Search Results (634)

Schizophrenia is a challenging multifactorial neuropsychiatric disease that involves interactions between genetic susceptibility and environmental insults. Increasing evidence implicates viral infections as significant environmental contributors, particularly during sensitive neurodevelopmental periods. This review synthesises current findings on the viral hypothesis of schizophrenia, encompassing a wide array of neurotropic viruses, including influenza viruses, herpesviruses (HSV-1 and 2, CMV, VZV, EBV, HHV-6 and 8), hepatitis B and C viruses, HIV, HERVs, HTLV, Zika virus, BoDV, coronaviruses (including SARS-CoV-2), and others. These pathogens can contribute to schizophrenia through mechanisms such as direct microinvasion, persistent central nervous system infection, immune-mediated neuroinflammation, molecular mimicry, and the disturbance of the blood–brain barrier. Prenatal exposure to viral infections can trigger maternal immune activation, resulting in cytokine-mediated alterations in the neurological development of the foetus that persist into adulthood. Genetic studies highlight the role of immune-related loci, including major histocompatibility complex polymorphisms, in modulating susceptibility to infection and neurodevelopmental outcomes. Clinical data also support the “mild encephalitis” hypothesis, suggesting that a subset of schizophrenia cases involve low-grade chronic neuroinflammation. Although antipsychotics have some immunomodulatory effects, adjunctive anti-inflammatory therapies show promise, particularly in treatment-resistant cases. Despite compelling associations, pathogen-specific links remain inconsistent, emphasising the need for longitudinal studies and integrative approaches such as viromics to unravel causal relationships. This review supports a “multi-hit” model in which viral infections interfere with hereditary and immunological susceptibilities, enhancing schizophrenia risk. Elucidating these virus–immune–brain interactions may facilitate the discovery of biomarkers, targeted prevention, and novel therapeutic strategies for schizophrenia. Full article

Coinfections with hepatitis C virus (HCV) or human immunodeficiency virus (HIV) among individuals with chronic hepatitis B (CHB) are associated with worse clinical outcomes but remain understudied due to their low prevalence and the sensitivity of associated data. This nationwide, cross-sectional study utilized claims data from the Korean Health Insurance Review and Assessment Service (2014–2021) to investigate the prevalence, comorbidities, treatment patterns, and liver-related complications among patients with HBV monoinfection, HBV/HIV, HBV/HCV, or triple coinfection. Among over 4.5 million patients with chronic hepatitis B, the prevalence of HIV and HCV coinfection ranged from 0.05 to 0.07% and 0.77 to 1.00%, respectively. Patients with HBV/HCV coinfection were older and had significantly higher rates of hypertension, diabetes, dyslipidemia, and major adverse liver outcomes, including hepatocellular carcinoma and liver transplantation, compared to other groups. HBV/HIV coinfection was more common in younger males and was associated with higher dyslipidemia. The use of HBV antivirals increased over time across all groups. These findings highlight the distinct clinical characteristics and unmet needs of coinfected populations, underscoring the importance of tailored screening and management strategies in HBV-endemic settings. Full article

Polyphenols are structurally diverse plant metabolites that have attracted significant interest. Their compositions are versatile, depending on their structures, including the number of rings in the polyphenol composition. Based on these attributes, polyphenols can be classified as flavanols, anthocyanins, flavones, phenolic acids, stilbenes, and lignans. Polyphenols mainly possess inhibition of viral replication, interference with viral protein synthesis, and modulation of immune responses, providing significant antiviral effects against several viruses, including herpes simplex virus, hepatitis C virus, and influenza. They are crucial for medical compounds in diverse, versatile treatments, namely in diabetes, cardiovascular disorders, cancer, and neurodegenerative problems. Plants are the primary source of bioactive molecules, which are valued for their anti-inflammatory, antioxidant, anticancer, and antiviral activities. Especially, polyphenols are extracted as the most abundant bioactive compounds of plants. Moreover, viral infections are one of the major factors in illnesses and diseases, along with bacteria and fungi. Numerous in vitro and in vivo studies report antiviral activity against SARS-CoV-2, Mayaro virus, dengue virus, herpesvirus, and influenza A virus, though clinical validation remains limited. Additionally, inhibition of viral entry, interference with viral replication, modulation of host immune response, and direct virucidal effects were examined. Full article

