Search Results (1,158)

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

The life cycle of the hepatitis C virus (HCV) is closely linked to lipid metabolism. Recently, the stress defence transcription factor, nuclear factor erythroid 2 related factor-1 (Nrf1), has been described as a cholesterol sensor that protects the liver from excess cholesterol. Nrf1, like its homologue Nrf2, further responds to oxidative stress by binding with small Maf proteins (sMaf) to the promotor antioxidant response element (ARE). Given these facts, investigating the crosstalk between Nrf1 and HCV was a logical next step. In HCV-replicating cells, we observed reduced levels of Nrf1. Furthermore, activation of Nrf1-dependent target genes is impaired due to sMaf sequestration in replicase complexes. This results in a shortage of sMaf proteins in the nucleus, trapping Nrf1 at the replicase complexes and further limiting its function. Weakened Nrf1 activity contributes to impaired cholesterol removal, which occurs alongside an elevated intracellular cholesterol level and inhibited LXRα promoter activation. Furthermore, inhibition of Nrf1 activity correlated with a kinome profile characteristic of steatosis and enhanced inflammation—factors contributing to HCV pathogenesis. Our results indicate that activation of Nrf1-dependent target genes is impaired in HCV-positive cells. This, in turn, favours viral morphogenesis, as evidenced by enhanced replication and increased production of viral progeny. 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

Hepatitis C is an infectious liver disease which contributes to an estimated 400,000 deaths each year. The disease is caused by the hepatitis C virus (HCV) and is spread by direct blood contact between infected and susceptible individuals. While the magnitude of its impact on human populations has prompted a growing body of scientific work, the current epidemiological models of HCV transmission among injecting drug users treat risk behaviors as fixed parameters rather than as outcomes of a dynamic, decision-making process. Our study addresses this gap by constructing a game-theoretic model to investigate the implications of voluntary participation in clean needle exchange programs on the spread of HCV among this high-risk population. Individual drug users weigh the (perceived) cost of clean equipment usage relative to the (perceived) cost of infection, as well as the strategies adopted by the rest of the population, and look for a selfishly optimal level of protection. We find that the spread of HCV in this population can theoretically be eliminated if individuals use sterile equipment approximately two-thirds of the time. Achieving this level of compliance, however, requires that the real and perceived costs of obtaining sterile equipment are essentially zero. Our study demonstrates a robust method for integrating game theory with epidemiological models to analyze voluntary health interventions. It provides a quantitative justification for public health policies that eliminate all barriers—both monetary and social—to comprehensive harm-reduction services. 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

This study aimed to identify and synthesize the success metrics used to assess hepatitis C elimination among people who inject drugs (PWID) through harm reduction strategies. A scoping review was performed by searching across three databases to identify systematic reviews that discussed hepatitis C in PWID within the context of harm reduction. The studies were then analyzed for success metrics used to describe hepatitis C in PWID. The indicators used were prevalence, incidence, screening, treatment uptake, treatment completion, and sustained virologic response. A total of fourteen systematic reviews were included. The most frequently reported indicators were prevalence and incidence, addressed in eight/seven systematic reviews, respectively. In contrast, screening, treatment uptake, and treatment completion were less commonly reported, with only two reviews addressing screening and treatment uptake, and a single review reporting treatment completion. Similarly, sustained virologic response (SVR) was reported in only two systematic reviews. Seven additional indicators were reported. Prevalence and incidence are the dominantly used HCV indicators, while others are often neglected. Inconsistencies in measurements and reporting can be found for all indicators. This study reports a gap regarding indicators beyond prevalence and incidence, inconsistent measurement approaches, and a lack of standardized frameworks. 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