Predictors for HCV treatment outcome: lower limit of quantification vs. limit of detection

Abstract

Introduction. In HCV treatment, the early on-treatment virological status is used as guideline for response guided therapy (RGT) and is the key predictor for a sustained virological response (SVR). The response to treatment (RT) is determined by HCV RNA results at week 4 and 12 of treatment. Being ‘undetectable’ at these time points, is a reliable predictor for reaching a SVR. To define an ‘undetectable’ HCV RNA, the lower limit of quantification (LOQ) and not the limit of detection (LOD) is used. This leaves a gray zone between the LOQ and the LOD, which results in a ‘detectable but no quantifiable’ (DNQ) HCV RNA to be reported as ‘undetectable’. The aim of this study is to analyse the reliability of using the LOQ at key decision time points, week 4 (Rapid viral response; RVR) and week 12 ( Early viral response; EVR) to predict treatment outcome. Methods. Retrospective analysis of the response to therapy, treatment outcome and SVR of patients treated for HCV. In the period Oct 2012 – Apr 2013, HCV RNA samples were conducted at week 4, 12, end of treatment (EOT) and 24 weeks after treatment and tested with the Ampliprep/Cobas-Taqman_HCV-test-v1.0. (Limit of detection; LOD: 15 IU/ml, Lower limit of quantification; LOQ: 43 IU/ml). Results. In total, 19 patients were treated, of which 10 relapsed and 9 cleared the virus. In both treatment outcome groups, DNQ HCV RNA statuses were observed. Treatment outcome showed no relation between having a DNQ during treatment (p=0,350) or at decision time points, 4th week (p=0,167) or 12th week (p=0,474). In contrast, a on-treatment viral status >LOQ and <LOD showed a relation with treatment outcome at week 4 (p=0,007), but not at week 12 (p=0,474). In addition, the response to therapy (RVR or EVR) showed a relation with reaching SVR (p=0,023), which was not influenced by the on-treatment viral status; DNQ. Conclusion. Reaching an ‘undetectable’ HCV RNA result at week 4 and/or week 12, is not always a guarantee of achieving SVR. In our study, being ‘detectable but not quantifiable’ at decision time point does not give a higher incidence of relapsing. The HCV RNA being ‘detectable but not quantifiable’ does not influence the predictive value of a Rapid or Early viral response. Therefore, our study suggests that no alterations in the decision-rules for HCV guidelines have to be carried out.