The Role of Hepatitis C Virus Core Antigen Testing in the Era of Direct Acting Antiviral Therapies: What We Can Learn from the Protease Inhibitors

Abstract

Direct-acting antiviral (DAA) therapies have revolutionised the treatment of hepatitis C virus (HCV). The financial cost of DAAs however is significant, and first generation protease inhibitors (PIs) also require frequent monitoring of viral RNA levels to guide treatment. In this context, we examined the relevance of HCV antigen testing to evaluate the potential role in monitoring virological response to HCV antiviral treatment with the PI-based triple therapies, telaprevir (TVR) and boceprevir (BOC). Chronic HCV-infected individuals (n = 152) enrolled in the Irish Hepatitis C Outcomes Research Network (ICORN) study were prospectively analysed for baseline markers and the early viral kinetics associated with SVR. The sustained virological response (SVR) rates in the cohort receiving TVR and BOC were 87.3% and 73.8%, respectively. Baseline factors associated with successful outcome in TVR therapy were age (P = 0.0098), IFNL3 genotype (P = 0.0330) and viral load (P = 0.0456). RNA level at week 4 (P = 0.0068) and viral antigen negativity at week 2 (P = 0.0359) were predictive of SVR for TVR-based therapy. In BOC therapy, prior interferon treatment (P = 0.0209) and IFNL3 genotype (P = 0.0410) were baseline predictors of SVR. Evidence of viraemia based either on viral RNA or antigen at week 4 predicted SVR in these patients. Our data showed that rapid decline of HCV antigen to negative level at week 2 in TVR treatment and <0.96 log fmol/l in BOC treatment after commencement of PI triple therapy were associated with SVR. HCV antigen measurement should be considered as a potential alternative for monitoring treatment response during DAA-based regimens.

Clinical utility of hepatitis C virus core antigen assay in the monitoring of direct-acting antivirals for chronic hepatitis C

“…In our study, HCV Ag levels declined more rapidly when compared to HCV RNA in the early stages (undetectability of 63.6% vs. 32.4% at week 2 and 75.3% vs. 64.2% at week 4, respectively). These data were comparable with those reported in earlier studies [18,19]. However, of note, the concordance of HCV Ag and HCV RNA undetectability was significantly different when comparing the ART assay and CTM test.…”

Hepatitis C Virus Core Antigen: A Simplified Treatment Monitoring Tool, including for Post-Treatment Relapse

“…Cost-effective, single-step diagnostic tools for active HCV infection are required to streamline diagnoses and facilitate linkage to care [2,6]. Nucleid-Acid-Tests (NAT) are used currently in clinical practise due to their high specificity, sensitivity and reproducibility, although costs can constrain their utility in resource-limited settings [7]. Likewise, simple tools to confirm cure and detect viral recurrence are critical to facilitate DAA scale-up and HCV elimination, particularly in low and middle income countries.…”

Clinical Evaluation of a Newly Developed Chemiluminescent Enzyme Immunoassay for Hepatitis C Virus Core Antigen in Japan

“…The World Health Organization (WHO) recently called for the elimination of HCV, aiming for a 90 reduction in prevalence and a 65 reduction in HCV-related mortality by 2030 (16). HCV RNA assays have been used in clinical practice due to their high specificity, sensitivity, and reproducibility; however, their cost restricts their use in some areas (10). Therefore, reliable, easy-to-use, and inexpensive assays are needed to detect HCV and confirm the success or failure of HCV eradication.…”

“…Since HCV infection is indicated by the presence of HCV RNA in serum, to detect its presence, an HCV RNA polymerase chain reaction (PCR) assay has been used in clinical practice due to its high sensitivity, specificity, and reproducibility (10). However, the HCV RNA assay is costly and the results are not available rapidly, making it unsuitable for use under some circumstances.…”