Hepatitis C Virus Core Antigen Research Articles

A novel test and treat program for hepatitis C virus infection utilizing HCV core antigen testing, among police and general population, Islamabad, Pakistan, 2022.

Hepatitis C virus core antigen (HCVcAg) testing can simplify and decrease costs of HCV infection confirmation compared to molecular testing (nucleic acid testing). We piloted HCVcAg testing for the confirmation of active infection. The study was conducted during June through December 2022 among the police and the general population of Islamabad, Pakistan age 18 years and older. Initial screening for HCV antibody was conducted using a rapid diagnostic test (RDT) for all consenting participants. Those who tested positive had venous blood samples tested for HCVcAg, platelets and aspartate aminotransferase (AST). Persons with HCVcAg values ≥3 fmol/L were defined as viremic, and they were offered treatment with direct acting antiviral (DAA) medications, sofosbuvir and daclatasvir. Aspartate aminotransferase to platelet ratio index (APRI) was calculated for each HCV infected person, and those with an APRI score <1.5 received treatment for 12 weeks, while those with APRI ≥ to 1.5 received 24 weeks of treatment. A total of 15,628 persons were screened for anti-HCV using RDT and 643 (4.1%) tested positive. HCVcAg values of ≥3 fmol/L was found in 399/643 (62.1%), and all were offered and accepted treatment. Of those treated, 273/399 (68.4%) returned for a follow-up SVR and HCVcAg was not detected in 261/273, a 95.6% cure rate. The pilot study demonstrated the effectiveness of reaching and treating an urban population using RDT for screening and HCVcAg for confirmation of infection and test of cure.

Hepatitis C virus core antigen: A diagnostic and treatmentmonitoring marker of hepatitis C virus in Indian population.

The diagnosis and treatment monitoring of hepatitis C is quite challenging. The screening test, i.e. antibody assay, is unable to detect acute cases, while the gold standard hepatitis C virus (HCV) reverse transcriptase polymerase chain reaction (RTPCR) assay is not feasible in resource-limited countries such as India due to high cost and infrastructure requirement. European Association for the Study of the Liver and World Health Organization have approved a new marker, i.e. HCV core antigen (HCVcAg) assay, as an alternative to molecular assay. In this study, we have evaluated HCVcAg assay for diagnosis and treatment monitoring follow-up in Indian population infected with hepatitis C. Blood specimen of 90 clinically suspected cases of acute hepatitis C were tested simultaneously for anti-HCV antibody assay via ELISA (enzyme-linked immunoassay), HCVcAg assay by chemiluminescence immune assay (CLIA) and HCV RTPCR VL (viral load) assay. Thirty-four HCV RTPCR positive patients were further enrolled in treatment monitoring group whose blood samples were tested at thebeginning of treatment, twoweeks, fourweeks and 12weeks via HCV core Ag assay and HCV RTPCR Viral Load assay. Considering HCV RTPCR as gold standard, diagnostic performance of HCV core Ag assay and anti-HCV antibody assay was evaluated. The sensitivity and specificity of HCV core Ag assay were higher than that of anti-HCV Antibody assay, i.e. 88.3% and 100% vs. 23.3% and 83.3%, respectively. The overall diagnostic accuracy of HCV core Ag assay was 92.20%. Among treatment follow-up group, HCV core Ag levels correlated well with HCV viral load levels, at the beginning of treatment (baseline) till 12weeks showing highly significant Spearman rank correlation coefficient of > 0.9 with HCV viral load levels. HCV core Ag assay is a cost-effective, practically feasible substitute of HCV RTPCR viral load assay for diagnosis as well as long duration treatment monitoring of hepatitis C infection in resource-limited settings.

Performance of HCV core antigen and PCR testing in a predominantly genotype 3 population.

