Performance of HCV Antigen Testing for the Diagnosis and Monitoring of Antiviral Treatment: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Active hepatitis C virus (HCV) infection is based on the detection of HCV RNA that it is effective but presents high cost and the need to hire trained personnel. This systematic review and meta-analysis is aimed at evaluating the diagnostic accuracy of HCV Ag testing to identify HCV cases and to monitor antiviral treatment including DAA treatment. METHODS: The studies were identified through a search in PubMed, Lilacs, and Scopus from 1990 through March 31, 2020. Cohort, cross-sectional, and randomized controlled trials were included. Two independent reviewers extracted data and assessed quality using an adapted Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Our primary outcome was to determine the accuracy of HCV Ag detection for the diagnosis, which we estimated using random-effects meta-analysis. RESULTS: Of 3,062 articles identified, 54 met our eligibility criteria. The studies described cohorts from 20 countries, including 14,286 individuals with chronic HCV individuals. Studies for ECLIA technology demonstrated highest quality compared to studies that used ELISA. The pooled sensitivity and specificity (95% CI) for HCV Ag detection of active HCV infection were 98.82% (95%CI = 98.04%; 99.30%) and 98.95% (95%CI = 97.84%; 99.49%), respectively. High concordance was found between HCV Ag testing and HCV RNA detection 89.7% and 95% to evaluate antiviral treatment. CONCLUSIONS: According to our findings, HCV Ag testing could be useful to identify HCV active cases in low-resource areas. For antiviral treatment, HCV Ag testing will be useful at the end of treatment.

IgG1 and IgG4 antibodies against Core and NS3 antigens of hepatitis C virus.

INTRODUCTION: IgG subclasses involved in the immune response to hepatitis C virus (HCV) antigens have been rarely studied. We investigated the immune response mediated by IgG1 and IgG4 antibodies against the recombinant core and NS3 antigens in patients with chronic hepatitis C. METHODS: Sixty patients infected with HCV genotype 1 without antiviral treatment and 60 healthy subjects participated in the study. Serum levels of alanine aminotransferase, HCV viremia, and the presence of cryoglobulinemia and liver fibrosis were determined. We investigated the serum IgG1 and IgG4 antibodies against recombinant HCV core and NS3 non-structural protein antigens using amplified indirect ELISA. RESULTS: Anti-core and anti-NS3 IgG1 antibodies were detected in 33/60 (55%) and 46/60 (77%) patients, respectively, whereas only two healthy control samples reacted with an antigen (NS3). Anti-core IgG4 antibodies were not detected in either group, while 30/60 (50%) patients had anti-NS3 IgG4 antibodies. Even though there were higher levels of anti-NS3 IgG4 antibodies in patients with low viremia (< 8 × 105 IU/mL), IgG1 and IgG4 antibody levels did not correlate with ALT levels, the presence of cryoglobulinemia, or degree of hepatic fibrosis. High production of anti-core and anti-NS3 IgG1 antibodies was observed in chronic hepatitis C patients. In contrast, IgG4 antibodies seemed to only be produced against the NS3 non-structural antigen and appeared to be involved in viremia control. CONCLUSIONS: IgG1 antibodies against structural and non-structural antigens can be detected in chronic hepatitis C, while IgG4 antibodies seem to be selectively stimulated by non-structural HCV proteins, such as the NS3 antigen.

IgG1 and IgG4 antibodies against core and NS3 antigens of hepatitis C virus

Abstract INTRODUCTION: IgG subclasses involved in the immune response to hepatitis C virus (HCV) antigens have been rarely studied. We investigated the immune response mediated by IgG1 and IgG4 antibodies against the recombinant core and NS3 antigens in patients with chronic hepatitis C. METHODS: Sixty patients infected with HCV genotype 1 without antiviral treatment and 60 healthy subjects participated in the study. Serum levels of alanine aminotransferase, HCV viremia, and the presence of cryoglobulinemia and liver fibrosis were determined. We investigated the serum IgG1 and IgG4 antibodies against recombinant HCV core and NS3 non-structural protein antigens using amplified indirect ELISA. RESULTS: Anti-core and anti-NS3 IgG1 antibodies were detected in 33/60 (55%) and 46/60 (77%) patients, respectively, whereas only two healthy control samples reacted with an antigen (NS3). Anti-core IgG4 antibodies were not detected in either group, while 30/60 (50%) patients had anti-NS3 IgG4 antibodies. Even though there were higher levels of anti-NS3 IgG4 antibodies in patients with low viremia (< 8 × 105 IU/mL), IgG1 and IgG4 antibody levels did not correlate with ALT levels, the presence of cryoglobulinemia, or degree of hepatic fibrosis. High production of anti-core and anti-NS3 IgG1 antibodies was observed in chronic hepatitis C patients. In contrast, IgG4 antibodies seemed to only be produced against the NS3 non-structural antigen and appeared to be involved in viremia control. CONCLUSIONS: IgG1 antibodies against structural and non-structural antigens can be detected in chronic hepatitis C, while IgG4 antibodies seem to be selectively stimulated by non-structural HCV proteins, such as the NS3 antigen.

