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Revisiting the Stopping Rule for Hepatitis C Genotype 1 Patients Treated with Peginterferon Plus Ribavirin
BACKGROUND: The current stopping rule for peginterferon/ribavirin therapy in hepatitis C virus genotype-1 (HCV-1) patients is based on an early virological response (EVR, defined as >2 log(10) viral reduction at treatment week 12). We aimed to explore rapid stopping rules at week 4. METHODS: We r...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528729/ https://www.ncbi.nlm.nih.gov/pubmed/23284866 http://dx.doi.org/10.1371/journal.pone.0052048 |
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author | Yu, Ming-Lung Liu, Chen-Hua Huang, Chung-Feng Tseng, Tai-Chung Huang, Jee-Fu Dai, Chia-Yen Lin, Zu-Yau Chen, Shinn-Cherng Wang, Liang-Yen Juo, Suh-Hang Hank Chuang, Wan-Long Kao, Jia-Horng |
author_facet | Yu, Ming-Lung Liu, Chen-Hua Huang, Chung-Feng Tseng, Tai-Chung Huang, Jee-Fu Dai, Chia-Yen Lin, Zu-Yau Chen, Shinn-Cherng Wang, Liang-Yen Juo, Suh-Hang Hank Chuang, Wan-Long Kao, Jia-Horng |
author_sort | Yu, Ming-Lung |
collection | PubMed |
description | BACKGROUND: The current stopping rule for peginterferon/ribavirin therapy in hepatitis C virus genotype-1 (HCV-1) patients is based on an early virological response (EVR, defined as >2 log(10) viral reduction at treatment week 12). We aimed to explore rapid stopping rules at week 4. METHODS: We randomly allocated 528 HCV-1 patients into training and validation sets (at a 1∶2 ratio). The interleukin-28B rs8099917 genotypes and on-treatment virological responses were evaluated to determine the negative predictive value (NPV) for achieving a sustained virological response (SVR, defined as undetectable HCV RNA 24 weeks after end-of-treatment). The study was approved by the ethics committees of the participating hospitals. All of the patients gave written informed consent before enrollment. RESULTS: A poor week 4 response (W4R), defined as a HCV RNA reduction of <1 log(10) IU/mL at week 4 or a week 4 HCV RNA>10,000 IU/mL with interleukin-28B non-TT genotype, had the highest NPV (95%). In the complete sample, poor W4R could identify 43.4% (59/136) of the non-responders, with an NPV of 95% and a false negative rate of only 0.8% (3/396). The multivariate analysis revealed that a poor W4R was the most important negative predictor (odds ratio/95% confidence intervals: 49.01/13.70–175.37), followed by the lack of an EVR. In addition to HCV RNA<1 log(10) IU/mL reduction, using the criteria of HCV RNA>10,000 IU/mL/non-TT genotype helped identifying an additional one-third of non-SVR patients at W4.Using the strategy of sequential rapid stopping rule strategy could identify 53.7% (73/136) of the non-responders (43.4% at week 4 and an addition 11.3% at week 12), as compared to 40.4% for the classical week-12 early stopping rule. CONCLUSIONS: Sequential rapid stopping rules using on-treatment virological responses and interleukin-28B genotype can rapidly identify additional peginterferon/ribavirin non-responders. |
format | Online Article Text |
id | pubmed-3528729 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35287292013-01-02 Revisiting the Stopping Rule for Hepatitis C Genotype 1 Patients Treated with Peginterferon Plus Ribavirin Yu, Ming-Lung Liu, Chen-Hua Huang, Chung-Feng Tseng, Tai-Chung Huang, Jee-Fu Dai, Chia-Yen Lin, Zu-Yau Chen, Shinn-Cherng Wang, Liang-Yen Juo, Suh-Hang Hank Chuang, Wan-Long Kao, Jia-Horng PLoS One Research Article BACKGROUND: The current stopping rule for peginterferon/ribavirin therapy in hepatitis C virus genotype-1 (HCV-1) patients is based on an early virological response (EVR, defined as >2 log(10) viral reduction at treatment week 12). We aimed to explore rapid stopping rules at week 4. METHODS: We randomly allocated 528 HCV-1 patients into training and validation sets (at a 1∶2 ratio). The interleukin-28B rs8099917 genotypes and on-treatment virological responses were evaluated to determine the negative predictive value (NPV) for achieving a sustained virological response (SVR, defined as undetectable HCV RNA 24 weeks after end-of-treatment). The study was approved by the ethics committees of the participating hospitals. All of the patients gave written informed consent before enrollment. RESULTS: A poor week 4 response (W4R), defined as a HCV RNA reduction of <1 log(10) IU/mL at week 4 or a week 4 HCV RNA>10,000 IU/mL with interleukin-28B non-TT genotype, had the highest NPV (95%). In the complete sample, poor W4R could identify 43.4% (59/136) of the non-responders, with an NPV of 95% and a false negative rate of only 0.8% (3/396). The multivariate analysis revealed that a poor W4R was the most important negative predictor (odds ratio/95% confidence intervals: 49.01/13.70–175.37), followed by the lack of an EVR. In addition to HCV RNA<1 log(10) IU/mL reduction, using the criteria of HCV RNA>10,000 IU/mL/non-TT genotype helped identifying an additional one-third of non-SVR patients at W4.Using the strategy of sequential rapid stopping rule strategy could identify 53.7% (73/136) of the non-responders (43.4% at week 4 and an addition 11.3% at week 12), as compared to 40.4% for the classical week-12 early stopping rule. CONCLUSIONS: Sequential rapid stopping rules using on-treatment virological responses and interleukin-28B genotype can rapidly identify additional peginterferon/ribavirin non-responders. Public Library of Science 2012-12-21 /pmc/articles/PMC3528729/ /pubmed/23284866 http://dx.doi.org/10.1371/journal.pone.0052048 Text en © 2012 Yu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Yu, Ming-Lung Liu, Chen-Hua Huang, Chung-Feng Tseng, Tai-Chung Huang, Jee-Fu Dai, Chia-Yen Lin, Zu-Yau Chen, Shinn-Cherng Wang, Liang-Yen Juo, Suh-Hang Hank Chuang, Wan-Long Kao, Jia-Horng Revisiting the Stopping Rule for Hepatitis C Genotype 1 Patients Treated with Peginterferon Plus Ribavirin |
title | Revisiting the Stopping Rule for Hepatitis C Genotype 1 Patients Treated with Peginterferon Plus Ribavirin |
title_full | Revisiting the Stopping Rule for Hepatitis C Genotype 1 Patients Treated with Peginterferon Plus Ribavirin |
title_fullStr | Revisiting the Stopping Rule for Hepatitis C Genotype 1 Patients Treated with Peginterferon Plus Ribavirin |
title_full_unstemmed | Revisiting the Stopping Rule for Hepatitis C Genotype 1 Patients Treated with Peginterferon Plus Ribavirin |
title_short | Revisiting the Stopping Rule for Hepatitis C Genotype 1 Patients Treated with Peginterferon Plus Ribavirin |
title_sort | revisiting the stopping rule for hepatitis c genotype 1 patients treated with peginterferon plus ribavirin |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528729/ https://www.ncbi.nlm.nih.gov/pubmed/23284866 http://dx.doi.org/10.1371/journal.pone.0052048 |
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