Hepatitis C core antigen (HCVcAg) is becoming increasingly recognized as an alternative to molecular testing for the confirmation of chronic hepatitis C. However, there are limited data on the performance of this assay in a genotype 3 (GT3) predominant country like Pakistan. We conducted a study to evaluate the diagnostic performance of HCVcAg against the HCV polymerase chain reaction (PCR) molecular test. HCV antibody-positive patients requiring confirmatory testing were recruited from August to October 2018 at the Pakistan Kidney and Liver Institute and Research Center (PKLI&RC), Lahore, Pakistan. Patients with previously known diagnoses or treatment histories were excluded. The Abbott HCV Ag assay was used for HCVcAg testing. Results ≥3.00 fmol/L were considered positive for HCVcAg. The Abbott RealTime HCV assay was used for PCR testing with a lower detection limit of ≥12 IU/mL. We computed the sensitivity, specificity and correlation of HCVcAg against HCV PCR. A total of 394 patients were recruited. The median age of the patients was 42 years. Most participants were females (51.5%, n = 203), 30.7% (n = 121) had HTN, 10.4% DM (n = 41) and 5% had APRI ≥2. The overall sensitivity was 98.0% and the specificity was 98.6%. The lowest detection limit of cAg was an HCV RNA value of 4657 IU/mL. The levels of cAg were highly correlated with those of HCV RNA by Spearman's rank correlation test (r = 0.935, p < .001). HCVcAg represents a suitable alternative with high sensitivity and specificity compared with HCV PCR in the GT3-predominant population and can be incorporated into algorithms to improve linkage to care.

Evaluation of the accuracy of a multi-infection screening test based on a multiplex immunoassay targeting imported diseases common in migrant populations

BackgroundWe aimed to evaluate the performance of a novel multiplex serological assay, able to simultaneously detect IgG of six infections, as a screening tool for imported diseases in migrants. MethodsSix panels of 40 (n = 240) anonymized serum samples with confirmed infections were used as positive controls to assess the multiplex assay's sensitivity. One panel of 40 sera from non-infected subjects was used to estimate the seropositivity cutoffs, and 32 non-infected sera were used as negative controls to estimate each serology's sensitivity and specificity. The multi-infection screening test was validated in a prospective cohort of 48 migrants from endemic areas.The sensitivity of the Luminex assay was calculated as the proportion of positive results over all positive samples identified by reference tests. The specificity was calculated using 32 negative samples. Uncertainty was quantified with 95 % confidence intervals using receiver operating characteristic analyses. ResultsThe sensitivity/specificity were 100 %/100 % for HIV (gp41 antigen), 97.5 %/100 % for Hepatitis B virus (HBV-core antigen), 100 %/100 % for Hepatitis C virus (HCV-core antigen), 92.5 %/90.6 % for strongyloidiasis [31-kDa recombinant antigen (NIE)], 97.5 %/100 % for schistosomiasis (combined serpin Schistosoma mansoni and S.haematobium antigens) and 95 %/90.6 % for Chagas disease [combined Trypanosoma cruzi kinetoplastid membrane protein-11 (KMP11) and paraflagellar rod proteins 2 (PFR2) antigens].In the migrant cohort, antibody response to the combination of the T.cruzi antigens correctly identified 100 % individuals, whereas HBV-core antigen correctly identified 91.7 % and Strongyloides-NIE antigen 86.4 %. ConclusionsWe developed a new, robust and accurate 8-plex Luminex assay that could facilitate the implementation of screening programmes targeting migrant populations.

A-244 Performance Comparison of the Alinity i Hepatitis C Core Antigen Assay in Routine Laboratory Testing vs HCV RNA Testing