Current structural barriers experienced by First Nations in Canada shape access and engagement for testing and treatment of hepatitis C virus (HCV) infections. This non-systematic informative review considers transdisciplinary perspectives, regional data, and published literature connecting context to the disproportionate HCV burden experienced by First Nations populations in the prairie provinces of Canada, and offers examples of participatory and community-led initiatives working toward the elimination of HCV as a public health threat. First Nations in Canada are disproportionately impacted by chronic HCV infection, with a reported rate of newly diagnosed HCV cases in First Nations communities five times the respective rate in the general Canadian population in 2022. This review explores the reasons underlying the disproportionate burden of HCV infection. Significant over-representation of First Nations in the Canadian Prairies is seen in the major risk categories for HCV acquisition, and the impact of these risk factors is aggravated by barriers to accessing healthcare services and medication coverage. These barriers stem from the legacy of colonialism, discrimination, disenfranchisement, and are exacerbated by stigmatization, victimization, and racism in the justice and healthcare systems. Other contributory factors that impede access to care include inadequate healthcare clinic staffing and infrastructure in First Nations communities, and significant geographical distances between First Nations reserves and laboratories, pharmacies, and treating/prescribing healthcare providers. Recent recognition of historical harms and early steps towards nation-to-nation reconciliation, along with support for culturally connected, holistic, and First Nations-led wellness programs, instill hope that elimination strategies to eradicate HCV infection in First Nations populations will be successful in Canada. Full article

Torquetenovirus (TTV) is a ubiquitous, non-pathogenic DNA virus that has been suggested as a biomarker of immune competence, with the viral load correlating with the level of immunosuppression. However, by detecting non-intact viral particles, standard PCR-based quantification may overestimate the TTV viremia. To improve the clinical relevance of TTV quantification, in this study, we investigated the use of PMAxx™, a virion viability dye that selectively blocks the amplification of compromised virions. Serum samples from 10 Hepatitis C Virus-positive (HCV+) individuals, 81 liver transplant recipients (LTRs), and 40 people with HIV (PWH) were treated with PMAxx™ and analyzed for TTV DNA loads by digital droplet PCR (ddPCR). Furthermore, anti-SARS-CoV-2 IgG levels and neutralizing antibody (nAbs) titers were measured post-COVID-19 vaccination. Using ddPCR, the PMAxx™ treatment significantly reduced the TTV DNA levels in all the groups (mean reduction: 0.66 Log copies/mL), indicating the abundant presence of non-intact, circulating viral genomes. However, correlations between TTV DNA and SARS-CoV-2 IgG or nAbs were weak or absent in both PMAxx™-treated and untreated samples. These findings suggest that while PMAxx™ enhanced the specificity of TTV quantification, it did not improve the predictive value of TTV viremia at assessing vaccine-induced humoral responses. Full article

Hepatitis C virus (HCV) infection is a major public health concern, with more than 58 million people chronically infected worldwide. The management of HCV, once the domain of specialists only, has been revolutionized by the advent of direct-acting antiviral therapies. To reduce the burden of HCV in the United States (US), emphasis is now being placed on the involvement of primary care physicians in the management of HCV patients. Inclusion of more primary care providers in the HCV diagnosis and treatment initiatives can assist in achieving the goal of HCV elimination, especially in the medically underserved areas. To actively engage in the management of HCV, primary care providers must understand its epidemiology, risk factors, natural history, current treatment regimen, and potential complications. This manuscript reviews these key areas, along with presenting the cost-effectiveness of treatment and evidence-based guidelines for follow-up care in adults with chronic HCV infection who have undergone HCV treatment. Equipped with this foundational knowledge about HCV management, primary care physicians can play a vital role in eliminating HCV. Full article

