Identifying cost-effective screening algorithms for active hepatitis C virus infections in a high prevalence setting

<p><b>Objective:</b> To evaluate the cost-effectiveness of different screening patterns for active chronic hepatitis C virus (HCV) infections utilizing the hepatitis C core antigen test compared to standard care in the context of a general screening program in a high-prevalence country.</p> <p><b>Methods:</b> This study developed a decision analytic model to estimate the cost-effectiveness of four screening algorithms for the detection of active HCV infections among asymptomatic individuals with an unknown HCV status in a context of high (>5%) HCV prevalence. Three algorithms started with a serological test for antibodies (AB) followed by a nucleic acid test for HCV-RNA (RNA), the HCVAg (AG) assay, or both. An additional single marker screening strategy with AG was added to the analysis. By the example of the Republic of Georgia, strategies were compared in terms of total costs for screening and diagnosis of an active infection from a health system perspective.</p> <p><b>Results:</b> Replacing RNA with AG for confirmation of positive AB identified fewer active infections (<b><i>–</i></b>110 per 100,000 screened subjects) at significantly reduced total costs (<b><i>–</i></b>$2.74 per screened) and costs per diagnosed infection (<b><i>–</i></b>$44). Adding a subsequent RNA confirmatory test on AG negative results captured at least the same rate compared to the standard (AB followed by RNA) at still reduced costs (<b><i>–</i></b>$1.16 per subject screened, <b><i>–</i></b>$22 per case detected). Utilizing AG as the frontline test revealed the highest detection rate (97.9%) at the highest costs (+$3.80 per subject, +$323 per case detected vs standard).</p> <p><b>Conclusion:</b> A combined pattern of HCV AB screening followed by sequential confirmation with AG and RNA on AG negatives would provide equal or better diagnostic performance at lower cost over a broad range of scenarios. Potential long-term consequences of screening strategies to patients and society have to be considered<b>,</b> since the latency period for HCV to develop into severe liver disease is long.</p

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

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

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

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

Flow chart of the inclusion and exclusion of IDEFICS/I.Family participants.

<p>Flow chart of the inclusion and exclusion of IDEFICS/I.Family participants.</p

Associations of fatty acids with systolic and diastolic blood pressure z-scores at baseline, after two years and after six years of follow-up stratified by BMI category¹.

<p>Associations of fatty acids with systolic and diastolic blood pressure z-scores at baseline, after two years and after six years of follow-up stratified by BMI category<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0165981#t003fn001" target="_blank">¹</a>.</p

Associations of fatty acids with systolic and diastolic blood pressure z-scores at baseline, after two years and after six years of follow-up stratified by sex¹.

<p>Associations of fatty acids with systolic and diastolic blood pressure z-scores at baseline, after two years and after six years of follow-up stratified by sex<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0165981#t004fn001" target="_blank">¹</a>.</p

Associations of polyunsaturated fatty acids with systolic and diastolic blood pressure z-scores at baseline, after 2 years and after 6 years of follow-up estimated based on fully adjusted mixed-effects models¹.

<p>Associations of polyunsaturated fatty acids with systolic and diastolic blood pressure z-scores at baseline, after 2 years and after 6 years of follow-up estimated based on fully adjusted mixed-effects models<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0165981#t002fn001" target="_blank">¹</a>.</p