Treatment initiation rates of patients with positive anti-hepatitis C virus results in tertiary hospitals in Turkey.

INTRODUCTION: The aim of this national, multicenter, cross-sectional, retrospective chart review study was to determine the proportion of patients in Turkey who received hepatitis C virus (HCV) treatment after receiving positive anti-HCV results during HCV screening. METHODOLOGY: Data related to patients' demographics, laboratory results, time interval from obtaining a positive anti-HCV result to treatment initiation, specialty of the physician requesting anti-HCV screening, and type of hospital were analyzed. RESULTS: Among 1,000 patients who received a positive anti-HCV result, 50.3% were male and 78.5% were screened for HCV-RNA. Among HCV-RNA screened patients, 54.8% (n = 430) had a positive result. Among patients who tested positive for HCV-RNA, 72.8% received HCV treatment in line with their positive anti-HCV results. The median time from obtaining a positive anti-HCV result to initiation of HCV treatment was 91.0 days (interquartile range 42.0 to 178.5). Non-surgical branches requested HCV-RNA testing more frequently than surgical branches (p < 0.001). The rate of access to HCV treatment was higher among patients screened in university hospitals than among patients screened in training and research hospitals (p < 0.001). CONCLUSIONS: Our results indicate a higher rate of treatment initiation among patients with HCV infection than is described in the published literature. Furthermore, the time from screening to treatment initiation was considerably shorter compared with other international studies. However, since HCV-RNA testing was not requested in a significant portion of patients with a positive anti-HCV test result, there might be a large patient population with HCV who do not receive treatment.

Distribution and genotyping of hepatitis C virus (HCV) infection in Gansu province, China.

INTRODUCTION: The distribution of common subtypes of hepatitis C virus (HCV) in Gansu province were analyzed. This information provided a theoretical basis for the selection of appropriate antiviral treatment regimens. METHODOLOGY: We collected data on HCV antibody screening tests from 421,802 outpatients and inpatients at the Second Clinical Hospital of Lanzhou University from January 2018 to June 2022. Ribonucleic acid (RNA) viral load, HCV genotypes, and HCV quantification were analyzed retrospectively. The results of HCV positive detection rate, copy number, and genotype distribution were statistically analysed using SPSS 26.0. RESULTS: A total of 421,802 HCV antibody screenings were performed resulting in 4,558 positive cases (1.081%). In addition, 2,345 cases (1.302%) were positive with quantitative HCV antibodies in 180,157 outpatients and inpatients. Quantitative HCV virus RNA was further measured in 2592 outpatients and inpatients. There were 825 positive cases for HCV, with a positivity rate of 31.83%. High-sensitivity quantification of HCV-RNA was performed in 6538 patients, among which 1336 were HCV-RNA positive infections (positivity rate of 20.43%). Among the 1484 genotype tests, 4 genotypes and 10 subtypes were detected, including 4a, 1b, 2a, 2b, 3a, 3b, 6a, 6n, 1b/2a, and 2a/6a, with the majority of results from 2a (51.89%) and 1b (42.72%). CONCLUSIONS: The most prevalent genetic subtype in HCV-positive patients in Gansu was 2a, followed by 1b. In addition, 8 genotype subtypes appeared: 1a, 2b, 3a, 3b, 6a, 6n, 1b/2a and 2a/6a. Understanding the distribution of HCV genes in Gansu province is of significance for the optimization of virus treatment.

Establishment and methodological evaluation of a chemiluminescence assay for detection of anti-envelope protein (E1, E2) antibodies in the serum of hepatitis C virus-infected patients.

