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© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

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.

Details

Title
Drug Resistance Profile and Clinical Features for Hepatitis C Patients Experiencing DAA Failure in Taiwan
Author
Chun-Ming, Hong 1   VIAFID ORCID Logo  ; You-Yu, Lin 2 ; Liu, Chun-Jen 3 ; Ya-Yun, Lai 4 ; Yeh, Shiou-Hwei 5 ; Yang, Hung-Chih 6 ; Jia-Horng Kao 3   VIAFID ORCID Logo  ; Hsu, Shih-Jer 7 ; Yi-Hsiang, Huang 8   VIAFID ORCID Logo  ; Sheng-Shun, Yang 9 ; Hsing-Tao Kuo 10 ; Pin-Nan Cheng 11 ; Ming-Lung, Yu 12   VIAFID ORCID Logo  ; Chen, Pei-Jer 3   VIAFID ORCID Logo 

 Division of Hospital Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei 10022, Taiwan; [email protected] 
 Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan; [email protected] (Y.-Y.L.); [email protected] (C.-J.L.); [email protected] (J.-H.K.) 
 Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan; [email protected] (Y.-Y.L.); [email protected] (C.-J.L.); [email protected] (J.-H.K.); Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei 10022, Taiwan; [email protected] (H.-C.Y.); [email protected] (S.-J.H.) 
 Center of Precision Medicine, National Taiwan University, Taipei 10055, Taiwan; [email protected] (Y.-Y.L.); [email protected] (S.-H.Y.) 
 Center of Precision Medicine, National Taiwan University, Taipei 10055, Taiwan; [email protected] (Y.-Y.L.); [email protected] (S.-H.Y.); Graduate Institute of Microbiology, National Taiwan University College of Medicine, National Taiwan University, Taipei 10051, Taiwan 
 Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei 10022, Taiwan; [email protected] (H.-C.Y.); [email protected] (S.-J.H.) 
 Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei 10022, Taiwan; [email protected] (H.-C.Y.); [email protected] (S.-J.H.); Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin 64000, Taiwan 
 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan; [email protected]; Institute of Clinical Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei 11230, Taiwan 
 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan; [email protected] 
10  Chi Mei Medical Center, Department of Internal Medicine, Tainan 71004, Taiwan; [email protected] 
11  Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 70403, Taiwan; [email protected] 
12  Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80756, Taiwan 
First page
2294
Publication year
2021
Publication date
2021
Publisher
MDPI AG
e-ISSN
19994915
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2602242953
Copyright
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.