Monitoring the treatment of hepatitis C with directly acting antivirals by serological and molecular methods

<div><p>Aim</p><p>To evaluate the potential value of using a serological assay to quantitate the hepatitis C virus core antigen (HCV-Ag) when monitoring patients with chronic hepatitis C being treated with direct-acting antivirals (DAAs).</p><p>Methods</p><p>Ninety-six patients treated with DAAs, either alone (91) or in combination with PEG interferon (5), were tested for HCV-RNA and for HCV-Ag at baseline and at weeks 2, 4, 8 and 12 during treatment and 12 weeks after completion. The concordance and correlation between the viral parameters as well as the respective kinetics during and after treatment were evaluated.</p><p>Results</p><p>A sustained viral response (SVR) was achieved in 82 patients (91%), whereas 11 relapsed (R) and 1 showed a virological breakthrough while receiving treatment. HCV-RNA and HCV-Ag showed good concordance (kappa = 0.62) and correlation. No significant differences between SVR and R was observed in either assay at 2 and 4 weeks after the start of treatment. At 8 weeks, HCV-Ag showed higher accuracy than HCV-RNA (AUC: 0.74 vs. 0.55) and there was a significantly greater decrease from baseline in SVR than in R (4.01 vs. 3.36 log10; p<0.05).</p><p>Conclusions</p><p>Monitoring during treatment with DAAs by using either HCV-RNA or HCV-Ag has only a limited predictive value for SVR. Since those assays are equivalent for identifying a virological relapse, HCV-Ag may be preferred from an economical and organizational perspective.</p></div

Decrease (logarithmic mean values) from baseline levels of HCV-RNA and HCV-Ag during treatment; SVR = sustained viral response; RR = response with relapse; W2, W4, W8 = weeks 2, 4 and 8 after the start of treatment; * = p<0.05.

<p>W = weeks after the start of treatment.</p

Frequency of negative results for HCV-RNA (blue columns) and HCV-Ag (red columns) during on-treatment monitoring and follow-up of 96 patients treated with DAAs for chronic HCV-infection.

<p>Frequency of negative results for HCV-RNA (blue columns) and HCV-Ag (red columns) during on-treatment monitoring and follow-up of 96 patients treated with DAAs for chronic HCV-infection.</p

Qualitative comparison between HCV-RNA and HCV-Ag on 690 samples from 96 patients treated with DAAs.

<p>Qualitative comparison between HCV-RNA and HCV-Ag on 690 samples from 96 patients treated with DAAs.</p

Demographics, clinical and virological features and type of treatment of enrolled patients.

<p>Demographics, clinical and virological features and type of treatment of enrolled patients.</p

Univariate and logistic regression analysis linking failure with independent variables.

<p>Univariate and logistic regression analysis linking failure with independent variables.</p

Modifications of liver disease stage following DAA treatment in patients with cirrhosis.

<p>(A) Baseline, post-failure and post-retreatment SVR12 changes of Child Pugh Class; (B) baseline and post-failure changes of Child Pugh Class for patients who were not retreated yet; (C) baseline and post-SVR12 changes of Child Pugh Class for patients who achieved SVR12 following the first DAA treatment. Bold arrows indicate patients who did not change the Child Pugh Class. Dashed arrows indicate patients who worsened the Child Pugh Class, whereas the grey arrows indicate patients who improved the Child Pugh class. In the curly brackets are reported the number of patients for specific changes observed in the Child Pugh classes in the three points of evaluation. n = number of patients.</p

Characteristics of the study patients according to SVR following the first DAA treatment.

<p>Characteristics of the study patients according to SVR following the first DAA treatment.</p

Failure rates following the first DAA regimen, by HCV genotype and treatment regimen in patients who completed the 12 weeks post treatment evaluation (n = 3,830 patients).

<p>Failure rates following the first DAA regimen, by HCV genotype and treatment regimen in patients who completed the 12 weeks post treatment evaluation (n = 3,830 patients).</p