BACKGROUND: To establish a chemiluminescence method for detecting anti-E1 and anti-E2 antibodies in the serum of patients with hepatitis C virus (HCV) infection. METHODS: The microplate was coated with recombinant envelope proteins E1 and E2 by indirect method, respectively, and the kits for detecting anti-E1 and anti-E2 antibodies were prepared. The methodological indexes were evaluated. RESULTS: The methodological indexes of the kits were as follows: precision test (the variation coefficient of anti-E1 antibody 6.71%-8.95% for within run and 9.91%-12.16% for between run, the variation coefficient of anti-E2 antibody 6.06%-8.44% for within run and 10.77%-13.98% for between run, respectively). The blank limit and detection limit were 1.18 RLIR and 3.16 RLIR for the anti-E1 antibody, and 1.26 RLIR and 3.32 RLIR for the anti-E2 antibody, respectively. The correlation coefficients (r) of anti-E1 and anti-E2 were 0.9963 and 0.9828, the analysis and measurement ranges (AMR) were 1.66-41.28 RLIR and 1.55-19.46 RLIR, and the average recovery was 96.4% and 93.7%, respectively. The rheumatoid factor and other positive serum samples had no interference or cross-reaction to the test, and the kits were stable within 15 months. The positive rates of anti-E1 and anti-E2 antibodies in 45 patients with HCV infection were 35.6% (16/45) and 44.4% (20/45), respectively. CONCLUSIONS: The kits for detecting anti-E1 and anti-E2 meet the requirements of methodology, and can be used in screening diagnosis, disease monitoring, prognosis evaluation, disease mechanism, and epidemiological studies of HCV infection. The HCV envelope proteins E1 and E2 have an immune response in HCV-infected patients.

[HCV antigen detection method and clinical application].

Hepatitis C is distributed worldwide and possesses a hidden characteristic. The traditional methods of screening and diagnosis of hepatitis C infection commonly used in clinics are based on anti-HCV antibody and HCV RNA detection. Advances in HCV antigen detection technologies can apparently reduce the window period for anti-HCV antibodies, providing new clinical evidence for the early detection, diagnosis, and treatment of HCV infection. This article is a current review of HCV antigen detection methodologies, clinical applications, and detection strategies.

Hospital-based screening outperforms primary care screening as a means of achieving hepatitis C virus micro-elimination.

AIM: To assess the respective performances of a HCV screening program in a hospital setting and a HCV screening model applied concomitantly in a primary care centre. METHODS: Adult patients consecutively admitted to hospital for ambulatory surgery were screened for anti-HCV antibodies (hospital screening cohort, HPSC), as were patients receiving blood tests for medical reasons in a primary care centre (primary care screening cohort, PCSC). Serum anti-HCV and HCV RNA levels were tested by ELISA and real-time PCR, respectively. RESULTS: Seroprevalence of HCV infection was 2.2 % in the HPSC and 1.4 % in the PCSC (p = 0.044). All viraemic patients (0.2 % in HPSC and 0.1 % in PCSC) were treated with direct-acting antivirals and 85.7 % experienced a sustained virological response. CONCLUSIONS: Hospital-based HCV screening outperformed primary care-centered screening, significantly increasing HCV case findings.

Validation of dried blood spots for capturing hepatitis C virus diversity for genomic surveillance.

Dried blood spots (DBS) have emerged as a promising alternative to traditional venous blood for hepatitis C virus (HCV) testing. However, their capacity to accurately reflect the genetic diversity of HCV remains poorly understood. We employed deep sequencing and advanced phylogenetic analyses on paired plasma and DBS samples from two common subtypes to evaluate the suitability of DBS for genomic surveillance. Results demonstrated that DBS captured equivalent viral diversity compared to plasma with no phylogenetic discordance observed. The ability of DBS to accurately reflect the profile of viral genetic diversity suggests it may be a promising avenue for future surveillance efforts to curb HCV outbreaks.

Prevalence of hepatitis B and C infection and linkage to care among patients with Non-Communicable Diseases in three rural Rwandan districts: a retrospective cross-sectional study.