Abstract Background The elimination of Hepatitis C by 2030 is a goal established by the WHO and other country specific health organizations worldwide. This goal is enabled by the availability of effective treatment regimens. A recent surprise in the US has been the increase in HCV infections during the COVID 19 pandemic, which may be caused by increased needle sharing. HCV Antibody assays have been used to screen for HCV, but confirmation of acute infection is relegated in the current US guidelines to PCR which often takes multiple days and may result in a loss to follow up and treatment, especially in high prevalence populations. HCV Core Antigen is a new immunoassay on the Alinity i system. The aim of the study was to evaluate the precision, linearity, and sensitivity of this research use assay in a US-based population. Methods Alinity i assay HCV Ab is an automated chemiluminescent immunoassay built to measure total antibody to the virus. Similarly, the Alinity i HCV Core Ag is a research use only automated chemiluminescent immunoassay for detection of HCV Core antigen in human plasma and serum. Precision (repeatability, and reproducibility) was determined over 3 days (4–10 replicates/day) using control material consisting of a negative human plasma control, and positive controls made with recombinant core Ag in buffer. Linearity was evaluated by preparing 4 dilutions of a remnant specimen with detectable HCV RNA viral load. Clinical sensitivity was determined using 90 remnant specimens with positive HCV Ab results. Specimens were confirmed positive for Hepatitis C via HCV RNA quantitation using the Aptima HCV Quant Dx transcription-mediated amplification (TMA) assay on the Panther System. Correlation between the HCV Ag assay and TMA was evaluated using specimens submitted for either Hepatitis C infection screening and monitoring of known infection. Results The repeatability of the HCV Ag assay ranged between 3.7% and 11.1% CV depending on the sample S/CO level tested. Dilution recovery averaged 98.2% (range 90.2%–107.3%) and a plot of HCV Ag concentration vs dilution factor showed a correlation coefficient R = 0.998 The Hepatitis C core antigen assay had a correlation coefficient R = 0.92 with the TMA. The HCV assay demonstrated a clinical sensitivity of 96.7% vs TMA. Conclusion The performance characteristics of the Alinity i HCV Core Ag assay highlight an opportunity to speed time to treatment by reflexing on the same instrument from HCV Ab to Ag and confirming effectiveness of treatment.

Lessons Learned From Global Hepatitis C Elimination Programs.

In 2016, the World Health Organization introduced global targets for the care and management of hepatitis C virus (HCV) infection to eliminate hepatitis C as a public health threat by 2030. Despite significant improvements in testing and treatment, in 2020 only 23% of all persons infected with HCV globally were diagnosed. We explore examples from global hepatitis C programs in Georgia, Rwanda, and Nigeria that have used decentralized and integrated models to increase access to HCV testing. Georgia established the world's first national hepatitis C elimination program in 2015. In 2022, 2.6 million people (80% of the adults) have been screened for antibodies for HCV infection, and 80 000 persons with HCV RNA detected were treated. To achieve these results, Georgia implemented HCV core antigen testing, utilization of point-of-care (POC) HCV RNA testing, and simplification of HCV viremia detection by qualitative HCV RNA testing. Rwanda was the first country in sub-Saharan Africa to commit to HCV elimination in 2018, and as of 2022 it has achieved its screening target of 7 million people and initiated approximately 60 000 patients on hepatitis C treatment by rapid decentralization and integration of HCV services. In Nigeria, the integrated near-POC testing approach in Nasarawa State has been effective in expanding access to HCV viremia testing and enabling the possibility of same-day testing and treatment initiation. Examples of decentralization and integration of HCV testing and linkage to care in Georgia, Rwanda, and Nigeria could help inform effective strategies to reach 2030 hepatitis C elimination goals in other countries.

Impact of storage time in dried blood samples (DBS) and dried plasma samples (DPS) for point-of-care hepatitis C virus (HCV) RNA quantification and HCV core antigen detection.

