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.

Fig 1. Frequencies of the rs12979860 CC genotype for PI therapies and association with treatment outcome.

Fig 2

Scatter plots depicting the correlation between HCV RNA (log₁₀ IU/ml) and HCVcAg (log₁₀ fmol/l) measurements in samples from the cohorts receiving TVR (A) and BOC (B) at early time points. The lower left hand corner restricted by the dashed lines indicates the area where both RNA and antigen are not detected by the respective assays.

Fig 3

Algorithm for identifying CHC patients receiving TVR (A) and BOC (B) with an increased likelihood to achieve SVR by combining pre-treatment and on-treatment factors.