INTRODUCTION: Rwanda's Hepatitis C elimination campaign has relied on mass screening campaigns. An alternative "micro-elimination" strategy focused on specific populations, such as non-communicable disease (NCD) patients, could be a more efficient approach to identifying patients and linking them to care. METHODS: This retrospective cross-sectional study used routine data collected during a targeted screening campaign among NCD patients in Kirehe, Kayonza, and Burera districts of Rwanda and patients receiving oncology services from the Butaro District Hospital. The campaign used rapid diagnostic tests to screen for Hepatitis B surface antigen (HBsAg) and Hepatitis C antibody (anti-HCV). We reported prevalences and 95% confidence intervals for HBsAg and anti-HCV, assessed for associations between patients' clinical programs and hepatitis B and C, and reported cascade of care for the two diseases. RESULTS: Out of 7,603 NCD patients, 3398 (45.9%) self-reported a prior hepatitis screening. Prevalence of HBsAg was 2.0% (95% CI: 1.7%-2.3%) and anti-HCV was 6.7% (95% CI: 6.2%-7.3%). The prevalence of HBsAg was significantly higher among patients < 40 years (2.4%). Increased age was significantly associated with anti-HCV (12.0% among patients ≥ 70 years). Of the 148 individuals who screened positive for HbsAg, 123 had viral load results returned, 101 had detectable viral loads (median viral load: 451 UI/mL), and 12 were linked to care. Of the 507 individuals who screened positive for anti-HCV, 468 had their viral load results returned (median viral load: 1,130,000 UI/mL), 304 had detectable viral loads, and 230 were linked to care. CONCLUSION: Anti-HCV prevalence among Rwandan patients with NCD was high, likely due to their older age. NCD-HCV co-infected patients had high HCV viral loads and may be at risk of poor outcomes from hepatitis C. Hepatitis C micro-elimination campaigns among NCD patients are a feasible and acceptable strategy to enhance case detection in this high-prevalence population with elevated viral loads and may support linkage to care for hepatitis C among elderly populations.

The best anti-HCV S/Co values for reflecting HCV infection in a university hospital in the eastern part of Turkey.

INTRODUCTION: The measurement of hepatitis C virus (HCV) RNA is a test that requires high cost, advanced technique, and qualified personnel. Diagnosis and treatment of patients may be delayed due to the high rate of false-positive results. This study aims to predict true antibody positivity and viremia by determining the most appropriate anti-HCV signal-to-cutoff (S/Co) value reflecting HCV infection. METHODOLOGY: The presence of anti-HCV antibodies and HCV RNA levels were examined in 72341 people who applied to the Mengücek Gazi Training and Research Hospital between January 2018 and December 2020. The anti-HCV levels were determined by using the Abbot Architect i2000 SR device (Abbot Diagnostics, Chicago, IL, USA). The levels of HCV RNA were determined in the COBAS AmpliPrep/COBAS, TaqMan 48 (Roche, Diagnostics, Pleasanton, USA) devices using serum samples from patients. Our study is a retrospective and methodological study. RESULTS: Of the 150 patients with anti-HCV antibodies, 50 (33.3%) were HCV RNA positive, and 100 (66.7%) were HCV RNA negative. Anti-HCV levels of HCV RNA-positive patients were statistically higher than HCV RNA-negative patients. The most appropriate anti-HCV S/Co value for diagnosing hepatitis C patients was 15.4. The sensitivity of this value was 72%, specificity 88%, positive predictive value (PPV) 73.5%, and negative predictive value (NPV) 86.1%. Receiver operating characteristic (ROC) curve was significantly higher than 0.5 (95% confidence interval 0.938-0.827). CONCLUSIONS: Correct approaches can be applied in the diagnosis of HCV infection using the anti-HCV S/Co value found in our study.

Characterization of antibody-dependent cellular phagocytosis in patients infected with hepatitis C virus with different clinical outcomes.

