Hepatitis C virus core antigen, an earlier and stronger predictor on sustained virological response in patients with genotype 1 HCV infection

Abstract

Background: Earlier kinetics of serum HCV core antigen (HCVcAg) and its predictive value on sustained virological response (SVR) were investigated in patients with genotype 1 HCV infection during antiviral treatment.

Methods: In a multi-centered, randomized and positive drug-controlled phase IIb clinical trial on type Y peginterferon α-2b ( NCT01140997), forty-eight CHC patients who participated in pharmacokinetics were randomly divided into 4 cohorts and treated with PegIFNα (type Y peginterferon α-2b 90 μg, 135 μg, 180 μg and PegIFNα-2a 180 μg, respectively, once a week) and ribavirin (< 75 kg, 1000 mg daily and ≥ 75 kg, 1200 mg daily) for 48 weeks, and then followed up for 24 weeks. 32 patients infected with genotype 1 HCV and completed the whole process were included in this study. HCV RNAs were detected at baseline, and weeks 4, 12, 24, 48 and 72 using Cobas TaqMan. ARCHITECT HCVcAg was performed at 24, 48, 72, 96, 120 and 144 h in addition to the above time points. The receiver operating curves (ROCs) were performed to study the predictive values of HCVcAg decline on SVR.

Results: Following antiviral treatment, serum HCVcAg levels rapidly declined within the first week and correlated well with corresponding HCV RNA at baseline, weeks 4, 12, 24, 48 and 72 (rs = 0.969, 0.928, 0.999, 0.983, 0.985 and 0.946, respectively, P < 0.001). All of the areas under the receiver operating curves (AUROCs) were more than 0.80 and showed good predictive power on SVR at 24, 48, 72, 96, 120 and 144 h. The144 h was the best predictive time point of HCVcAg decline on SVR because of its largest AUROC (more than 0.90).

Conclusions: Early kinetics of serum HCVcAg predicts SVR very well in genotype 1 CHC patients during antiviral treatment, and its reduction value at 144 h is an earlier and stronger predictor on SVR than rapid virological response and early virological response. (TRN: NCT01140997).

Figures

Figure 1

Dynamic changes of HCVcAg and HCV RNA levels during antiviral treatment. Following antiviral treatment, serum HCVcAg levels closely track those of HCV RNA and rapidly declined within the first 4 weeks.

Figure 2

ROCs of predictive values of ∆HCVcAg at various time points of the first 12 weeks on SVR. AUROCs calculated were 0.835, 0.814, 0.870, 0.866, 0.879, 0.913, 0.853, 0.823 and 0.719 at 24 h, 48 h, 72 h, 96 h, 120 h, 144 h, and weeks 4, 8, 12.

Figure 3

ROC curves of predictive values of HCV RNA at week 4 on sustained virological response (SVR). When the optimal cutoff value was 3.770, the corresponding AUROC was 0.854 (95% CI 0.705-1.000).

Figure 4

Influence of baseline parameters on ∆HCVcAg at 144 h. Decline of HCVcAg at 144 h showed a correlation with age (rs = -0.583, P < 0.001), and no correlation with baseline viral loads and HCVcAg levels (P = 0.107 and P = 0.288, respectively).