Search Results (502)

Background: The Canadian HIV Cure Enterprise (CanCURE) is a pan-Canadian research collaboratory, investigating approaches for achieving sustainable HIV remission. In preparation for the next research cycle, CanCURE researchers and the Community Advisory Board (CAB) co-designed a web-based survey to identify HIV research priorities from the perspective of people with HIV (PWH) in Canada. The current study examined gender-based differences in these priorities. Methods: From August to December 2024, we recruited PWH across Canada through community organizations and community members. We collected data using REDCap electronic data capture tools hosted at The Research Institute of the McGill University Health Centre. The survey included 36 demographic questions, 16 questions related to general knowledge about HIV and HIV cure-related concepts, and 21 questions ranking research priorities. Knowledge questions were multiple choice, while priorities could be ranked on a scale. We summarized participant characteristics via descriptive statistics, and the research priorities were further stratified according to gender. Results: Of 109 participants, 48.6% self-identified as men, 46.8% as women, and 4.6% as two-spirit, non-binary, agender, or other. The median age was 53 years old. Approximately one-third of participants had lived with HIV for ≤14 years, one-third for 15–24 years, and one-third for ≥25 years. Overall, the median knowledge score of respondents was 79%. Among the 78 participants with prior HIV research experience, three times as many men (61.1%) as women (19.0%) participated in interventional studies involving medication or medical procedures. Men ranked preventing HIV transmission to partners as a priority, studying where the virus hides as the second, and avoiding high comorbidity risks as the third. In contrast, women ranked not having to take pills daily as a priority and avoiding higher risks for comorbidities as the second priority. Both genders equally valued expanding community involvement in HIV cure research. However, men focused more on integrating social and behavioural research, while women emphasized the need for diverse ethnic representation in research. Conclusions: Although both men and women share some common priorities regarding HIV cure research, there are notable gender differences in their specific concerns. Furthermore, a significant gender gap in participation in interventional studies, essential for advancing HIV cure research, highlights the importance of aligning research priorities with concerns of both genders. Full article

Chronic hepatitis C virus (HCV) infection remains a major global health burden, responsible for substantial morbidity and mortality despite the advent of curative antiviral therapy. HCV induces hepatic injury and carcinogenesis through direct viral effects, persistent inflammation, oxidative stress, and metabolic disturbance. The introduction of direct-acting antivirals (DAAs) has revolutionized therapy, achieving sustained virologic response rates exceeding 95% and transforming HCV from a chronic, progressive disease into a curable infection. Nevertheless, viral eradication does not fully normalize hepatic or systemic risk. Patients with advanced fibrosis or cirrhosis continue to face an elevated incidence of hepatocellular carcinoma (HCC) and other complications, reinforcing the need for long-term monitoring. This review summarizes current knowledge of the molecular mechanisms underlying HCV-mediated carcinogenesis, the partial restoration of hepatic homeostasis following DAA-induced cure, and the clinical implications for surveillance and management in the post-HCV era. By integrating insights from molecular virology, immunopathogenesis, and clinical hepatology, the review highlights how persistent epigenetic and inflammatory footprints may sustain oncogenic potential even after viral clearance. A comprehensive understanding of these processes is essential for optimizing HCC prevention strategies, guiding surveillance policies, and advancing future therapeutic innovations aimed at complete hepatic recovery. Full article

Background and Objectives: Patients who undergo hepatitis virus testing may remain unaware of their results in the absence of clinician feedback, particularly from non-specialists. To address this issue, we introduced patient-directed test result reports and evaluated their effectiveness in promoting physician responses among non-specialists. Materials and Methods: Distribution of hepatitis virus test result reports began on 22 August 2022 at the National Hospital Organization Disaster Medical Center in Japan. The study included all patients who underwent hepatitis testing, excluding those whose tests were ordered by gastroenterologists or screening physicians. The numbers of tests performed and reports distributed were obtained from electronic medical records. Results: Between August 2022 and August 2025, 30,700 patients underwent hepatitis B surface antigen (HBsAg) and/or hepatitis C virus antibody (HCV-Ab) testing, and 11,797 individuals received test result reports. In the most recent one-year period (September 2024–August 2025), the report distribution rate was 49.7%, unaffected by test positivity. Compared with the year before report implementation, the referral rates to gastroenterologists increased significantly for both HBsAg-positive (11.4% to 34.5%) and HCV-Ab-positive cases (7.7% to 25.2%; p < 0.01). Documentation of test results and confirmation of clinical cure or ongoing treatment by the ordering physician both improved. Cases without physician response decreased markedly (from 61.4% to 23.6% in HBsAg-positive patients and from 59.3% to 24.5% in HCV-Ab-positive patients; p < 0.01 for both). Conclusions: Distribution of dedicated hepatitis virus test result reports improved awareness among non-specialist physicians and contributed to better management of test-positive patients. Full article

