Hepatitis C Virus Core Antigen as an Alternative to RNA in the Assessment of Response to Treatment with Direct-acting Oral Antivirals

Background: Affordable and effective diagnostic and treatment monitoring algorithms are urgently needed to achieve the global elimination of hepatitis C virus (HCV) infection. Methods: A total of 274 patients were treated with direct-acting antivirals (DAAs) in the Spanish Hospital of Albacete between 2004 and 2020. This study compared the enzyme-immunoassay technique for HCV core antigen (HCVcAg) with the determination of RNA of HCV (HCV RNA) by polymerase chain reaction (PCR) in monitoring treatment with DAA, setting the lower limit of detection of HCVcAg < 3 fmol/L and RNA < 10 IU/mL. In all cases, the P value of differences associated with the contrast test was less than or equal to 0.05. Results: We evaluated the viral loads of our patients before treatment, during their treatment, and after its completion. The HCV RNA quantification at diagnosis was 2309327 IU/mL. The mean HCVcAg load was 5972 fmol/L. There was a strong correlation between HCVcAg levels and RNA levels with a Spearman rho of 0.832 (P < 0.01). The HCVcAg sensitivity at diagnosis was 99%, but the specificity could not be calculated because there were no true negatives or false positives at this point. Twelve weeks after treatment, in patients with treatment failure, we obtained a mean of 19084 IU/mL for RNA, while for HCVcAg, the mean was 103 fmol/L. At this time point, we also found a strong correlation between HCVcAg levels and HCV RNA levels with a Spearman rho of 0.775 (P < 0.01). Finally, the virological cure was achieved in 99% of our patients. The results for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 100%, 99.87%, 86.33%, and 100%, respectively. Conclusions: HCVcAg determination is an excellent alternative to HCV RNA in the assessment of treatment response. This is particularly relevant in lower- and middle-income countries and resource-limited settings where the high cost of labor, equipment, and reagents can prohibit molecular testing.

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Role of hepatitis C virus core antigen assay in hepatitis C care in developing country

Egyptian Liver Journal ◽

10.1186/s43066-021-00146-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ouafa Kallala ◽

Saoussen Kacem ◽

Imene Fodha ◽

Bruno Pozzetto ◽

Trabelsi Abdelhalim

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Developing Country ◽

Predictive Value ◽

Gold Standard ◽

Hcv Infection ◽

Core Antigen ◽

Hcv Rna ◽

Hcv Genotype ◽

Rna Levels

Abstract Background The World Health Organization (WHO) aims to achieve global hepatitis C elimination by 2030, defined as diagnosis of 90% of infected individuals and treating 80% of them. Current guidelines for the screening and diagnosis of hepatitis C infection denote using a relatively cheap screen with anti-hepatitis C virus (HCV) antibody immunoassay, followed by the much costlier molecular test for HCV RNA levels using polymerase chain reaction (PCR) assay to confirm active HCV infection. Simplification of the HCV evaluation algorithm to reduce the number of required tests could considerably expand the provision of HCV treatment especially in a developing country. This study investigates the performance of hepatitis C Core Antigen (HCV Ag) test by comparing HCV Ag results versus the results obtained with HCV ribonucleic acid (RNA) PCR which is considered the gold standard for the diagnosis of HCV infection. Results Among the 109 anti-HCV positive sera, 96 were positive for both HCV Ag (> 3 fmol/L) and HCV RNA (> 15 IU/mL); 8 were negative for both tests, while the remaining 5 were positive for HCV RNA only. Considering the HCV RNA as gold standard; the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of HCV Ag test were found to be 95.05%, 100%, 100%, and 61.54%, respectively. HCV genotype was performed for 59 patients. The most common HCV genotype was genotype 1 (72.9%). Genotype 2 (15.3%) and genotype 3 (11.9%) were detected in the others samples. A high level of correlation was seen between HCV RNA and HCV Ag (r = 0.958, p < 0.001). The correlation for the samples that were genotyped 1 was significant (r = 0.966, p < 0.001). Conclusion In our study, it was found that there was strong correlation between HCV RNA levels and HCV Ag levels. So, it can be used for a one-step HCV antigen test to diagnose active HCV infection.

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Hepatitis C Virus Core Mutations Reduce the Sensitivity of a Fluorescence Enzyme Immunoassay

Journal of Clinical Microbiology ◽

10.1128/jcm.38.9.3450-3452.2000 ◽

2000 ◽

Vol 38 (9) ◽

pp. 3450-3452 ◽

Cited By ~ 12

Author(s):

Hajime Tokita ◽

Gilbert R. Kaufmann ◽

Mamoru Matsubayashi ◽

Isao Okuda ◽

Tsukasa Tanaka ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Enzyme Immunoassay ◽

Core Region ◽

Core Antigen ◽

Nucleotide Sequencing ◽

Hcv Rna ◽

Virus Core ◽

Hcv Core Antigen ◽

Rna Levels

Four of 107 samples obtained from hepatitis C virus (HCV) carriers showed lower HCV core antigen levels in a fluorescence enzyme immunoassay (FEIA) than expected from corresponding HCV RNA levels. Nucleotide sequencing revealed a mutation in the HCV core region (Thr49Pro) that appears to have reduced the FEIA sensitivity.