Background: The advent of direct-acting antivirals (DAAs) has marked a significant milestone in the therapeutic landscape of hepatitis C, greatly improving treatment efficacy. A therapeutic regimen encompassing sofosbuvir (SOF), velpatasvir (VEL), and voxilaprevir (VOX) has demonstrated strong efficacy across all genotypes of the hepatitis C virus (HCV) and has recently been incorporated into the Korean healthcare system. This study aimed to evaluate the real-world efficacy and safety of these antivirals in the South Korean population. Methods: This prospective, multicenter, observational study enrolled patients with chronic HCV treated with SOF/VEL-based regimens at six hospitals between November 2022 and January 2024. DAA-naïve patients received SOF/VEL ± ribavirin for 12 weeks. Patients who had failed prior DAA therapy received SOF/VEL/VOX for 12 weeks. The primary endpoint was a sustained virological response at 12 weeks post-treatment (SVR12). Results: Among 101 patients treated with SOF/VEL, the mean age was 64.71 years, and 40.9% were male. Genotypes 1b and 2 were identified in 40.6% and 59.4% of patients, respectively. Two patients had a history of interferon-based treatment. The mean baseline HCV RNA level was 3,088,097 IU/mL. Cirrhosis was observed in 26.7% of patients (21.8% compensated; 5.0% decompensated). Of the 101 patients, 12 were lost to follow-up. Among the 89 patients who completed follow-up, SVR12 was achieved in 100.0% (89/89), including 5 patients with decompensated cirrhosis. In the SOF/VEL/VOX group, 17 patients were treated. The mean age was 61.84 years, 29.4% were male, and four had compensated cirrhosis. One patient was lost to follow-up. SVR12 was achieved in 100.0% (16/16) of the patients who completed follow-up. No serious adverse events (≥grade 3) were reported in either group during the DAA treatment period. Conclusions: In this first prospective real-world study in South Korea, SOF/VEL-based regimens demonstrated excellent efficacy and safety, achieving 100% SVR12 in the per-protocol population, including patients with cirrhosis and prior treatment failure. Full article

Psoriasis, a chronic immune-mediated inflammatory skin disorder, presents complex pathogenetic mechanisms potentially influenced by viral infections. This comprehensive study explored the possible interplay of resistance and viral infections among psoriasis patients using serological screening techniques. The investigation involved 90 patients aged 23–45 years, systematically examining viral seropositivity for HSV (herpes simplex virus), HZ (herpes zoster), HBV (hepatitis B virus), HIV (human immunodeficiency virus), and HCV (hepatitis C virus) through ELISA testing. The findings revealed notable active or recent viral infection rates: 8.9% HSV positivity, 2.2% HZ antibody detection, 4.4% HCV positivity, and 4.4% HIV positivity. The research can contribute to current knowledge gaps, broaden the knowledge regarding the relationship between psoriasis and viral infection, and assess resistance, as it can mediate the interaction. The results can lead to improved diagnosis, treatment, and patient care options. This study emphasizes the importance of thorough viral testing for psoriasis patients, as well as focused therapeutic regimens that take into account viral co-infections. It elucidates the complex networks of biological relationships between immune factors, contributes information that is critical to our understanding of the multifactorial etiology of psoriasis, and concludes with a strong argument for investigating the mechanisms of viral involvement in this chronic-relapsing inflammatory disease. Full article

Background: Hepatocellular carcinoma (HCC) remains a significant global health burden, particularly among vulnerable populations. This retrospective study investigates trends in HCC incidence and age at diagnosis within an urban medical center population, focusing on the impact of hepatitis C virus (HCV) treatment and racial disparities. Methods: The study includes 484 patients diagnosed with HCC between 2000 and 2023. Results: A significant decline in HCC incidence was observed with a peak in incidences between 2015 and 2017 (p < 0.02). The increase and subsequent decline were driven by a decline in HCV-related cases, particularly among the African American (AA) population. This trend was not seen for patients with other risk factors for HCC. An increase in age at diagnosis in HCV patients but not other risk patients was observed in AA (62 vs. 69 years p = 0.001) but not non-AA patients (66 vs. 67 p = 0.16). This increase in age for AA HCV patients could be due to an aging population, changing risk factor profiles, and/or limitations in surveillance and early detection of HCC. Conclusions: This study highlights the critical role of HCV treatment in reducing HCC incidence, particularly within the AA population. These findings emphasize the need for sustained efforts in surveillance, early detection, and targeted prevention strategies to address the evolving epidemiology of HCC and improve outcomes across all populations. Full article

