Quantitative Determination of Hepatitis C Core Antigen in Therapy Monitoring for Chronic Hepatitis C

Abstract

The correlation and kinetics of hepatitis C virus (HCV) RNA and HCV core antigen levels in chronic hepatitis C patients treated with pegylated interferon + ribavirin were evaluated in order to envision a combined use of the two assays in therapy monitoring. HCV core antigen levels by a chemiluminescent immunoassay (Abbott ARCHITECT) and HCV-RNA levels by branched DNA (bDNA) or real-time PCR have been evaluated on plasma specimens from 32 patients treated for chronic hepatitis C. An early virological response (undetectable levels of HCV-RNA 4 weeks after start of treatment) was found in 10/23 subjects (43.5%) followed up for 5 months or more. The response was linked to the HCV genotype (20% in genotype 1B vs. 61.5% in other genotypes; p < 0.05). HCV RNA and HCV antigen showed a good correlation (r = 0.814); HCV antigen was still detectable in 3 samples with undetectable (<615 IU/ml) RNA by bDNA, while no differences in clinical sensitivity were recorded in comparison with real-time PCR. These findings suggest that HCV-RNA and HCV antigen may be used at different time points in order to tailor therapy monitoring to individual needs.

Hepatitis C virus core antigen: Analytical performances, correlation with viremia and potential applications of a quantitative, automated immunoassay

“…10,11,30,34 In our experience only 21 specimens, or 1.4% of all samples assayed, were truly discordant between HCV Ag and HCV-RNA, and thus the consistency of serological and virological results was very good.…”

Who to test and how to test for chronic hepatitis C infection – 2016 WHO testing guidance for low- and middle-income countries

“…As DAA treatment regimens have become available in LMICs, but NAT testing for HCV RNA remains at high cost and relatively unavailable, the need for access to an affordable and simple diagnostic marker as a test of cure has become even more important. HCVcAg testing has been proposed as an alternative to HCV RNA for the diagnosis of viraemic HCV infection [165,166]. However, there remains debate about whether HCVcAg can also be used as a tool for assessing response to HCV antiviral treatment and to test for cure.…”

“…These assays have a broad dynamic range from 12 to 7,700,000 IU/ml, and a systematic review showed analytical sensitivity as low as 5 IU/ml for qualitative HCV RNA by NAT. Although either assay was recommended, the sensitivity and lower cost of qualitative assays for HCV RNA makes them preferable as a test of cure at 12 weeks or, conversely, presence of virus as an indication of ongoing HCV infection [163][164][165][166][167].…”

Strong Correlation between Liver and Serum Levels of Hepatitis C Virus Core Antigen and RNA in Chronically Infected Patients

“…It has a cutoff of 3 fmol/liter (0.06 pg/ml). Previous studies using this assay have indicated that (i) the time course of HCV Ag levels is similar to those of HCV RNA for all phases of infection (11,17) and (ii) the serum concentrations of HCV Ag and RNA are closely correlated (8-10, 12, 17).…”

“…It has a cutoff of 3 fmol/liter (0.06 pg/ml). Previous studies using this assay have indicated that (i) the time course of HCV Ag levels is similar to those of HCV RNA for all phases of infection (11,17) and (ii) the serum concentrations of HCV Ag and RNA are closely correlated (8-10, 12, 17).However, the HCV Ag assay has not previously been applied to the measurement of intrahepatic HCV Ag levels. The liver is the primary site of HCV replication, and previous work revealed a direct correlation between liver and serum HCV RNA levels (16,(20)(21)(22).…”