The scale-up of hepatitis C virus (HCV) diagnosis and treatment requires affordable and simple tools to improve access to care, especially in low- and middle-income settings with limited infrastructure or high-risk populations. Dried blood and plasma samples (DBS and DPS) are useful alternative for hepatitis C detection in settings lacking adequate infrastructure. We evaluated the performance of DBS and DPS vs plasma in a point-of-care HCV RNA quantitative assay (Xpert HCV Viral Load-Cepheid), and compared HCV core antigen (HCVcAg) detection by the Architect HCV core antigen assay (Abbott) in DBS vs serum. The dried samples were stored at room temperature for different storage times to reproduce the time from sampling to testing in settings with centralized diagnosis or when testing mobile populations. HCV RNA quantification in DBS and DPS presented 100% sensitivity and specificity and a high correlation for up to 3 months of storage. HCV viremia showed a mean decrease of 0.5 log10 IU/mL (DBS) and 0.3 log10 IU/mL (DPS) for storage times up to 1 month. Architect HCVcAg detection presented high sensitivity/specificity (96%/100%) in DBS tested immediately after sampling, decreasing to 86% sensitivity after 7 days of storage. However, sensitivity increased when an optimized cut-off was applied for each storage time. We conclude that DBS and DPS are suitable samples for HCV RNA detection and quantification, being DPS more reliable for shorter storage times. DBS can be also used for HCVcAg qualitative detection and the sensitivity can be increased when adjusting the cut-off values. IMPORTANCE Hepatitis C infection remains a global burden despite the effectiveness of antivirals. In the WHO roadmap to accomplish HCV elimination by 2030, HCV diagnosis is one of the main targets. However, identifying patients in resource-limited settings and high-risk populations with limited access to healthcare remains a challenge and requires innovative approaches that allow decentralized testing. The significance of our research is in verifying the good performance of dried samples for HCV diagnosis using two different diagnostics assays and considering the effect of room temperature storage in this sample format. We confirmed dried samples are an interesting alternative for HCV screening and reflex testing in resource-limited settings or high-risk populations.

Validation and Sensitivity of HCV Core Antigen in Patient with HCV Infection in Diagnosis and Monitoring Post DAA Therapy

Abstract Background Successful eradication of hepatitis C virus (HCV) has great impact on the prognosis of HCV-related complications and the associated mortality. The development of the new directacting antiviral drugs (DAAs) has revolutionized the treatment of HCV infection. HCV core antigen (HCVcAg) is a recently developed marker that displayed a good correlation with HCV RNA assays, Aim of the Work to evaluate the clinical utility of hepatitis C virus core antigen in detection of chronic hepatitis C virus at pre-treatment and eradication of HCV post DAAs treatment using core antigen ELISA and detection of its sensitivity and specificity in comparison to HCV RNA, Subjects and Methods This was Cross sectional study, carried out at El Galaa and Kobri Al koba military hospitals on 90 Egyptian individuals, divided into 3 groups: (Group A); included 30 healthy individual with HCV Ab and HCV RNA negative as a control, (Group B); included 30 patients with chronic HCV infection in pre-treatment, (Group C): included 30 patients who have received anti HCV treatment (DAAs) 12 weeks post treatment, Result There were insignificant correlation between laboratory parameters of the patient group with HCV-cAg before treatment, Conclusion Fast and immediate results, lower costs of the technique are some of the main advantages of HCVcAg. Therefore, ELISA for HCV-cAg can replace the high sensitivity HCV RNA molecular assay to confirm the presence of HCV infection and to monitor treatment outcome especially in low-income countries with limited resources,

Production and characterization of monoclonal antibodies for the detection of the hepatitis C core antigen.

Background: Despite highly effective treatments to cure hepatitis C, almost 80% of chronically HCV-infected people are not treated, as they are unaware of their infection. Diagnostic rates and linkage to care must be substantially improved to reverse this situation. The HCV core antigen (HCVcAg) is a highly conserved protein that can be detected in the blood of HCV-infected patients and indicates active infection. Aim: To produce murine monoclonal antibodies against HCVcAg suitable for rapid and inexpensive tests to detect HCV infection. Methods: BALB/c mice were sequentially inoculated with purified recombinant HCVcAg from Gt1a, Gt3a, Gt4a, and Gt1b genotypes. Hybridomas producing the desired monoclonal antibodies were selected, and the reactivity of antibodies against HCVcAg from various genotypes was tested by Western blotting and dot blotting. The binding kinetics of the antibodies to purified HCVcAg was analyzed by surface plasmon resonance (SPR), and their ability to detect HCVcAg was tested by double antibody sandwich ELISA (DAS-ELISA). Results: Four specific monoclonal antibodies (1C, 2C, 4C, and 8C) were obtained. 1C, 2C, and 4C recognized HCVcAg of all genotypes tested (Gt1a, Gt1b, Gt2a, Gt3a, and Gt4a), while 8C did not recognize the Gt2a and Gt3a genotypes. Based on SPR data, the antibody-HCVcAg complexes formed are stable, with 2C having the strongest binding properties. DAS-ELISA with different antibody combinations easily detected HCVcAg in culture supernatants from HCV-infected cells. Conclusion: Specific and cross-reactive anti-HCVcAg monoclonal antibodies with strong binding properties were obtained that may be useful for detecting HCVcAg in HCV-infected samples.