Background: Transarterial chemoembolization (TACE) is the standard treatment for patients with intermediate-stage hepatocellular carcinoma (HCC); however, its survival benefits remain unsatisfactory. In this systematic review, we aimed to compare the clinical outcomes of tyrosine kinase inhibitors (TKIs) combined with TACE and TACE alone in patients with intermediate-stage HCC. Methods: A systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. Randomized controlled trials (RCTs) comparing TACE plus TKIs with TACE alone in patients with HCC were retrieved from PubMed, Embase, and the Cochrane Library. The primary outcomes included overall survival (OS) and progression-free survival (PFS), reported as hazard ratios (HRs) with 95% confidence intervals (CIs). Secondary outcomes included the overall response rate (ORR) and disease control rate (DCR), which were analyzed using risk ratios (RRs). Heterogeneity was assessed using the I² statistic. Results: Fourteen RCTs were included in this meta-analysis. Compared to TACE alone, TACE plus TKIs significantly improved PFS (HR = 0.74, 95% CI: 0.59–0.93, p = 0.01, I² = 87%) and the ORR (RR = 1.29, 95% CI: 1.11–1.51, p = 0.001), but not OS (HR = 0.84, 95% CI: 0.69–1.03, p = 0.10, I² = 65%) and the DCR (RR = 1.05, 95% CI: 0.99–1.11, p = 0.08). Subgroup analysis showed that TACE plus TKIs significantly increased OS in patients with hepatitis B virus (HBV) infection (HR = 0.67, 95% CI: 0.51–0.88), but not in those with hepatitis C virus (HCV) infection or those without HBV and HCV infection. Moreover, patients with HBV infection, male patients, and those with a good functional status (ECOG performance status of 0) had better PFS than others. Conclusions: Compared with TACE alone, TACE combined with TKIs can significantly improve PFS and the ORR in patients with intermediate-stage HCC. Furthermore, combination treatment can significantly improve OS in patients with HBV infection, but not in patients with HCV infection. Further research is required to optimize patient selection and treatment strategies. Full article

Background: Hepatitis C virus (HCV) remains a significant public health concern in Thailand, with genotype-specific, drug-dependent variations influencing treatment response and disease progression. Despite the availability of pan-genotypic direct-acting antivirals (DAAs), genotype surveillance remains essential for optimizing national elimination strategies. This study thus aims to characterize the molecular distribution of HCV genotypes in northern Thailand. Methods: We conducted a retrospective molecular epidemiological study on 1737 HCV-infected patients who attended the Clinical Microbiology Service Unit (CMSU) Laboratory, Faculty of Associated Medical Sciences, Chiang Mai University between April 2016 and June 2024. HCV genotyping was performed using Sanger sequencing and reverse hybridization line probe assay (LiPA). Results: Genotype 3 was the most prevalent (36.6%), followed by genotype 1 (35.8%) and genotype 6 (27.2%). Subtype 3a (27.2%) predominated, along with 1a (22.1%), 1b (12.6%), and genotype 6 subtypes including 6c to 6l (13.5%) and 6n (6.6%). Males had a higher prevalence of genotype 1, while genotype 3 was more common among females. Temporal analysis revealed a relative increase in genotype 6 prevalence since 2021. Genotype 6 also exhibited significantly higher median viral loads compared to genotypes 1 and 3 (p < 0.0001). Conclusions: This study provides updated evidence on the shifting distribution of HCV genotypes in northern Thailand, particularly the increasing prevalence of genotype 6. These findings underscore the importance of continued molecular surveillance to guide genotype-specific treatment strategies and support Thailand’s 2030 HCV elimination goals. Full article

On 11 March 2020, the World Health Organisation (WHO) declared a global pandemic caused by the SARS-CoV-2 coronavirus that earlier in February 2020 the WHO had named COVID-19 (coronavirus disease 2019). There were neither drugs nor vaccines that were known to be effective against the virus, stimulating an urgent worldwide search for treatments. An evaluation of existing drugs by ‘repurposing’ was initiated followed by a transition to de novo drug discovery. Repurposing of an already approved drug may accelerate the introduction of that drug into clinical use by circumventing early, including preclinical studies otherwise essential for a de novo drug and reducing development costs. Early in the pandemic three drugs were identified as repurposing candidates for the treatment of COVID-19: (i) hydroxychloroquine, an anti-malarial also used to treat rheumatoid arthritis and lupus; (ii) ivermectin, an antiparasitic approved for both human and veterinary use; (iii) remdesivir, an anti-viral originally developed to treat hepatitis C. The scientific evidence, both for and against the efficacy of these three drugs as treatments for COVID-19, vied with public demand and politicization as unqualified opinions clashed with evidence-based medicine. To quote Hippocrates, “There are in fact two things, science and opinion; the former begets knowledge, the latter ignorance”. Full article