Early neutralizing antibodies against hepatitis C virus (HCV) and CD8 + T cell effector responses can lead to viral clearance. However, these functions alone are not sufficient to protect patients against HCV infection, thus undefined additional antiviral immune mechanisms are required. In recent years, Fc-receptor-dependent antibody effector functions, particularly, antibody-dependent cellular phagocytosis (ADCP) were shown to offer immune protection against several RNA viruses. However, its development and clinical role in patients with HCV infection remain unknown. In this study, we found that patients with chronic GT1a or GT3a HCV infection had significantly higher concentrations of anti-envelope 2 (E2) antibodies, predominantly IgG1 subclass, than patients that cleared the viruses while the latter had antibodies with higher affinities. 97% of the patients with HCV had measurable ADCP of whom patients with chronic disease showed significantly higher ADCP than those who naturally cleared the virus. Epitope mapping studies showed that patients with antibodies that target antigenic domains on the HCV E2 protein that are known to associate with neutralization function are also strongly associated with ADCP, suggesting antibodies with overlapping/dual functions. Correlation studies showed that ADCP significantly correlated with plasma anti-E2 antibody levels and neutralization function regardless of clinical outcome and genotype of infecting virus, while a significant correlation between ADCP and affinity was only evident in patients that cleared the virus. These results suggest ADCP was mostly driven by antibody titer in patients with chronic disease while maintained in clearers due to the quality (affinity) of their anti-E2 antibodies despite having lower antibody titers.

Evidence for the elimination of viral hepatitis B and C in Egypt: Results of a nationwide survey in 2022.

INTRODUCTION: Viral hepatitis C (HCV) and B (HBV) were at the top of Egypt's most significant public health challenges, with an estimated 14.7% of its population having antibodies to HCV in 2008. Egypt issued an ambitious action plan in 2014 to eliminate viral hepatitis through strengthening infection control and improving patient care. In 2018, an extensive HCV mass screening campaign was conducted for the entire country's population with treating more than 4 million patients with antivirals. This study aimed to evaluate the current prevalence of viral hepatitis in Egypt after all these efforts. METHODS: A cross-sectional household cluster survey was conducted in all 27 Egyptian governorates to obtain a representative sample of Egypt's population. Subjects aged 1-70 years were interviewed using a standardised questionnaire that included demographics, viral hepatitis knowledge, previous infection and risk factors data. Laboratory testing was performed for all subjects for anti-HCV and HBsAg using chemiluminescence. Subjects positive for anti-HCV were further tested for HCV-RNA by RT-PCR. Prevalence rates were calculated by demographic groups and compared to the demographic health survey 2015 results. RESULTS: Of 20 881 subjects interviewed, 48.8% were males, 20.2% were children <15 years of age, and 53.7% were residents of rural areas. Of all subjects, 92 (0.4%) were HCV-infected, 1577 (7.6%) were anti-HCV positive and 177 (0.8%) were HBV-chronically infected, including one patient who had mixed HBV and HCV current infection. The prevalence of HCV-current and HBV chronic infections decreased by 93% and 20%, respectively, compared to 2015. CONCLUSIONS: Egypt achieved the elimination of the viral hepatitis goal. To maintain low rates of viral hepatitis, community health education, in addition to maintaining infection control and blood safety programs, is essential.

Hepatitis C virus E1 recruits high-density lipoprotein to support infectivity and evade antibody recognition.

Hepatitis C virus (HCV) is a member of the Flaviviridae family; however, unlike other family members, the HCV virion has an unusually high lipid content. HCV has two envelope glycoproteins, E1 and E2. E2 contributes to receptor binding, cell membrane attachment, and immune evasion. In contrast, the functions of E1 are poorly characterized due, in part, to challenges in producing the protein. This manuscript describes the expression and purification of a soluble E1 ectodomain (eE1) that is recognized by conformational, human monoclonal antibodies. eE1 forms a complex with apolipoproteins AI and AII, cholesterol, and phospholipids by recruiting high-density lipoprotein (HDL) from the extracellular media. We show that HDL binding is a function specific to eE1 and HDL hinders recognition of E1 by a neutralizing monoclonal antibody. Either low-density lipoprotein or HDL increases the production and infectivity of cell culture-produced HCV, but E1 preferentially selects HDL, influencing both viral life cycle and antibody evasion.IMPORTANCEHepatitis C virus (HCV) infection is a significant burden on human health, but vaccine candidates have yet to provide broad protection against this infection. We have developed a method to produce high quantities of soluble E1 or E2, the viral proteins located on the surface of HCV. HCV has an unusually high lipid content due to the recruitment of apolipoproteins. We found that E1 (and not E2) preferentially recruits host high-density lipoprotein (HDL) extracellularly. This recruitment of HDL by E1 prevents binding of E1 by a neutralizing antibody and furthermore prevents antibody-mediated neutralization of the virus. By comparison, low-density lipoprotein does not protect the virus from antibody-mediated neutralization. Our findings provide mechanistic insight into apolipoprotein recruitment, which may be critical for vaccine development.