An amino acid substitution in HCV core antigen limits its use as a reliable measure of HCV infection compared with HCV RNA.

Hepatitis C virus (HCV) is a viral pathogen that causes chronic hepatitis, which can lead to cirrhosis and hepatocellular carcinoma. Detection of HCV RNA is the standard method used to diagnose the disease and monitor antiviral treatment. A quantification assay for the HCV core antigen (HCVcAg) has been proposed as a simplified alternative to the HCV RNA test for predicting active HCV infection, with the aim of achieving the global goal of eliminating hepatitis. The objective of this study was to determine the correlation between HCV RNA and HCVcAg, as well as the impact of amino acid sequence heterogeneity on HCVcAg quantification. Our findings demonstrated a strong positive correlation between HCV RNA and HCVcAg across all HCV genotypes (1a, 1b, 3a, and 6), with correlation coefficients ranging from 0.88 to 0.96 (p < 0.001). However, in some cases, samples with genotypes 3a and 6 exhibited lower HCVcAg levels than expected based on the corresponding HCV RNA values. Upon the core amino acid sequence alignment, it was observed that samples exhibiting low core antigen levels had an amino acid substitution at position 49, where threonine was replaced by either alanine or valine. Core mutation at this position may correlate with one of the epitope regions recognized by anti-HCV monoclonal antibodies. The present findings suggest that the utilization of HCVcAg as a standalone marker for HCV RNA might not provide adequate sensitivity for the detection of HCV infection, especially in cases where there are variations in the amino acid sequence of the core region and a low viral load of HCV RNA.

Trends in hepatitis C virus coinfection and its cascade of care among adults living with HIV in Asia between 2010 and 2020.

Chronic hepatitis C virus (HCV) infection contributes to substantial morbidity and mortality among adults living with HIV. Cascades of HCV care support monitoring of program performance, but data from Asia are limited. We assessed regional HCV coinfection and cascade outcomes among adults living with HIV in care from 2010-2020. Patients ≥18 years old with confirmed HIV infection on antiretroviral therapy (ART) at 11 clinical sites in Cambodia, China, India, Indonesia, South Korea, Thailand and Vietnam were included. HCV- and HIV-related treatment and laboratory data were collected from those with a positive HCV antibody (anti-HCV) test after January 2010. An HCV cascade was evaluated, including proportions positive for anti-HCV, tested for HCV RNA or HCV core antigen (HCVcAg), initiated on HCV treatment, and achieved sustained virologic response (SVR). Factors associated with screening uptake, treatment initiation, and treatment response were analyzed using Fine and Gray's competing risk regression model. Of 24,421 patients, 9169 (38%) had an anti-HCV test, and 971 (11%) had a positive result. The proportion with positive anti-HCV was 12.1% in 2010-2014, 3.9% in 2015-2017, and 3.8% in 2018-2020. From 2010 to 2014, 34% with positive anti-HCV had subsequent HCV RNA or HCVcAg testing, 66% initiated HCV treatment, and 83% achieved SVR. From 2015 to 2017, 69% with positive anti-HCV had subsequent HCV RNA or HCVcAg testing, 59% initiated HCV treatment, and 88% achieved SVR. From 2018 to 2020, 80% had subsequent HCV RNA or HCVcAg testing, 61% initiated HCV treatment, and 96% achieved SVR. Having chronic HCV in later calendar years and in high-income countries were associated with increased screening, treatment initiation or achieving SVR. Older age, injecting drug use HIV exposure, lower CD4 and higher HIV RNA were associated with reduced HCV screening or treatment initiation. Our analysis identified persistent gaps in the HCV cascade of care, highlighting the need for focused efforts to strengthen chronic HCV screening, treatment initiation, and monitoring among adult PLHIV in the Asia region.