Background and Objectives: Hepatitis C virus (HCV) remains a significant cause of chronic liver disease worldwide. While direct-acting antivirals achieve high cure rates, the interplay between viral load, gender, and routine laboratory parameters remains unclear. This study aimed to investigate hematological, biochemical, and coagulation profiles, as well as derived non-invasive indices, in HCV-infected patients, stratified by gender and viremia levels. Materials and Methods: This retrospective study included 367 patients with HCV infection (223 males and 144 females). Patients were divided into four groups: high viremia males (hiVM), high viremia females (hiVF), low viremia males (loVM), and low viremia females (loVF), using 800,000 IU/mL as the threshold. Routine hematological, biochemical, and coagulation tests were conducted, and derived indices (FIB-4, APRI, AST/ALT ratio, PLR, NLR, SII, AISI, PNI, HALP, PAR, NAR) were calculated. Results: Significant gender- and viremia-specific differences were observed. hiVM showed higher erythrocyte indices and altered coagulation parameters, whereas hiVF had increased lymphocyte counts and AST/ALT ratio elevation. loVM displayed reduced hemoglobin and hematocrit, along with worse coagulation results. Biochemical analysis revealed gender differences in GGT, bilirubin, and albumin levels. Among derived indices, FIB-4 and APRI were higher in loVM, while SII and PLR were elevated in loVF. At the second visit after 17±4 weeks, when patients had no detectable HCV DNA in the peripheral blood, most indices improved significantly across groups. Conclusions: HCV infection affects laboratory profiles depending on gender and viremia levels. Non-invasive indices from routine tests offer valuable insights into inflammatory and nutritional status. Using these indices alongside traditional markers may aid hypothesis generation or clinical assessment and help prioritize further assessment for HCV patients. Full article

Psittacine bornavirus type-4 (PaBV-4) causes proventricular dilatation disease and death among diverse birds, most notably caged parrots and related species, with no known cure or vaccine. Infected birds can shed virus in fecal matter, urine, and feather dander but it is unknown how well PaBV-4 survives outside of the host. This study focused on assessing the persistence of PaBV-4 in common environmental situations. The presence of viral RNA was examined in aqueous solutions at varying temperatures and recovery from typical avian husbandry materials (plastic, wood, metal, and cloth). Viral RNA persistence in aqueous samples was found to be 3 weeks at 37 °C, 2 months at 24 °C (room temperature), and 3 months at 4 °C. Viral RNA was also recovered from plastic and metal surfaces up to 72 h after inoculation. Also examined were disinfection protocols comparing coverage versus contact time for a reduction in viral RNA. Complete coverage by the disinfecting agent was more important for preventing recovery of viral RNA. Additionally, PaBV-4 RNA was transferable by paper towel. These results provide the first evidence of the robust nature of PaBV-4 in an aqueous environment and show that cleaning protocols need to be carefully curated to limit possible viral spread. Full article