Neutralizing antibodies evolve to exploit vulnerable sites in the HCV envelope glycoprotein E2 and mediate spontaneous clearance of infection.

Individuals who clear primary hepatitis C virus (HCV) infections clear subsequent reinfections more than 80% of the time, but the mechanisms are poorly defined. Here, we used HCV variants and plasma from individuals with repeated clearance to characterize longitudinal changes in envelope glycoprotein E2 sequences, function, and neutralizing antibody (NAb) resistance. Clearance of infection was associated with early selection of viruses with NAb resistance substitutions that also reduced E2 binding to CD81, the primary HCV receptor. Later, peri-clearance plasma samples regained neutralizing capacity against these variants. We identified a subset of broadly NAbs (bNAbs) for which these loss-of-fitness substitutions conferred resistance to unmutated bNAb ancestors but increased sensitivity to mature bNAbs. These data demonstrate a mechanism by which neutralizing antibodies contribute to repeated immune-mediated HCV clearance, identifying specific bNAbs that exploit fundamental vulnerabilities in E2. The induction of bNAbs with these specificities should be a goal of HCV vaccine development.

Glycylglycine promotes the solubility and antigenic utility of recombinant HCV structural proteins in a point-of-care immunoassay for detection of active viremia.

BACKGROUND: Although E. coli is generally a well-opted platform for the overproduction of recombinant antigens as heterologous proteins, the optimization of expression conditions to maximize the yield of functional proteins remains empirical. Herein, we developed an optimized E. coli (BL21)-based system for the overproduction of soluble immunoreactive HCV core/envelope proteins that were utilized to establish a novel immunoassay for discrimination of active HCV infection. METHODS: The core/E1-E2 genes were amplified and expressed in E. coli BL21 (DE3) in the absence/presence of glycylglycine. The antigenic performance of soluble proteins was assessed against 63 HCV-seronegative (Ab-) sera that included normal and interferent sera (HBV and/or chronic renal failure), and 383 HCV-seropositive (Ab+) samples that included viremic (chronic/relapsers) and recovered patients' sera. The color intensity (OD450) and S/Co values were estimated. RESULTS: The integration of 0.1-0.4M glycylglycine in the growth media significantly enhanced the solubility/yield of recombinant core and envelope proteins by ~ 225 and 242 fold, respectively. This was reflected in their immunoreactivity and antigenic performance in the developed immunoassay, where the soluble core/E1/E2 antigen mixture showed 100% accuracy in identifying HCV viremic sera with a viral RNA load as low as 3800 IU/mL, without cross-reactivity against normal/interferent HCV-Ab-sera. The ideal S/Co threshold predicting active viremia (> 2.75) showed an AUC value of 0.9362 (95% CI: 0.9132 to 0.9593), with 87.64, 91.23% sensitivity and specificity, and 94.14, 82.11% positive and negative predictive values, respectively. The different panels of samples assayed with our EIA showed a good concordance with the viral loads and also significant correlations with the golden standards of HCV diagnosis in viremic patients. The performance of the EIA was not affected by the immunocompromised conditions or HBV co-infection. CONCLUSION: The applicability of the proposed platform would extend beyond the reported approach, where glycylglycine, low inducer concentration and post-induction temperature, combined with the moderately-strong constitutive promoter enables the stable production of soluble/active proteins, even those with reported toxicity. Also, the newly developed immunoassay provides a cost-effective point-of-care diagnostic tool for active HCV viremia that could be useful in resource-limited settings.