Telomerase Expression Related with Poor Immune Response to HCV Core Antigen in Egyptian HCV Patients’ PBMCs

IntroductionHepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver.AimThis study aimed to assess serum hTERT level and its relation to the progression of liver disease. Also, it aimed to assess the effect of HCV core protein on memory T-cells in HCV patients with or without HCC, and the correlation between memory cells phenotype and the progression of the disease in the same patients.MethodsHTERT level in serum was assessed through relative quantitative RT-PCR. Flow cytometric analysis was used to assess T-cells responsiveness (as IFN-γ secretion) before and after stimulation with HCV core protein, and memory CD8+ cells phenotype using several differentiation markers.ResultsHTERT was found to be increased in a stepwise manner upon comparing its level in controls, chronic hepatitis patients, cirrhotic patients, and HCC patients. T-cells showed a similar manner of stepwise decrease in response (decreased IFN-γ secretion) in HCC patients compared to HCV patients without HCC and controls. Also, late differentiated memory cells (CD8+ CD27- CD28- CD45RA+CCR7-) were depleted in HCC patients compared to HCV patients without HCC.ConclusionThese results suggest a negative correlation between hTERT and IFN-γ secretion by T- cells in HCV patients and that this relationship along with the depletion of late differentiated memory cells could help the progression of liver disease to HCC.

Quantitative and Qualitative Evaluation of Hepatitis C Virus Core Antigen (HCVcAg) as an Alternative Diagnostic Marker in Chronic HCV Infection

Quantitative and Qualitative Evaluation of Hepatitis C Virus Core Antigen (HCVcAg) as an Alternative Diagnostic Marker in Chronic HCV Infection

Hepatitis C virus (HCV) infection in Malaysia: findings from a nationwide cross-sectional study

Hepatitis C virus (HCV) infection in Malaysia: findings from a nationwide cross-sectional study

Evaluation of the Correlation of HCV Core Antigen Levels with HCV RNA Levels in the Diagnosis and Treatment Follow-up of Hepatitis C Virus Infections

Hepatitis C virus (HCV) infections are an important public health issue across the world because of the high risk of chronicity potential, impossibility of protection by vaccination and serious complications such as hepatocellular carcinoma. The aim of this study was to evaluate the correlation of HCV core antigen test with HCV RNA in the diagnosis and treatment follow-up and to discuss the status of being an alternative test in routine use. In the first step of the study, the compatibility of the methods was investigated by applying the HCV core antigen test to 600 serum samples from patients with pre diagnosis of HCV infection for whom anti-HCV and HCV RNA tests were routinely studied in the molecular microbiology laboratory of medical microbiology department between December 2016 and December 2018. In the second step, in addition to the routine HCV RNA test, HCV core antigen test was studied in serum samples taken before the start of the treatment, at the eighth week of the treatment and at the end of the treatment of 150 patients whose treatment were decided by the gastroenterology department within this period. The correlation between the two tests was evaluated during the treatment follow-up. Forty-nine of 600 patients were diagnosed according to test results. In 28 patients, HCV core antigen was positive in addition to HCV RNA and anti-HCV which were routinely studied. The sensitivity of HCV core antigen test was 91.49%, specificity was 100%, PPD was 100%, NPD was 97.30%, accuracy was 87.76%. There was a high correlation between HCV RNA and HCV core antigen results. In the second step of the study, sensitivity (96.52%), specificity (95.28%), PPD (95.11%), NPD (95.80%) and accuracy (92.58%) of the HCV core antigen test were determined. These results show that there is a high correlation between the two tests and that HCV core antigen test can be used as an alternative test to HCV RNA test as it is an easily applicable and cost effective test during diagnosis and treatment follow-up.