Background/Objectives: Phosphatidylinositol (PI) species are bioactive lipids implicated in liver fibrogenesis. Hepatitis C virus (HCV) relies on host lipid metabolism for infection. The relationship between serum PI profiles, chronic HCV, and liver injury remains incompletely defined. Methods: Fourteen PI species were quantified by direct flow injection–tandem mass spectrometry (FIA–MS/MS; triple quadrupole) in serum from 178 patients with chronic HCV at three time points: before treatment and at weeks 4 and 12 after starting direct-acting antiviral (DAA) therapy. Results: At baseline, PI 34:1, 36:1, and 36:3 were higher in patients with ultrasound-diagnosed cirrhosis than in those without, whereas PI 38:4, 40:5, and 40:6 were lower. In non-cirrhotic patients, PI 36:3, 36:4, 38:3, 38:4, and 38:5 increased, while PI 40:5 and 40:6 declined at weeks 4 and 12 after therapy start. In cirrhosis, viral cure was not associated with changes in PI species. By the end of therapy, cirrhotic patients showed higher PI 36:3 and lower PI 38:4 than non-cirrhotic patients. Genotype 3a was associated with lower PI 38:3, 38:4, and 38:5; the reduction in PI 38:4 persisted to the end of therapy. Across time points, most PI species did not correlate with routine markers of liver injury or inflammation. Conclusions: HCV cure remodels the serum PI profile in non-cirrhotic patients. These findings suggest that altered PI profiles are primarily linked to HCV infection, supporting a role for PI lipids in viral propagation. Full article

Hepatitis B virus (HBV) represents a significant global health challenge, affecting over 254 million individuals and contributing to 1.1 million deaths from liver-related complications in 2022. The World Health Organization has set ambitious targets to reduce HBV infections and mortality by 2030. However, only a small proportion (13%) of infected individuals receives timely diagnosis and treatment. HBV elimination efforts necessitate substantial improvements in HBV diagnosis, particularly in identifying early-stage infections, occult HBV infections (OBI), and breakthrough cases. The hepatitis B surface antigen (HBsAg) is a key biomarker in HBV diagnosis, serving as a reliable indicator of infection status and treatment response. Conventional HBsAg assays, with a lower limit of detection (LoD) between 0.03 and 250 IU/mL, often fail to detect OBI and HBV reactivation. In contrast, ultrasensitive HBsAg assays, with an LoD as low as 0.005 IU/mL, can improve the identification of low concentration levels of HBsAg, facilitating earlier diagnosis, monitoring of therapeutic response, and assessment for functional cure. Research confirms the superiority of ultrasensitive assays in detecting HBV in cases missed by conventional assays, detecting NAT-yield samples, and enabling earlier detection of HBV reactivation. This review examines the challenges in HBV diagnostics and the clinical utility of ultrasensitive HBsAg assays in improving progress toward global HBV elimination. Full article

Direct-acting antivirals (DAAs) have transformed hepatitis C virus (HCV) management, offering high cure rates, favorable safety, and simplified regimens. Management in immunosuppressed patients remains challenging due to drug–drug interactions (DDIs). The objective of this review is to summarize clinical outcomes, safety, and pharmacologic considerations of DAA therapy in immunosuppressed patients, including solid organ transplant recipients and those on biological agents. We reviewed clinical studies, pharmacologic databases, and guidelines to characterize DAA classes, mechanisms, and relevant DDIs in immunosuppressed HCV patients. In transplant recipients, DAAs achieved sustained virological response (SVR) > 90% with minimal graft rejection. Safety profiles were favorable, and immunosuppressant dose adjustments were rarely needed. DDIs, particularly with calcineurin inhibitors (tacrolimus, cyclosporine), require careful monitoring due to variable trough-level effects. Evidence also supports the efficacy and safety of DAAs in patients on biological agents, without compromising SVR. Pharmacokinetic data indicate DAAs maintain antiviral activity across HCV genotypes in the presence of immunosuppressants, though mTOR inhibitors may alter efficacy in certain HCV genotypes. DAAs are highly effective and safe in immunosuppressed patients, achieving high SVR rates and potential graft survival benefits. Prospective studies are needed to assess DAA therapy in patients receiving biological agents and to optimize co-administration strategies with immunosuppressive agents. Full article