Hepatitis C virus core antigen assay: can we think beyond convention in resource limited settings?

Hepatitis C virus infects over 15 million patients from India and 2.86 million from Brazil. Detection of anti-hepatitis C virus antibodies has limited sensitivity during acute phase: the pre-seroconversion window period. Hepatitis C virus-RNA detection techniques are used to overcome this shortfall, but are costly and unavailable widely in developing countries. Estimation of hepatitis C virus core-antigen, a protein with highly conserved sequence, by enzyme-immunoassays is an economic and simpler alternative to RNA detection. This study was conducted in Delhi, involving 300 acute and chronic liver disease patients, tested for anti-hepatitis C virus 3rd-generation ELISA, hepatitis C virus core-antigen-ELISA and hepatitis C virus-RNA reverse transcription-polymerase chain reaction. Among the acute patients, hepatitis C virus core-antigen assay could identify 13 out of 14 pre-seroconversion window period cases and 6 out of 8 seroconverted cases, with a pre-seroconversion window period sensitivity of 92.9% and specificity of 100%. In hepatitis C virus core-antigen-positive cases, the viral load was in the range of 4900 to 1.46×10(6)IU/mL, whereas in hepatitis C virus core-antigen-negative cases, the range of viral load was 100-4500IU/mL. The cost of the hepatitis C virus core-antigen-ELISA was estimated around 3-4 times lesser than the in-house reverse transcription-polymerase chain reaction and 9-10 times lesser than the United States Food and Drug Administration approved reverse transcription-polymerase chain reaction. With a good sensitivity and specificity in the acute phase of infection, hepatitis C virus core-antigen-ELISA can thus be a useful alternative in the developing nations.

Simultaneous detection of hepatitis C virus antigen and antibodies in dried blood spots.

BACKGROUND: Enzyme immunoassays (EIA) designed to detect hepatitis C virus (HCV) core antigen and anti-HCV antibodies (HCV AgAb) simultaneously can improve the early detection of HCV infection when molecular diagnostic methods are not widely available. OBJECTIVES: To evaluate the suitability of dried blood spot (DBS) samples for detecting HCV AgAb using commercial EIAs. STUDY DESIGN: Paired serum and DBS samples were assayed using two commercial EIAs for HCV AgAb (Monolisa™ HCV AgAb ULTRA and Murex HCV AgAb). Manufacturer's recommendations were followed for sera while sample volume, incubation time and cut-off (CO) determination were evaluated for the DBS samples. The values of sensitivity, specificity, inter-rater agreement, detection limit, assay precision and stability of DBS samples at different conditions (22-26°C, 2-8°C and -20°C) were determined. RESULTS: It was necessary to increase the DBS sample volume fourfold compared to the sera samples to approximate the DBS Optical Density (OD) values to the sera OD values. Using ROC curve to recalculate CO values for the DBS samples, sensitivity was 97.5% for both EIAs, while the specificity was 99.71% for Monolisa™ HCV AgAb ULTRA and 95.95% for Murex HCV AgAb. Accurate testing results were obtained with DBS samples for 60 days at all conditions evaluated; storage at -20°C resulted in low OD variation. Both EIAs demonstrated the same limit of detection among DBS samples [estimated viral load of 3.1 International Units per millilitre (IU/mL)] and low OD value variability in repetitivity and reproducibility studies. CONCLUSION: DBS samples can be used for the detection of HCV AgAb by EIA as they present comparable performance characteristics and excellent stability among various storage conditions.

Diagnosis of patients with suspected chronic hepatitis C infection.

The current optimal approach to detecting hepatitis C virus (HCV) infection involves screening people for risk factors and only testing selected individuals at risk. Blood transfusion from infectious donors, unsafe therapeutic injection practices, and illegal intravenous drug use have been the predominant modes of transmission of HCV infection. Virological markers that are currently used for the clinical management of patients with hepatitis C include serologic assays (ELISA or immunoblot assays), which detect specific antibodies (IgG) to HCV, and virological assays, which detect serum HCV RNA, by highly sensitive qualitative and quantitative techniques. The applicability of these tests is for the diagnoses and monitoring of the treatment but they have no role in the assessment of disease severity or prognosis. Patients diagnosed with HCV infection must be educated in order to avoid the spread of the disease to other people.