Seroprevalence of hepatitis C virus in Jinan, China, 2008–2020

BackgroundThe updated estimates of hepatitis C virus (HCV) seroprevalence are critical for developing strategies to manage or eliminate HCV infection.MethodsA comprehensive study on HCV seroprevalence was conducted among 365,210 patients at Jinan Central Hospital, China, from 2008 to 2020. The patients were tested for anti-HCV, HCV core antigen, hepatitis B surface antigen, syphilis antibody, human immunodeficiency virus antigen + antibody, antihepatitis A virus IgM, and antihepatitis E virus IgM.ResultsHCV seroprevalence was 0.79% and was related to age. HCV seropositivity was lower in children (aged < 18 years) than in adults (aged ≥ 18 years) (0.15% vs. 0.81%). High HCV prevalence was reported in adults aged ≥ 41 years, and HCV seropositivity in those aged 41–80 years accounted for 74.56% of all seropositive individuals. Notably, the rate of HCV–HIV coinfection was 0. HCV seroprevalence was considerably higher in patients at the Kidney Disease Unit and Dialysis Department than in those at other departments (inpatient or outpatient).ConclusionsHCV seroprevalence was lower in Jinan region but higher in patients at the Kidney Disease Unit and Dialysis Department, especially in those undergoing hemodialysis.

Seroprevalence of Hepatitis C Virus Infection among Hemodialysis Patients in A Tertiary Care Hospital in South India

Hepatitis C virus (HCV) infection in hemodialysis patients is mainly associated with insufficient precautionary measures. Compared with the general population, the prevalence of HCV infection is high among hemodialysis patients. HCV infection in these patients is typically associated with increased morbidity and mortality; however, the early detection of HCV may retard disease progression and reduce morbidity and mortality. In this study, we sought to estimate the seroprevalence of HCV infection among patients undergoing hemodialysis in a tertiary care hospital in Chennai, Tamil Nadu, South India. This was a prospective, observational, cross-sectional study that included 82 hemodialysis patients. Blood samples were collected from each patient, and the serum was separated for detection of the presence of HCV antibodies, HCV core antigen, and HCV RNA using an enzyme-linked immunosorbent assay, enzyme immunoassay, and polymerase chain reaction, respectively. Relevant socio-demographic, clinical, and laboratory information was also obtained. Among samples collected from the 82 patients, seven were found to be positive for HCV antibodies, whereas nine and eleven samples were found to be positive for HCV core antigen and HCV RNA, respectively. Long durations of renal failure and hemodialysis were identified as being positively associated with HCV infection in these hemodialysis patients, and a statistically significant reduction in hemoglobin levels and an increase in creatinine levels were detected among the HCV-positive patients. The overall seroprevalence of HCV infection in hemodialysis patients was found to be 13.4%. Given that high rate false-negative reactions were detected using ELISA and EIA, screening of HCV RNA during the early stages of HCV infection can contribute to preventing its nosocomial spread in these patients. Moreover, it is imperative that stringent universal precautionary measures are implemented in all health care settings and hemodialysis units to minimize the risk of HCV transmission.

Diagnostic performance of hepatitis C core antigen assay to identify active infections: A systematic review and meta-analysis.

