Clinical usefulness of total hepatitis C virus core antigen quantification to monitor the response to treatment with peginterferon alpha‐2a plus ribavirin*

Abstract

Early virological response may predict outcome following treatment with peginterferon alpha-2a and ribavirin in patients chronically infected with hepatitis C virus (HCV). As total HCV core antigen may constitute an alternative direct marker to HCV RNA for assessing the levels of viraemia in such patients, we evaluated the correlation between HCV core antigen and HCV RNA, and whether HCV core antigen at baseline, 4 and 12 weeks after treatment could predict sustained virological response (SVR) to combined therapy, in comparison with HCV RNA. A total of 290 serum samples from 58 previously treatment naïve chronic HCV patients were examined for HCV core antigen and HCV-RNA by means of quantitative HCV RNA when receiving combination therapy for the first time. SVR was significantly associated with basal HCV core antigen but not with HCV RNA. There was a good correlation between HCV core antigen and HCV RNA (r(2) = 0.781). The negative predictive value of HCV core antigen testing in predicting nonresponse at weeks 4 and 12 were 75 and 100%, and for undetectable or a 2-log drop in HCV RNA were 69.6 and 75% respectively. HCV core antigen detection is quick, and easy to perform alternative to HCV RNA, and could be used as a marker of HCV viraemia for monitoring the progress of therapy.

Analytical Performance Characteristics and Clinical Utility of a Novel Assay for Total Hepatitis C Virus Core Antigen Quantification

“…Notwithstanding our results, the principal possibility of discrepancies by HCV core antigen and HCV RNA quantification in patients under antiviral treatment should always be kept in mind (4). Furthermore, the findings of the HCV core measurements in patients who receive antiviral treatment are currently difficult to interpret since it is entirely unclear whether or not, e.g., "stop rules" similar to those already established in clinical trials for HCV RNA concentration determinations (27) will be also applicable for the quantitative determination of HCV core antigen (4,13,23,34,42,47). Consequently, at present, it remains unlikely that the Architect HCV Ag assay will be able to find its place in monitoring the response to antiviral treatment of patients chronically infected with HCV (41).…”

“…The detection and quantification of HCV core antigen in the serum or plasma of infected patients by using different assay formats were previously shown to narrow the preseroconversion (window) phase of acute HCV infections (26,30) and to be a useful marker of viral replication (4,5,11,13,23,34,42,47).…”

“…The use of these assays in clinical laboratory settings documented that HCV core antigen can be detected in the serum of individuals during the window period of acute infection (26,30,44). Furthermore, it was conclusively shown that core antigen levels correlate well with HCV RNA concentrations and that quantification of the HCV core protein may consequently be a marker of disease progression (10, 15) or could be used to monitor the response to antiviral therapy in chronically infected patients (4,13,23,34,42). Given the generally favorable performance characteristics of HCV core antigen assays, it seemed reasonable to further refine this analytical format.…”

Evaluation of ARCHITECT HCV Core Antigen Assay

“…HCV core 항원은 항체미검출기간에도 검출이 가능하고 [9], 바이러스 혈증이 동반된 HCV 감염환자에서 HCV core 항 원 정량값과 HCV RNA 정량값의 상관성이 좋다고 알려져 있 다 [10]. 그리고 HCV core 항원은 만성 C형 간염의 임상적 경과 나 항바이러스제 치료 후 반응 평가에도 유용하다고 한다 [11,12]. …”

Evaluation of Hepatitis C Virus Core Antigen Assays in Detecting Recombinant Viral Antigens of Various Genotypes

“…Accurate diagnosis of HCV infection is important due to the morbidity associated with the virus, and determining the level of viral replication is important in predicting and monitoring the effect of antiviral treatment. Although quantifying viral RNA represents the standard method for identifying active infection (5,8,13), several sensitive immunoassays that detect the viral core antigen (Ag) have now been developed as an alternative to HCV RNA testing (3,4,6,9,10,12,16). The amino acid sequence of the core Ag is largely conserved among different viral isolates (14); however, genetic variability of the virus constitutes one of the major challenges to using core Ag assays for diagnosis.…”