Seroprevalence of hepatitis B, C, and D and associated factors in the semi-isolated Yanomami Amazonian indigenous community.

BACKGROUND: Viral hepatitis is a significant health concern among indigenous population in the Americas. In Brazil, reports find high endemicity of HBV and HDV infections has been reported in several indigenous groups. However, few studies have documented the prevalence of HBV, HCV and HDV in the Yanomami. In this study, the prevalence of hepatitis B, C, and D serological markers and potential risk factors were investigated to provide guidance for the development of strategies aimed at reducing viral transmission in the Yanomami indigenous villages. METHODS: This cross-sectional study was carried out in March 2015 and included 430 individuals from four Yanomami villages: Alapusi (n = 78), Castanha/Ahima (n = 126), Gasolina (n = 105), and Taibrapa (n = 121). A rapid test was used for detection of HBsAg and anti-HCV and chemiluminescent immunoassay for anti-HBs, anti-HBc, and anti-HDV antibodies. RESULTS: HBsAg, anti-HBc, and anti-HBs were detected in 8.8, 45.5, and 49.4% of the participants, respectively. The estimated HBV status: current infection 9.6% (38/395); resolved infection 43.3% (171/395); vaccine immunity 20.5% (81/395), and susceptible to HBV 26.6% (105/395). Gasolina presented the lowest prevalence of HBV infection (6.5%) and the highest prevalence of vaccine immunity (26.9%). Children < 15 years old were highly susceptible to infection, as 53.1% did not have antibodies to HBV, while more than 80% of individuals over 45 years of age had been exposed to HBV. The markers for HDV were founded among 12.5% (4/32) of the HBsAg carriers. Anti-HCV was identified in all villages, with the highest prevalence in Alapusi (5.1%). Possible risk factors such as the use of piercings, tattoos, and contact with prospectors showed no statistical difference between the groups. CONCLUSIONS: Viral hepatitis B and serological markers for HCV and HDV were found to be widely distributed among the Yanomami indigenous community, while the prevalence of vaccine immunity to HBV was low. This finding reinforces the importance of promoting systematized diagnostic and vaccination strategies in indigenous communities. Our data confirm that isolated and difficult-to-reach indigenous communities lack appropriate access to diagnosis, treatment, and vaccination.

A panel of hepatitis C virus glycoproteins for the characterization of antibody responses using antibodies with diverse recognition and neutralization patterns.

A vaccine against Hepatitis C virus (HCV) is urgently needed to limit the spread of HCV. The large antigenic diversity of the HCV glycoprotein E1E2 makes it difficult to design a vaccine but also to fully understand the antibody response after infection or vaccination. Here we designed a panel of HCV pseudoparticles (HCVpps) that cover a wide range of genetically and antigenically diverse E1E2s. We validate our panel using neutralization and a binding antibody multiplex assay (BAMA). The panel of HCVpps includes E1E2 glycoproteins from acute and chronically infected cases in the Netherlands, as well as E1E2 glycoproteins from previously reported HCVs. Using eight monoclonal antibodies targeting multiple antigenic regions on E1E2, we could categorize four groups of neutralization sensitive viruses with viruses showing neutralization titers over a 100-fold range. One HCVpp (AMS0230) was extremely neutralization resistant and only neutralized by AR4-targeting antibodies. In addition, using binding antibody multiplex competition assay, we delineated mAb epitopes and their interactions. The binding and neutralization sensitivity of the HCVpps were confirmed using patient sera. At the end, eleven HCVpps with unique antibody binding and neutralization profiles were selected as the final panel for standardized HCV antibody assessments. In conclusion, this HCVpp panel can be used to evaluate antibody binding and neutralization breadth and potency as well as delineate the epitopes targeted in sera from patients or candidate vaccine trials. The HCVpp panel in combination with the established antibody competition assay present highly valuable tools for HCV vaccine development and evaluation.