Hepatitis C virus (HCV) core antigen (HCVcAg) assay is an alternative for diagnosing HCV infection in a single step. This meta-analysis aimed to evaluate the Abbott ARCHITECT HCV Ag assay's diagnostic performance (validity and utility) for diagnosing active hepatitis C. PubMed, EMBASE, Scopus, Web of Science, and Cochrane Library were searched until 10 January 2023. The protocol was registered at the prospective international register of systematic reviews (PROSPERO: CRD42022337191). Abbott ARCHITECT HCV Ag assay was the test for evaluation, and nucleic acid amplification tests with a cut-off ≤50IU/mL were the gold standard. Statistical analysis was performed using STATA with the MIDAS module and random-effects models. The bivariate analysis was conducted on 46 studies (18,116 samples). The pooled sensitivity was 0.96 (95% CI=0.94-0.97), specificity 0.99 (95% CI=0.99-1.00), positive likelihood ratio 141.81 (95% CI=72.39-277.79), and negative likelihood ratio 0.04 (95% CI=0.03-0.06). The area under the summary receiver operating characteristic curve was 1.00 (95% CI=0.34-1.00). For active hepatitis C prevalence values of 0.1%-15%, the probability that a positive test was a true positive was 12%-96%, respectively, indicating that a confirmatory test should be necessary, particularly with a prevalence ≤5%. However, the probability that a negative test was a false negative was close to zero, indicating the absence of HCV infection. The validity (accuracy) of the Abbott ARCHITECT HCV Ag assay for screening active HCV infection in serum/plasma samples was excellent. Although the HCVcAg assay showed limited diagnostic utility in low prevalence settings (≤1%), it might help diagnose hepatitis C in high prevalence scenarios (≥5%).

Longitudinal assessment of HCV core antigen kinetics to monitor therapeutic response in the age of DAAs.

In the economy of therapeutic monitoring, an affordable viral marker is essential in the era of direct-acting antivirals (DAAs). We elucidated the kinetics of HCVcAg to delineate its precise role in monitoring therapeutic response. In this longitudinal study, 3208 patients were tested for HCV RNA. A total of 423 patients were started on DAAs. Treatment response and kinetics of HCVcAg/RNA were assessed in treatment-naïve (n = 383) and previously treated (n = 40) patients with follow-up for 2 years. After the initiation of DAAs, the rate of relapse was significantly higher in the previously treated group than naive group [12.5% (5/40) Vs 2% (7/383), p<0.0001]. The response rate at RVR was significantly higher with HCVcAg than RNA in both groups (p<0.02). The kinetics of HCVcAg and RNA were significantly different at ETR and SVR12 in the naïve (p<0.04), but similar at all therapeutic points in the previously treated group. The correlation between HCVcAg and RNA was good at baseline, ETR and SVR, except RVR in both groups (r>0.6; p<0.0001). Furthermore, HCV genotypes, treatment regimen, CTP (<7/≥7) and MELD (<15/≥15) did not influence the therapeutic response and the viral replication kinetics (p>0.05). It is the first longitudinal study from India shows that the response rate and kinetics of HCVcAg are comparable to HCV RNA for an extended duration, except at RVR, irrespective of the HCV genotypes, treatment regimen, and liver disease severity. Hence, HCVcAg can be considered as a pragmatic marker to monitor therapeutic response and predict relapse in the era of DAAs.

HCV Core-antigen Assay as an Effective Alternative to HCV RNA Quantification in Patients With Hepatitis C.

Hepatitis C virus (HCV) core antigen (Ag) test has been increasingly applied as an effective alternative to conventional molecular tests allowing rapid and affordable diagnosis, which is of paramount relevance to achieve global elimination of HCV infection. ARCHITECT® HCV Ag test was evaluated in comparison with HCV RNA quantification test (CAP/CTM) to calculate its sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and to determine their correlation level. Its performance, according to low and high viral load values and in different treatment stages [during treatment (T), at the end of the therapeutic protocol (EOT) and when sustained virological response (SVR) was evaluated]. In total, 145 samples were included. Considering CAP/CTM, the sensitivity, specificity, PPV and NPV of the HCV-Ag test were 88.9%, 99.1%, 97.0% and 96.4%, respectively, and the correlation among tests was high (r=0.890), with only five discordant results. A decrease in sensitivity was found for low viral load values (<1,000 IU/ml), but the opposite was verified for high viral concentrations (≥1,000 IU/ml). A good agreement was verified for the T and EOT groups (k=0.789 and k=0.638) and an excellent agreement in the SVR group (k=1.000). HCV-Ag seems to be an effective alternative that can be routinely combined with other faster and more accessible tests (e.g., HCV antibody tests) for the identification of new HCV infections in suspected patients, eventually reserving the molecular techniques for samples with discordant results.