Chronic hepatitis B poses a serious threat to human health and life, and early diagnosis is essential to improving patient cure rates. Hepatitis B virus (HBV) and Alpha-fetoprotein (AFP) are two key biomarkers for diagnosing chronic hepatitis B. In this study, we propose a silicon nanowire array field effect transistor (SiNW-array FET) biosensor that enables highly sensitive, real-time, and low-cost joint detection of both HBV and AFP. The SiNW-array FET is fabricated using traditional micro-nano fabrication techniques such as self-limiting oxidation and anisotropic etching, and its morphology and electrical properties were tested. The results show that the diameters of the fabricated silicon nanowires (SiNWs) are uniform and the SiNW-array FET exhibits a strong output signal and high signal-to-noise ratio. Through specific chemical modification on the surface of SiNWs, the SiNW-array FET is highly sensitive and specific to HBV-DNA fragments and AFP, with ultralow detection limits of 0.1 fM (HBV-DNA) and 0.1 fg/mL (AFP). The detection curve of the SiNW-array FET exhibits good linearity within the HBV-DNA concentration range of 0.1 fM to 100 pM and AFP concentration range of 0.1 fg/mL to 1000 pg/mL. More importantly, the device could also detect HBV-DNA successfully in serum samples, laying a solid foundation for the highly sensitive clinical detection of chronic hepatitis B. Full article

HSV-2 is the main pathogen causing genital herpes, and its infection increases the infection and transmission of HIV-1. Currently, there are no vaccines to prevent HSV-2 infection or treatment that can fully cure it. Mining key host factors that regulate HSV-2 replication and elucidating their specific regulatory mechanisms are crucial for understanding virus–host interactions and discovering new antiviral targets. In the current study, we identified DDX43 as a cellular factor involved in the suppression of HSV-2 replication through comparative transcriptomic analyses of HSV-2-infected epithelial cells, followed by experimental validation. Comprehensive transcriptomic profiling revealed distinct host cellular gene expression patterns in HeLa and ARPE-19 cell lines post HSV-2 infection. Subsequent orthogonal partial least-squares discriminant analysis (OPLS-DA) pinpointed DDX43 as one of the principal mediators distinguishing the host response between HSV-2-infected HeLa and ARPE-19 cells. Furthermore, overexpression of DDX43 inhibited HSV-2 replication, whereas knockdown of endogenous DDX43 enhanced HSV-2 replication. Additional experiments revealed that human DDX43 inhibits HSV-2 replication in an interferon-independent manner. This study demonstrates that DDX43 serves as a host regulator against HSV-2 infection, underscoring the power of comparative transcriptomics in identifying novel host proteins that modulate viral replications. Full article

Herpes simplex virus type 1 (HSV-1) is a continuous health challenge, and current antiviral treatments cannot cure the virus. As life expectancy continues to increase worldwide, HSV-1 should remain a focus to minimize its associated health complications within the aging population. While often asymptomatic, HSV-1 causes oral and cutaneous lesions and establishes latency with periodic reactivation. Antivirals reduce symptoms but do not eradicate the virus. Emerging evidence links HSV-1 to Alzheimer’s disease (AD) via chronic neuroinflammation, amyloid-beta and tau accumulation, oxidative stress, and synaptic dysfunction, with viral proteins detected in AD-affected brain regions. This review assesses the current evidence for HSV-1 in dementia pathogenesis, examines antiviral strategies as potential neuroprotective interventions, and outlines the experimental models required to establish causality. Full article

Chronic hepatitis B virus (HBV) infection remains a major global health challenge, substantially contributing to liver-related morbidity and mortality. Background/Objectives: Developing therapeutic strategies that overcome immune tolerance and achieve functional cures is an urgent priority. Methods: In this study, we report a therapeutic vaccine comprising hepatitis B surface antigen (HBsAg) formulated with the dual adjuvant system CpG 1018S and QS-21. The immunogenicity and therapeutic efficacy of this vaccine were systematically evaluated in an rAAV8-HBV1.3-established chronic HBV mouse model. Results: The vaccine elicited a robust Th1-skewed immune response, characterized by elevated anti-HBs IgG2b titers and an increased IgG2b/IgG1 ratio. Notably, immunized mice showed markedly reduced circulating HBsAg levels. Mechanistically, the CpG 1018S and QS-21 adjuvant system enhanced dendritic cell activation, maturation, and antigen presentation, expanded HBV-specific CD4⁺ and CD8⁺ T cell populations, and attenuated the expression of the exhaustion markers TIM-3 and TIGIT. Additionally, immunized mice exhibited restored T cell polyfunctionality, with an increased secretion of effector cytokines, including TNF-α and IL-21. These responses collectively contributed to the reversal of T cell exhaustion and breakdown of immune tolerance, facilitating sustained viral suppression. Conclusions: Our findings demonstrate that the CpG 1018S/QS-21-adjuvanted vaccine induces potent humoral and cellular immunity against chronic HBV infection and represents a promising candidate for clinical chronic HBV (CHB) treatment. Full article

