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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
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.
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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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