal durability of response, and a substantial side effect profile. Meanwhile, bulevirtide, an entry inhibitor, became the first agent to be approved for use in chronic HDV infections by the European Medicines Agency (EMA), and several other therapies are currently being investigated as well. In this review, we provide updates on recent advancements in HDV treatment and novel therapies. Full article

Background/Objectives: Chronic hepatitis C virus (HCV) infection is associated with a wide spectrum of extrahepatic manifestations, involving the immune, dermatologic, endocrine, vascular, and neuropsychiatric systems. Among these, mixed cryoglobulinemic vasculitis (CryoVas) remains one of the most clinically relevant complications. This work aims to provide a structured overview of HCV-related extrahepatic conditions and to analyze the clinical and virological outcomes of direct-acting antivirals (DAAs) in CryoVas patients. Methods: We first categorized and reviewed extrahepatic manifestations of HCV across five major domains: immune, inflammatory/metabolic/vascular, dermatological, thyroid, and neuropsychiatric. Subsequently, we conducted a comparative analysis of five clinical studies evaluating the impact of DAA therapy in patients with CryoVas. Data on demographics, clinical symptoms, treatment regimens, sustained virological response, and clinical response were extracted and summarized. Results: HCV was found to be associated with numerous extrahepatic conditions, including mixed cryoglobulinemia, non-Hodgkin lymphoma, autoimmune thyroiditis, insulin resistance, and neurocognitive symptoms. In the CryoVas subgroup analysis, virological response rates were uniformly high (88.9–100%), but clinical remission varied significantly. Complete response ranged from 39% to 90%, highlighting a discrepancy between viral eradication and extrahepatic symptom resolution. These findings underscore the need for individualized follow-up and further investigation into persistent immunological dysfunction post-sustained virological response (SVR). However, clinical outcomes were more variable: complete response (CR) varied between 39% and 90%, partial response (PR) ranged from 4% to 42%, and no response (NR) was reported in 0% to 40% of cases. Although significant improvement in key manifestations such as purpura, arthralgia, and neuropathy was frequently observed, a subset of patients continued to exhibit residual or refractory symptoms despite achieving SVR. Conclusions: HCV infection exerts multisystemic effects that extend beyond liver pathology. While DAAs offer near-universal virological clearance, the heterogeneous clinical response in CryoVas underscores the need for closer monitoring of extrahepatic outcomes. Future research should assess whether combining DAAs with immunomodulatory strategies can improve symptom control and long-term outcomes in patients with severe or refractory CryoVas. Full article

The precipitation of cryoglobulins, serum immunoglobulins, below 37 °C defines the clinical cryoglobulinemic syndrome, a systemic vasculitis usually characterized by purpura, weakness, and arthralgia. In most cases, this condition is associated with chronic infection by the hepatitis C virus (HCV) and can evolve into B-cell dysregulation and malignancies. The current literature on non-HCV-associated cryoglobulinemia is very limited, and little is known about the immunological and serological profile of affected patients. The cryoglobulinemic syndrome not associated with HCV infection is often found concomitantly with other infections, autoimmune diseases, and B-cell lymphoproliferative disorders. The cryoprecipitation of fibrinogen has been described as a rare disorder, perhaps underestimated and not fully understood, causing thrombotic occlusion and ischemia in different rheumatic disorders. Cold temperature plays a pathogenetic role in autoimmune hemolytic anemias, in which the presence of cold agglutinins produced by B cells at the lymphoplasmacytic cell stage may promote agglutination of red blood cells in the coldest parts of the circulation, even at mild room temperatures, undergoing hemolysis. Laboratory methods for the detection and quantification of cryoproteins are downright critical, and their concurrent detection is pivotal for the diagnosis. In this review, we summarize the clinical involvement of cryoglobulins, cryofibrinogen, and cold agglutinins in non-HCV autoimmune diseases, underlining the crucial steps of the most employed analytic methods. Full article

The global elimination of hepatitis C virus (HCV) has been prioritized by the World Health Organization (WHO) as a key public health target, with a deadline set for 2030. This initiative aims to significantly reduce both new infection rates and HCV-associated mortality. A major breakthrough in achieving this goal has been the development of direct-acting antiviral agents (DAAs), which offer cure rates exceeding 95%, along with excellent safety and tolerability. Nevertheless, transmission via parenteral routes continues to be the dominant pathway, particularly among high-risk groups, such as individuals who inject drugs, incarcerated populations, those exposed to unsafe medical practices, and healthcare professionals. Identifying, monitoring, and delivering tailored interventions to these groups is crucial to interrupt ongoing transmission and to reduce the burden of chronic liver disease. On a global scale, several nations have demonstrated measurable progress toward HCV elimination, with some nearing the targets set by WHO. These achievements have largely resulted from context-adapted policies that enhanced diagnostic and therapeutic access while emphasizing outreach to vulnerable communities. This review synthesizes current advancements in HCV prevention and control and proposes strategic frameworks to expedite global elimination efforts. Full article

Co-infections pose significant challenges not only clinically, but also in terms of simultaneous diagnoses. The development of sensitive, multiplexed analytical platforms is critical for accurately detecting viral co-infections, particularly in complex biological environments. In this study, we present a mass spectrometry (MS)-based detection strategy employing a target-triggered hybridization chain reaction (HCR) to amplify signals and in situ photocleavable mass tags (PMTs) for the simultaneous detection of multiple targets. Hairpin DNAs modified with PMTs and immobilized loop structures on magnetic particles (Loop@MPs) were engineered for each target, and their hybridization and amplification efficiency was validated using native polyacrylamide gel electrophoresis (PAGE) and laser desorption/ionization MS (LDI-MS), with silica@gold core–shell hybrid (SiAu) nanoparticles being employed as an internal standard to ensure quantitative reliability. The system exhibited excellent sensitivity, with a detection limit of 415.12 amol for the hepatitis B virus (HBV) target and a dynamic range spanning from 1 fmol to 100 pmol. Quantitative analysis in fetal bovine serum confirmed high accuracy and precision, even under low-abundance conditions. Moreover, the system successfully and simultaneously detected multiple targets, i.e., HBV, human immunodeficiency virus (HIV), and hepatitis C virus (HCV), mixed in various ratios, demonstrating clear PMT signals for each. These findings establish our approach as a robust and reliable platform for ultrasensitive multiplexed detection, with strong potential for clinical and biomedical research. Full article