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Hepatitis C Virus RNA Levels Following Virologic Failure With Direct-acting Antivirals: Implications for Lower Sensitivity Diagnostic Assays

Clinical Infectious Diseases ◽

10.1093/cid/ciz385 ◽

2019 ◽

Vol 70 (2) ◽

pp. 327-330 ◽

Cited By ~ 1

Author(s):

Patrick R Harrington ◽

Takashi E Komatsu ◽

Hengrui Sun ◽

Lisa K Naeger

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Virologic Failure ◽

Post Treatment ◽

Hcv Rna ◽

Lower Sensitivity ◽

Direct Acting Antivirals ◽

Diagnostic Assays ◽

Direct Acting ◽

Rna Levels

Abstract We analyzed post-treatment hepatitis C virus (HCV) RNA levels from 330 subjects who experienced virologic failure in clinical trials of direct-acting antivirals. We demonstrated that 97% had post-treatment Week 12 HCV RNA >10 000 IU/mL, above reported sensitivity limits of novel diagnostic assays being considered for simplified HCV treatment monitoring.

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The Correlation between Hepatitis C Core Antigen and Hepatitis C Virus RNA Levels with Respect to Human Immunodeficiency Virus Status, Hepatitis C Virus Genotype and Interferon-Lambda-4 Polymorphism

Intervirology ◽

10.1159/000370070 ◽

2015 ◽

Vol 58 (2) ◽

pp. 73-79 ◽

Cited By ~ 5

Author(s):

Vo Duy Thong ◽

Srunthron Akkarathamrongsin ◽

Anchalee Avihingsanon ◽

Apiradee Theamboonlers ◽

Yong Poovorawan ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Liver Stiffness ◽

Human Immunodeficiency Virus Status ◽

Core Antigen ◽

Hcv Rna ◽

Virus Genotype ◽

Hcv Genotypes ◽

Interferon Lambda ◽

Rna Levels

Objectives: Serum hepatitis C virus (HCV) core antigen (HCVcAg) concentrations correlate with HCV RNA levels in HCV monoinfected patients. Data in HCV/HIV coinfected patients are still limited. We aim to compare the use of HCVcAg measurement with respect to HIV status, HCV genotypes, interferon-lambda-4 (IFNL4) polymorphism and clinical parameters. Methods: We analyzed an untreated cohort of 104 patients with HCV monoinfection and 85 patients with HCV/HIV coinfection. Serum HCVcAg was measured by a commercial chemiluminescent microparticle immunoassay. The presence of IFNL4 polymorphism ss469415590 was identified by real-time PCR. Results: log10 HCVcAg levels were significantly correlated with corresponding log10 HCV RNA levels (r = 0.889, p < 0.001), but not with ALT levels and liver stiffness. The correlation between HCV RNA and HCVcAg was particularly high in coinfected patients and those with high viremia. Mean log10 HCVcAg concentration was significantly higher in coinfected patients than in monoinfected patients. Patients harboring the TT/TT genotype of ss469415590 had significantly higher levels of log10 HCVcAg than those with the non-TT/TT genotype. HCVcAg levels were similar across HCV genotypes. Conclusions: HCVcAg concentrations had an excellent correlation with HCV RNA levels, particularly in HCV/HIV-coinfected individuals and might be associated with IFNL4 polymorphism. HCVcAg testing could be used as an alternative to HCV RNA assays in resource-limited settings.

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Hepatitis C virus core antigen assay: an alternative method for hepatitis C diagnosis

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/0004563216661218 ◽

2016 ◽

Vol 54 (2) ◽

pp. 279-285 ◽

Cited By ~ 6

Author(s):

Lijuan Wang ◽

Hong Lv ◽

Guojun Zhang

Keyword(s):

Hepatitis C ◽

Positive Predictive Value ◽

Predictive Value ◽

Characteristic Curve ◽

High Specificity ◽

Receiver Operator Characteristic Curve ◽

Core Antigen ◽

Hcv Rna ◽

Serum Samples ◽

Alternative Method

Background The study aimed to evaluate a fully automated chemiluminescent immunoassay and compared it with a quantitative RNA assay and anti-HCV assay to verify the utility of this automated Ag assay as an alternative method for hepatitis C diagnosis. Methods A total of 229 serum samples previously tested for anti-HCV concentrations by the Architect Anti-HCV assay, were selected for HCV RNA testing by real time RT-PCR kit (Shanghai ZJ Bio-Tec Co., Ltd) and 125 specimens were tested for HCV Ag by the Architect HCV core Antigen kit. Results The log10 HCVAg and HCV RNA concentrations were highly correlated [ r = 0.834); with HCV RNA as the comparator test, HCVAg had 100% specificity, 100% positive predictive value (PPV) and 94.8% sensitivity. We found 1 pg/mL of total HCV core Ag is equivalent to approximately 6607HCV RNA international units (IU)/mL. Receiver operator characteristic curve analysis showed that the area under the curve of HCV core Ag (0.989) was greater than HCV Ab (0.871). HCV Ag concentrations and RNA-to-Ag ratio of the groups for HCV RNA concentrations ≤105 and >105 IU/mL were both significantly different from each other ( P < 0.05). Conclusion The Architect HCV core Ag assay may be an alternative method for hepatitis C diagnosis, performed on the same analytical platform and sample as the anti-HCV assay, shortening the diagnostic window period, demonstrating good correlation with HCV RNA assay with high specificity and positive predictive value.

