Drug Resistance Profile and Clinical Features for Hepatitis C Patients Experiencing DAA Failure in Taiwan

About 4% of the population in Taiwan are seropositive for anti-HCV Ab and 70% with HCV RNA. To address this high chronic hepatitis C disease load, Taiwan National Health Insurance started reimbursing genotype-specific DAAs in 2017 and pangenotype DAAs in mid-2018. With a 97% SVR12 rate, there were s...

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Autores principales:	Chun-Ming Hong, You-Yu Lin, Chun-Jen Liu, Ya-Yun Lai, Shiou-Hwei Yeh, Hung-Chih Yang, Jia-Horng Kao, Shih-Jer Hsu, Yi-Hsiang Huang, Sheng-Shun Yang, Hsing-Tao Kuo, Pin-Nan Cheng, Ming-Lung Yu, Pei-Jer Chen
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	direct-acting antiviral agent chronic hepatitis C treatment failure resistance-associated substitution whole genome sequencing Taiwan Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/4771619952644a0e85cb664e74106a9b
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spelling	oai:doaj.org-article:4771619952644a0e85cb664e74106a9b2021-11-25T19:14:16ZDrug Resistance Profile and Clinical Features for Hepatitis C Patients Experiencing DAA Failure in Taiwan10.3390/v131122941999-4915https://doaj.org/article/4771619952644a0e85cb664e74106a9b2021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4915/13/11/2294https://doaj.org/toc/1999-4915About 4% of the population in Taiwan are seropositive for anti-HCV Ab and 70% with HCV RNA. To address this high chronic hepatitis C disease load, Taiwan National Health Insurance started reimbursing genotype-specific DAAs in 2017 and pangenotype DAAs in mid-2018. With a 97% SVR12 rate, there were still 2–3% of patients that failed to clear HCV. To understand the causes of DAA failure in Taiwan, we conducted a multi-center, clinical, and virologic study. A total of 147 DAA-failure patients were recruited, and we searched HCV NS3/4A, NS5A and NS5B for known resistance-associated substitutions (RASs) by population sequencing, and conducted whole genome sequencing (WGS) for those without known RASs. A total of 107 patients received genotype-specific DAAs while 40 had pangenotype DAAs. Clinically, the important cause of failure is poor adherence. Virologically, common RASs in genotype-specific DAAs were NS5A-L31, NS5A-Y93, and NS5B-C316, while common RASs in pangenotype DAAs were NS5A-L31, NS5A-A/Q/R30, and NS5A-Y93. Additionally, new amino acid changes were found by WGS. Finally, we identified 12 cases with inconsistent baseline and post-treatment HCV genotypes, which is suggestive of re-infection rather than treatment failure. Our study described the drug resistance profile for DAA failure in Taiwan, showing differences from other countries.Chun-Ming HongYou-Yu LinChun-Jen LiuYa-Yun LaiShiou-Hwei YehHung-Chih YangJia-Horng KaoShih-Jer HsuYi-Hsiang HuangSheng-Shun YangHsing-Tao KuoPin-Nan ChengMing-Lung YuPei-Jer ChenMDPI AGarticledirect-acting antiviral agentchronic hepatitis Ctreatment failureresistance-associated substitutionwhole genome sequencingTaiwanMicrobiologyQR1-502ENViruses, Vol 13, Iss 2294, p 2294 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	direct-acting antiviral agent chronic hepatitis C treatment failure resistance-associated substitution whole genome sequencing Taiwan Microbiology QR1-502
spellingShingle	direct-acting antiviral agent chronic hepatitis C treatment failure resistance-associated substitution whole genome sequencing Taiwan Microbiology QR1-502 Chun-Ming Hong You-Yu Lin Chun-Jen Liu Ya-Yun Lai Shiou-Hwei Yeh Hung-Chih Yang Jia-Horng Kao Shih-Jer Hsu Yi-Hsiang Huang Sheng-Shun Yang Hsing-Tao Kuo Pin-Nan Cheng Ming-Lung Yu Pei-Jer Chen Drug Resistance Profile and Clinical Features for Hepatitis C Patients Experiencing DAA Failure in Taiwan
description	About 4% of the population in Taiwan are seropositive for anti-HCV Ab and 70% with HCV RNA. To address this high chronic hepatitis C disease load, Taiwan National Health Insurance started reimbursing genotype-specific DAAs in 2017 and pangenotype DAAs in mid-2018. With a 97% SVR12 rate, there were still 2–3% of patients that failed to clear HCV. To understand the causes of DAA failure in Taiwan, we conducted a multi-center, clinical, and virologic study. A total of 147 DAA-failure patients were recruited, and we searched HCV NS3/4A, NS5A and NS5B for known resistance-associated substitutions (RASs) by population sequencing, and conducted whole genome sequencing (WGS) for those without known RASs. A total of 107 patients received genotype-specific DAAs while 40 had pangenotype DAAs. Clinically, the important cause of failure is poor adherence. Virologically, common RASs in genotype-specific DAAs were NS5A-L31, NS5A-Y93, and NS5B-C316, while common RASs in pangenotype DAAs were NS5A-L31, NS5A-A/Q/R30, and NS5A-Y93. Additionally, new amino acid changes were found by WGS. Finally, we identified 12 cases with inconsistent baseline and post-treatment HCV genotypes, which is suggestive of re-infection rather than treatment failure. Our study described the drug resistance profile for DAA failure in Taiwan, showing differences from other countries.
format	article
author	Chun-Ming Hong You-Yu Lin Chun-Jen Liu Ya-Yun Lai Shiou-Hwei Yeh Hung-Chih Yang Jia-Horng Kao Shih-Jer Hsu Yi-Hsiang Huang Sheng-Shun Yang Hsing-Tao Kuo Pin-Nan Cheng Ming-Lung Yu Pei-Jer Chen
author_facet	Chun-Ming Hong You-Yu Lin Chun-Jen Liu Ya-Yun Lai Shiou-Hwei Yeh Hung-Chih Yang Jia-Horng Kao Shih-Jer Hsu Yi-Hsiang Huang Sheng-Shun Yang Hsing-Tao Kuo Pin-Nan Cheng Ming-Lung Yu Pei-Jer Chen
author_sort	Chun-Ming Hong
title	Drug Resistance Profile and Clinical Features for Hepatitis C Patients Experiencing DAA Failure in Taiwan
title_short	Drug Resistance Profile and Clinical Features for Hepatitis C Patients Experiencing DAA Failure in Taiwan
title_full	Drug Resistance Profile and Clinical Features for Hepatitis C Patients Experiencing DAA Failure in Taiwan
title_fullStr	Drug Resistance Profile and Clinical Features for Hepatitis C Patients Experiencing DAA Failure in Taiwan
title_full_unstemmed	Drug Resistance Profile and Clinical Features for Hepatitis C Patients Experiencing DAA Failure in Taiwan
title_sort	drug resistance profile and clinical features for hepatitis c patients experiencing daa failure in taiwan
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/4771619952644a0e85cb664e74106a9b
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Drug Resistance Profile and Clinical Features for Hepatitis C Patients Experiencing DAA Failure in Taiwan

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