Patient-centered and integrated outreach care for chronic hepatitis C patients with serious mental illness in Taiwan.

Patients with serious mental illness have a higher risk of hepatitis C virus (HCV) infection but suboptimal HCV care. The current study aimed to facilitate HCV treatment uptake by implementing an integrated outreach care model. Multidisciplinary outreach screening followed by HCV reflex testing and onsite treatment for schizophrenia patients was accomplished through the coordination of nongovernmental organizations, remote specialists, and local care providers. The objective was microelimination effectiveness, defined as the multiplication of the rates of anti-HCV antibodies screening, accurate HCV RNA diagnosis, treatment allocation, treatment completion, and sustained virological response (SVR12; no detectable HCV RNA throughout 12 weeks in the post-treatment follow-up period). A total of 1478 of the 2300 (64.3%) psychiatric patients received HCV mass screening. Seventy-three (4.9%) individuals were seropositive for anti-HCV antibodies. Of the 73 anti-HCV seropositive patients, all (100%) received HCV reflex testing, and 29 (37.7%) patients had HCV viremia. Eight patients (34.8%) had advanced liver disease, including 3 with liver cirrhosis and 2 with newly diagnosed hepatocellular carcinoma. Twenty-three of the 24 (95.8%) patients who stayed in the healthcare system received and completed 8 weeks of glecaprevir/pibrentasvir treatment and post-treatment follow-up without significant DDIs or adverse events. The SVR12 rate was 100%. The microelimination effectiveness in the current study was 61.6%. Individuals with serious mental illness are underserved and suffer from diagnostic delays. This patient-centered and integrated outreach program facilitated HCV care in this marginalized population.

Validation of dried blood spot for serological diagnosis of Hepatitis B and C: a multicentric study.

The present study aimed to determine diagnostic performance of dried blood spot (DBS) for the detection of Hepatitis B surface antigen (HBsAg) and Hepatitis C virus antibodies (anti-HCV) using CLIA at 3 different laboratories across India. DBS can serve as a simple and convenient alternative to plasma/serum for HBsAg detection. However for anti-HCV, site-specific validation of the assay is warranted.

Hepatitis C virus modified sE2F442NYT as an antigen in candidate vaccine facilitates human immune cell activation.

The rational selection of hepatitis C virus (HCV) vaccine antigen will aid in the prevention of future chronic liver disease burden and associated healthcare costs. We have previously shown that HCV E2 glycoprotein is not highly immunogenic, and the modification of E2 reduced CD81 binding and displayed altered cytokine and protective immune responses in vitro and in a surrogate mouse model. Here, we compared the influence of a parental and a modified sE2F442NYT glycoprotein region from HCV genotype 1a for the activation of peripheral blood mononuclear cell (PBMC)-derived dendritic cells (DCs), CD4+T cells, and B cells. Modified sE2F442NYT, when incubated with DCs, induced a higher number of CD86-positive cells. The sE2F442NYT or parental sE2 encapsulated as mRNA-lipid nanoparticle (sE2F442NYT mRNA-LNP) primed DCs co-cultured with autologous CD4+T cells did not induce CD25 or forkhead box P3 expression. PBMC-derived CD4+T cells treated with sE2F442NYT exhibited enhanced signal transducer and activator of transcription (Stat)1/Stat4 phosphorylation in response to anti-CD3/CD28 stimulation in comparison to parental sE2 treatment and facilitated isotype switching in B cells, leading to the generation of a broader subclass of antibodies. Cells treated with modified sE2F442NYT displayed an increase in activated Stat3 and extracellular signal-regulated kinase (ERK). Likewise, PBMC-derived naïve B cells upon in vitro stimulation with sE2F442NYT induced an increased proliferation, Stat3 and ERK activation, and protein kinase B (Akt) suppression. Thus, the modified sE2F442NYT antigen from HCV facilitates improved DC, CD4+T, and B cell activation compared to parental sE2 to better induce a robust protective immune response, supporting its selection as an HCV candidate vaccine antigen for preclinical and clinical HCV vaccine trials.IMPORTANCEThe nature of an enhanced immune response induced by sE2F442NYT will help in the selection of a broad cross-protective antigen from hepatitis C virus genotypes, and the inclusion of relatively conserved sE1 with sE2F442NYT may further strengthen the efficacy of the candidate vaccine in evaluating it for human use.