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Serum Hepatitis C Virus RNA Levels and Histologic Findings in Liver Allografts With Early Recurrent Hepatitis C

Archives of Pathology & Laboratory Medicine ◽

10.5858/2000-124-1623-shcvrl ◽

2000 ◽

Vol 124 (11) ◽

pp. 1623-1627 ◽

Cited By ~ 1

Author(s):

Young Nyun Park ◽

Peter Boros ◽

David Y. Zhang ◽

Patricia Sheiner ◽

Leona Kim-Schluger ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Liver Biopsy ◽

Activity Index ◽

Hcv Rna ◽

Recurrent Hepatitis ◽

Biopsy Specimens ◽

Histologic Activity Index ◽

Recurrent Hepatitis C ◽

Rna Levels

Abstract Background.—Histopathologic features of early recurrent hepatitis C after orthotopic liver transplantation (OLTx) may be modified by immunosuppressive therapy or complicated by other conditions. Hepatitis C virus (HCV) RNA level usually increases after OLTx, but its correlation to histologic findings is not clear. Objective.—To evaluate the histologic findings of early recurrent hepatitis C in liver allografts and its correlation to serum HCV RNA level. Methods.—We studied 14 patients who underwent OLTx for chronic HCV infection. Thirty liver biopsy specimens and HCV RNA levels of 22 corresponding plasma samples obtained during the first 6 months following OLTx were analyzed. The control group (9 patients, 25 biopsy specimens) was chosen at random from patients with chronic liver disease other than HCV who were undergoing OLTx, and all tested negative for HCV RNA by polymerase chain reaction after OLTx. Results.—Statistically significant pathological features of early recurrent HCV infection were the number of acidophilic bodies, piecemeal necrosis, lymphocyte predominance in the portal tracts, and fibrous septum. These findings and histologic activity index scores increased with time after OLTx. The HCV RNA levels determined by branched DNA assay showed no significant correlation with histologic features. However, patients with higher histologic activity index scores tended to have higher RNA levels. Conclusions.—Liver biopsy specimens are helpful for the diagnosis or confirmation of early recurrent hepatitis C in liver allografts, but serial biopsy specimens are sometimes required for definite diagnosis. The HCV RNA levels are usually higher in patients who display signs of more severe liver damage.

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Integrated, Co-located, Telemedicine-based Treatment Approaches for Hepatitis C Virus Management in Opioid Use Disorder Patients on Methadone

Clinical Infectious Diseases ◽

10.1093/cid/ciy899 ◽

2018 ◽

Vol 69 (2) ◽

pp. 323-331 ◽

Cited By ~ 15

Author(s):

Andrew H Talal ◽

Phyllis Andrews ◽

Anthony Mcleod ◽

Yang Chen ◽

Clewert Sylvester ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Multiple Correspondence Analysis ◽

Opioid Use Disorder ◽

Hcv Rna ◽

Directly Observed Therapy ◽

Opioid Use ◽

Hcv Treatment ◽

Opioid Substitution Therapy ◽

Direct Acting

Abstract Background Despite high hepatitis C virus (HCV) prevalence, opioid use disorder (OUD) patients on methadone rarely engage in HCV treatment. We investigated the effectiveness of HCV management via telemedicine in an opioid substitution therapy (OST) program. Methods OUD patients on methadone underwent biweekly telemedicine sessions between a hepatologist and physician assistant during the entire HCV treatment course. All pretreatment labs (HCV RNA, genotype, and noninvasive fibrosis assessments) were obtained onsite and direct-acting antivirals were coadministered with methadone using modified directly observed therapy. We used multiple correspondence analysis, least absolute shrinkage and selection operator, and logistic regression to identify variables associated with pursuit of HCV care. Results Sixty-two HCV RNA–positive patients (24% human immunodeficiency virus [HIV] infected, 61% male, 61% African American, 25.8% Hispanic) were evaluated. All patients were stabilized on methadone and all except 4 were HCV genotype 1 infected. Advanced fibrosis/cirrhosis was present in 34.5% of patients. Of the 45 treated patients, 42 (93.3%) achieved viral eradication. Of 17 evaluated patients who were not treated, 5 were discontinued from the drug treatment program or did not follow up after the evaluation, 2 had HIV adherence issues, and 10 had insurance authorization issues. Marriage and a mental health diagnosis other than depression were the strongest positive predictors of treatment pursuit, whereas being divorced, separated, or widowed was the strongest negative predictor. Conclusions HCV management via telemedicine integrated into an OST program is a feasible model with excellent virologic effectiveness. Psychosocial and demographic variables can assist in identification of subgroups with a propensity or aversion to pursue HCV treatment.

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