Hepatitis C: datos epidemiológicos de Tucumán y Argentina / Hepatitis C: epidemiological data from Tucumán and Argentina

Hemos entrado en un nuevo siglo, un nuevo milenio y al mismo tiempo en la 2a. década de la hepatitis C. En la actualidad existen en Tucumán y Argentina algunos estudios retrospectivos y otros probables a corto plazo, pero todavía son insuficientes para predecir estadísticamente cuál será la progresión de la enfermedad. Se encontró que en Tucumán y ciertas regiones de Argentina la prevalencia de hepatitis C es menor del 1 por ciento. Los factores de riesgo asociados a la misma en Tucumán son en su mayoría debido a transfusiones y la relevancia de la patología alcohólica en su progreso a la cronicidad. Los resultados obtenidos avalan la necesidad de que los gobiernos se interesen en el problema que la hepatitis C representa para la salud pública, destinando medios y recursos para el tratamiento gratuito en los sistemas sociales y también para investigación. Los datos epidemiológicos son cruciales en la prevención de la hepatitis C. Para contener la expansión de VHC primero debemos reconocer que la enfermedad existe, conocer su epidemiología, su cuadro clínico y los factores de riesgo para así evitar su contagio. La primera defensa contra cualquier enfermedad es el conocimiento. (AU)

Hepatitis C: datos epidemiológicos de Tucumán y Argentina / Hepatitis C: epidemiological data from Tucumán and Argentina

Hemos entrado en un nuevo siglo, un nuevo milenio y al mismo tiempo en la 2a. década de la hepatitis C. En la actualidad existen en Tucumán y Argentina algunos estudios retrospectivos y otros probables a corto plazo, pero todavía son insuficientes para predecir estadísticamente cuál será la progresión de la enfermedad. Se encontró que en Tucumán y ciertas regiones de Argentina la prevalencia de hepatitis C es menor del 1 por ciento. Los factores de riesgo asociados a la misma en Tucumán son en su mayoría debido a transfusiones y la relevancia de la patología alcohólica en su progreso a la cronicidad. Los resultados obtenidos avalan la necesidad de que los gobiernos se interesen en el problema que la hepatitis C representa para la salud pública, destinando medios y recursos para el tratamiento gratuito en los sistemas sociales y también para investigación. Los datos epidemiológicos son cruciales en la prevención de la hepatitis C. Para contener la expansión de VHC primero debemos reconocer que la enfermedad existe, conocer su epidemiología, su cuadro clínico y los factores de riesgo para así evitar su contagio. La primera defensa contra cualquier enfermedad es el conocimiento.

Seroprevalencia de anti-VHC, coexistencia de AG-HBS, anti HBC y HIV, and algunos factores de riesgo en donantes anti VHC / The anti-HCV seroprevalence, the coexistence of AG-HBS, anti-HBC and VIH, and some risk factors in positive anti-HCV donors

La seroprevalencia de Anti-VHC, la coexistencia de Ag-HBs, Anti-HBc, HIV y algunos factores de riesgo en donantes Anti-VHC positivo del Banco de Sangre "Jesús Boada Boada" de Barquisimeto durante enero-junio de 1999, se determinó a través de un estudio descriptivo transversal,donde la población y muestra estuvo conformada por el total de donantes voluntarios de sangre (3381), de los cuales 47 resultaron Anti-VHC positivo según la prueba ABBOTT HCV EIA 3.0. Se encontró una seroprevalencia de 1,21 por ciento; el 17.02 por ciento resultaron positivos también para Anti-HBc y 4.26 por ciento tienen positividad simultanea Ag-Hbs y Anti-HBc. Se realizó a 27 donantes voluntarios seropositivos visitas domiciliarias para citarlos al Ambulatorio Urbano tipo II "Pueblo Nuevo" donde se aplicó una encuesta estructural mediante la entrevista. el 88,89 por ciento pertenecen al sexo masculino, el 77,78 por ciento se ubica entre los 15 y 35 años; entre los principales factores de riesgo se encontró que el 81,48 por ciento estuvo en contacto con agujas e instrumental no estéril ó de esterilidad dudosa, 59.09 por ciento tuvo heridas accidentales en barberías, el 76 por ciento con vida sexual activa 3 ó más parejas sexuales y el 100 por ciento son heterosexuales, con ocupación de bajo riesgo para adquirir la infección, desconocen la seropositividad de sus parejas sexuales y del grupo familiar con el cual conviven