Chronic hepatitis B virus (HBV) infection remains a major global health burden, affecting millions and contributing significantly to liver-related morbidity and mortality. While substantial progress has been made in elucidating the virology and natural history of HBV, the management of chronic hepatitis B (CHB) continues to present clinical challenges. The development of potent nucleos(t)ide analogs and pegylated interferon has improved viral suppression and delayed disease progression, yet a definitive cure remains elusive due to the persistence of covalently closed circular DNA (cccDNA). Recent research has focused on novel antiviral agents, immunomodulatory therapies, and combination strategies aimed at achieving a functional cure. This review summarizes current therapeutic approaches, recent advancements, and emerging directions in CHB management. Full article

The burden of hepatitis delta virus (HDV) infection is currently unknown and may affect 12 to 72 million people distributed across various hot spots in different regions of the globe. Screening for antibodies to HDV infection in patients positive for the hepatitis B surface antigen (HBsAg) is generally available in most parts of the world, but systematic testing for HDV is needed. Chronic HDV infection is associated with a higher risk of progression to cirrhosis, liver failure, and hepatocellular carcinoma compared to hepatitis B virus (HBV) mono-infection. Bulevirtide is the recently available treatment against hepatitis delta. The results of efficacy studies and new drugs (lonafarnib) are under discussion. New therapeutic strategies are in development, revealing a critical need for valid next-generation treatments to cure HDV. Full article

Background/Objectives: Hepatitis B virus (HBV) infection poses a major global health challenge, with current therapies like nucleos(t)ide analogs and pegylated interferon alpha offering limited functional cure rates due to persistent HBsAg-driven immune tolerance. This study aimed to develop a targeted immunoadsorption system using a high-affinity humanized anti-HBsAg monoclonal antibody for efficient HBsAg and viral particle clearance, providing a novel approach to overcome therapeutic bottlenecks in chronic hepatitis B (CHB). Methods: A murine anti-HBsAg monoclonal antibody was humanized via complementarity-determining region grafting, resulting in HmAb-12 (equilibrium dissociation constant, K_D = 0.36 nM). A stable Chinese Hamster Ovary K1 (CHO-K1) cell line was established for high-yield expression (fed-batch yield: 8.31 g/L). The antibody was covalently coupled to agarose microspheres (coupling efficiency > 95%) to prepare the immunoadsorbent. Efficacy was evaluated through in vitro dynamic circulation assays with artificial sera and preclinical trials using an integrated blood purification system in two CHB participants. Clearance rates for HBsAg and HBV DNA were quantified, with safety assessed via blood component monitoring. Results: In vitro, a single treatment cycle achieved HBsAg clearance rates of 70.14% (high antigen load, >10⁵ IU/mL) and 92.10% (low antigen load, ~3000 IU/mL). Preclinically, one treatment session resulted in acute HBsAg reductions of 78.30% and 74.31% in participants with high and moderate antigen loads, respectively, alongside HBV DNA decreases of 65.66% and 73.55%. Minimal fluctuations in total protein and albumin levels (<15%) confirmed favorable safety profiles, with no serious adverse events observed. Conclusions: Preliminary findings from this study indicate that the HBsAg-specific immunoadsorption system can achieve efficient HBV antigen clearance with an initial favorable safety profile in a small cohort. These results support its further investigation as a potential therapeutic strategy for functional cure in CHB. Future work will focus on validating these findings in larger studies and exploring the system’s combinatory potential with existing blood purification platforms. Full article