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Performance of two HCV RNA assays during protease inhibitor-based triple therapy in patients with advanced liver fibrosis and cirrhosis.

Maasoumy B, Hunyady B, Calvaruso V, Makara M, Vermehren J, Haragh A, Susser S, Bremer B, Cloherty G, Manns MP, Craxì A, Wedemeyer H, Sarrazin C - PLoS ONE (2014)

Bottom Line: In patients with advanced liver disease an accurate risk/benefit calculation based on reliable HCV RNA results can reduce the number of adverse events.Discordance was also found for application of stopping rules.Importantly, only 4 of these patients failed to achieve SVR.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hanover, Germany.

ABSTRACT

Introduction: On-treatment HCV RNA measurements are crucial for the prediction of a sustained virological response (SVR) and to determine treatment futility during protease inhibitor-based triple therapies. In patients with advanced liver disease an accurate risk/benefit calculation based on reliable HCV RNA results can reduce the number of adverse events. However, the different available HCV RNA assays vary in their diagnostic performance.

Aim: To investigate the clinical relevance of concordant and discordant results of two HCV RNA assays during triple therapy with boceprevir and telaprevir in patients with advanced liver fibrosis/cirrhosis.

Methods: We collected on-treatment samples of 191 patients with advanced liver fibrosis/cirrhosis treated at four European centers for testing with the Abbott RealTime (ART) and COBAS AmpliPrep/COBAS TaqMan HCV v2.0 (CTM) assays.

Results: Discordant test results for HCV RNA detectability were observed in 23% at week 4, 17% at week 8/12 and 9% at week 24 on-treatment. The ART detected HCV RNA in 41% of week 4 samples tested negative by the CTM. However, the positive predictive value of an undetectable week 4 result for SVR was similar for both assays (80% and 82%). Discordance was also found for application of stopping rules. In 27% of patients who met stopping rules by CTM the ART measured levels below the respective cut-offs of 100 and 1000 IU/ml, respectively, which would have resulted in treatment continuation. In contrast, in nine patients with negative HCV RNA by CTM at week 24 treatment would have been discontinued due to detectable residual HCV RNA by the ART assay. Importantly, only 4 of these patients failed to achieve SVR.

Conclusion: Application of stopping rules determined in approval studies by one assay to other HCV RNA assays in clinical practice may lead to over and undertreatment in a significant number of patients undergoing protease inhibitor-based triple therapy.

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Related in: MedlinePlus

Correlation between the CTM and the ART in samples with quantifiable HCV RNA levels.r: Spearman correlation; p: p-value.
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pone-0110857-g002: Correlation between the CTM and the ART in samples with quantifiable HCV RNA levels.r: Spearman correlation; p: p-value.

Mentions: There were 56 samples available with quantifiable HCV RNA ≥50 IU/ml (range: 1.08–6.50 log IU/ml). Again, all samples were first tested with the CTM and afterwards retested with the ART. Correlation between the CTM and the ART was good in these samples (Spearman correlation: r = 0.9) (Figure 2). However, the CTM tended to yield higher levels compared with the ART. Overall, HCV RNA levels were higher with the CTM test in 91% of the samples. The mean log difference between the measured HCV RNA levels in both assays was 0.53 log IU/ml (range: 0.04–1.84 log IU/ml).


Performance of two HCV RNA assays during protease inhibitor-based triple therapy in patients with advanced liver fibrosis and cirrhosis.

Maasoumy B, Hunyady B, Calvaruso V, Makara M, Vermehren J, Haragh A, Susser S, Bremer B, Cloherty G, Manns MP, Craxì A, Wedemeyer H, Sarrazin C - PLoS ONE (2014)

Correlation between the CTM and the ART in samples with quantifiable HCV RNA levels.r: Spearman correlation; p: p-value.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4229112&req=5

pone-0110857-g002: Correlation between the CTM and the ART in samples with quantifiable HCV RNA levels.r: Spearman correlation; p: p-value.
Mentions: There were 56 samples available with quantifiable HCV RNA ≥50 IU/ml (range: 1.08–6.50 log IU/ml). Again, all samples were first tested with the CTM and afterwards retested with the ART. Correlation between the CTM and the ART was good in these samples (Spearman correlation: r = 0.9) (Figure 2). However, the CTM tended to yield higher levels compared with the ART. Overall, HCV RNA levels were higher with the CTM test in 91% of the samples. The mean log difference between the measured HCV RNA levels in both assays was 0.53 log IU/ml (range: 0.04–1.84 log IU/ml).

Bottom Line: In patients with advanced liver disease an accurate risk/benefit calculation based on reliable HCV RNA results can reduce the number of adverse events.Discordance was also found for application of stopping rules.Importantly, only 4 of these patients failed to achieve SVR.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hanover, Germany.

ABSTRACT

Introduction: On-treatment HCV RNA measurements are crucial for the prediction of a sustained virological response (SVR) and to determine treatment futility during protease inhibitor-based triple therapies. In patients with advanced liver disease an accurate risk/benefit calculation based on reliable HCV RNA results can reduce the number of adverse events. However, the different available HCV RNA assays vary in their diagnostic performance.

Aim: To investigate the clinical relevance of concordant and discordant results of two HCV RNA assays during triple therapy with boceprevir and telaprevir in patients with advanced liver fibrosis/cirrhosis.

Methods: We collected on-treatment samples of 191 patients with advanced liver fibrosis/cirrhosis treated at four European centers for testing with the Abbott RealTime (ART) and COBAS AmpliPrep/COBAS TaqMan HCV v2.0 (CTM) assays.

Results: Discordant test results for HCV RNA detectability were observed in 23% at week 4, 17% at week 8/12 and 9% at week 24 on-treatment. The ART detected HCV RNA in 41% of week 4 samples tested negative by the CTM. However, the positive predictive value of an undetectable week 4 result for SVR was similar for both assays (80% and 82%). Discordance was also found for application of stopping rules. In 27% of patients who met stopping rules by CTM the ART measured levels below the respective cut-offs of 100 and 1000 IU/ml, respectively, which would have resulted in treatment continuation. In contrast, in nine patients with negative HCV RNA by CTM at week 24 treatment would have been discontinued due to detectable residual HCV RNA by the ART assay. Importantly, only 4 of these patients failed to achieve SVR.

Conclusion: Application of stopping rules determined in approval studies by one assay to other HCV RNA assays in clinical practice may lead to over and undertreatment in a significant number of patients undergoing protease inhibitor-based triple therapy.

Show MeSH
Related in: MedlinePlus