Cryoglobulinemia is a rare disorder characterized by the presence of abnormal proteins (cryoglobulins) in the blood that precipitate at low temperatures. It presents with a wide clinical spectrum, from mild symptoms to severe, life-threatening disease. In mixed cryoglobulinemia (MC), vascular damage results from immune complexes—typically monoclonal IgM with rheumatoid factor activity and polyclonal IgG (Type II), or polyclonal/oligoclonal IgM and IgG (Type III). These complexes can obstruct small blood vessels, leading to ischemia and leukocytoclastic vasculitis. Renal involvement occurs in about 30% of MC patients and it is a manifestation with poor prognosis. Nowadays, types II and III MC are the most common forms, often linked to autoimmune diseases like Sjögren’s syndrome and systemic lupus erythematosus, or to viral infections such as hepatitis B or persisting despite hepatitis C eradication. This review explores renal involvement in MC, offering a comprehensive perspective on current knowledge, including recent advances in pathophysiological understanding, evolving diagnostic strategies, and novel therapeutic approaches. In this context, “perspectives” refers to the growing recognition of the shifting epidemiology of MC—particularly the changing etiological landscape following hepatitis C virus eradication—as well as the integration of emerging clinical and pathological entities such as cryofibrinogenemia and monoclonal gammopathy of renal significance into diagnostic and management frameworks. Furthermore, the review highlights current therapeutic strategies recognized as most effective, emphasizing the importance of a multidisciplinary and multimodal approach that combines etiological treatment, B-cell–targeted therapy (notably rituximab), plasma exchange in selected cases, and comprehensive supportive care for renal and systemic complications. Moreover, the landscape of management could be enriched in future years, since clinical trials are ongoing to explore novel therapies for refractory or relapsing cases of MC with renal involvement. Full article

Hepatitis B virus (HBV) infection is one of the most dangerous viral diseases, with innate immunity representing the first line of defense against the virus. In this branch of the immune system, neutrophils are considered key cellular mediators. To better understand the implication of neutrophils in the distinct stages of the disease, HBV-infected patients were enrolled in this study and categorized into three groups: patients with acute infection, chronic infection under treatment, and at early cirrhotic stage. To elucidate the role of inflammatory mediators and cellular mechanisms of neutrophilic origin in the course of the infection, both ex vivo and in vitro studies were performed. Increased levels of C-C motif chemokine ligand 2 (CCL2), interleukin (IL)-18, IL-33, and citrullinated histone H3 (CitH3)—an accurate marker of neutrophil extracellular traps (NETs)—were detected in the circulation of patients with acute infection or early cirrhosis. In parallel, sera from the aforementioned patient groups induced the formation of IL-1b-bearing NETs in neutrophils from healthy individuals. These inflammatory NETs affected primary fibroblasts towards acquiring a pro-fibrotic phenotype. These results suggest that NETs could be regarded as mediators in hepatitis B manifestations, while their therapeutic targeting could enhance the management of early-stage cirrhotic patients. Full article

Backgrounds: Direct-acting antiviral (DAA) therapy, which achieves a high sustained virological response (SVR) rate, has been established as a standard treatment for patients with hepatitis C virus (HCV) infection. However, the risk factors for postoperative recurrence in patients with HCV-related hepatocellular carcinoma (HCC) detected after the achievement of an SVR by DAAs are unknown. Methods: The clinical records of 95 patients with initial HCV-related HCC detected after DAA-SVR achievement, who underwent liver resection between September 2014 and December 2020, were retrospectively reviewed. Patients with major vascular invasion and/or SVR achievement induced by interferon-based therapy were excluded. In this study, the patients were divided into two groups according to their alcohol intake status: without alcohol abuse (<80 g of ethanol each day for at least 5 years, n = 85) and with (continuous) alcohol abuse (n = 10). The risk factors for recurrence after liver resection were investigated, with special reference to the alcohol intake status. Results: The 3- and 5-year disease-free survival (DFS) rates after liver resection were 68.7% and 55.3%, respectively. Univariate and multivariate analyses identified alcohol abuse [hazard ratio (HR) 3.36, p = 0.004] and tumor size (HR 2.53, p = 0.010) as independent risk factors for postoperative recurrence. The 3- and 5-year postoperative DFS rates were 72.2% and 61.5% for patients without alcohol abuse and 40.0% and 13.3% for those with alcohol abuse (p = 0.001). Conclusions: Continuous alcohol abuse is a risk factor for recurrence after surgery of HCC detected after the achievement of DAA-SVR. Full article