Combining cross-sectional survey and register data improved the estimate of hepatitis C prevalence among patients attending a psychiatric emergency department in Denmark.

BACKGROUND: The prevalence of hepatitis C (HCV) among psychiatric patients is elevated compared to the background population in many studies, but the prevalence among Danish psychiatric patients is unknown. The aim of the study was to determine the HCV prevalence and the proportion of the psychiatric patient population that remains to be diagnosed and treated in a Danish setting. METHODS: During a 5-month period, patients attending the psychiatric emergency room in Vejle, Denmark, were offered point-of-care anti-HCV testing. Previous hepatitis C tests for all patients attending the Psychiatric Department in the study period were extracted from the national laboratory database (DANVIR). We combined the survey and register data in a capture-recapture estimate of undiagnosed patients with HCV. RESULTS: During the study 24.9% (589 of 2364) patients seen at the psychiatric department attended the emergency room. The prevalence of anti-HCV among those tested in the emergency room was 1.6%. The laboratory register identified 595/2364 patients previously tested for anti-HCV with a positive prevalence of 6.1%. The undiagnosed anti-HCV positives among the 1483 never tested was estimated to 1.1%. Thus the total estimated prevalence of anti-HCV was 2.3% (54/2364, 95% CI 1.7%-3.0%) in the population, of whom 70.4% had been diagnosed, and 72.2% of diagnosed patients had received treatment or cleared HCV. CONCLUSION: Combining survey and register data showed that the WHO target of 90% diagnosed and 80% treated was not met. To eliminate HCV in the psychiatric population, both undiagnosed and untreated patients must be targeted.

SEROEPIDEMIOLOGY OF HBV ANTIGEN AND ANTI-HCV AMONG GENERAL POPULATION IN A RURAL LOCAL IN BAUCHI STATE, NIGERIA.

Background: HBV and HCV infections are a significant public health issue in developing countries with weak healthcare systems, high poverty rates, illiteracy, low HBV immunization coverage, and low public health education. A study assessed the sero epidemiology of HBV antigen, anti- HCV markers, biochemical and heamatological indices of 559 participants in Dambam local government during hepatitis day. A structured questionnaire was administered to assess demographic information and risk factors. Rapid latex immunochromtographic kits were used for HBV, HCV, and HBV Combo serological markers, with positive and negative control included in each batch analysis. Descriptive statistics analysis was conducted on the data. Results: The 559 study participants, had a mean age of 35.5+10.9years, majority within the age- group, 18-39years 279(49.04%), female accounted for 291(52.1%) compared to male 268(47.9), educational background, tertiary 244(43.6%), married, 356(68.7%) and student were 254(45.4%). Seroprevalence of HBsAg was 10.7%, serological markers as follows, HbsAb 1.7%, HbeAg 13.3%, HbeAb 60.0% HbcAb 95.0% and Anti-HCV of 3.4%. Gender breakdown(M vs F) of HBV(13.4% vs 8.2%) and HCV(3.0% vs 3.8%). Significant association was observed in the seroprevalence of HBV and HCV with age-group, gender, marital status and occupation(<0.05). No significant difference was observed with the risk factors of HBV and HCV. Biochemical and heamatological indices showed a significant difference between seropositive and negative study participants(<0.05). Conclusion: The study's findings affirmed the endemicity of HBV infection and the increasing trend of HCV infection in Bauchi state, posing serious public health concerns. HBV serological markers suggest a low HBV immunization coverage rate and exposure of participants to the viral etiology in the community. Strengthening immunization coverage and population-based surveillance is strategic in the prevention and control of viral hepatitis in Bauchi state.