Longitudinal assessment of HCV core antigen kinetics to monitor therapeutic response in the age of DAAs.

BACKGROUND: In the economy of therapeutic monitoring, an affordable viral marker is essential in the era of direct-acting antivirals (DAAs). We elucidated the kinetics of HCVcAg to delineate its precise role in monitoring therapeutic response. METHODS: In this longitudinal study, 3208 patients were tested for HCV RNA. A total of 423 patients were started on DAAs. Treatment response and kinetics of HCVcAg/RNA were assessed in treatment-naïve (n = 383) and previously treated (n = 40) patients with follow-up for 2 years. RESULTS: After the initiation of DAAs, the rate of relapse was significantly higher in the previously treated group than naive group [12.5% (5/40) Vs 2% (7/383), p<0.0001]. The response rate at RVR was significantly higher with HCVcAg than RNA in both groups (p<0.02). The kinetics of HCVcAg and RNA were significantly different at ETR and SVR12 in the naïve (p<0.04), but similar at all therapeutic points in the previously treated group. The correlation between HCVcAg and RNA was good at baseline, ETR and SVR, except RVR in both groups (r>0.6; p<0.0001). Furthermore, HCV genotypes, treatment regimen, CTP (<7/≥7) and MELD (<15/≥15) did not influence the therapeutic response and the viral replication kinetics (p>0.05). CONCLUSIONS: It is the first longitudinal study from India shows that the response rate and kinetics of HCVcAg are comparable to HCV RNA for an extended duration, except at RVR, irrespective of the HCV genotypes, treatment regimen, and liver disease severity. Hence, HCVcAg can be considered as a pragmatic marker to monitor therapeutic response and predict relapse in the era of DAAs.

Cost-Effective In-House Neutralization Assay for the Confirmation of HBeAg.

BACKGROUND & AIM: Hepatitis B virus-e-antigen (HBeAg) is an affordable viral marker to assess viral replication kinetics and response to antiviral therapy. In the absence of confirmatory assays, discrepant or false-positive HBeAg results are resolved by screening for other HBV markers. We standardized an in-house HBeAg neutralization assay (HBeAg-NT) to confirm HBeAg in clinical samples. METHODS: The performance and reliability of this assay were evaluated by first WHO International Standard for HBeAg (first WHO-IS HBeAg) from Paul Ehrlich Institute and clinical samples (n = 150) from chronic HBV carriers. Of these, 71 HBeAg-positive sera were used for HBeAg-NT. RESULTS: Concentrations spanning 0.25-10 U of first WHO-IS HBeAg and clinical samples (S/Co ranges from 1.00 to 10.00) were neutralized completely in the HBeAg-NT. CONCLUSIONS: HBeAg-NT is a simple, cost-effective, and reliable direct approach to confirm HBeAg in clinical samples which precludes the need for screening additional HBV markers in low resource settings.