https://scholars.lib.ntu.edu.tw/handle/123456789/623059
Title: | Drug Resistance Profile and Clinical Features for Hepatitis C Patients Experiencing DAA Failure in Taiwan | Authors: | CHUN-MING HONG Lin, You-Yu CHUN-JEN LIU Lai, Ya-Yun Shiou-Hwei Yeh HUNG-CHIH YANG JIA-HORNG KAO SHIH-JER HSU Huang, Yi-Hsiang Yang, Sheng-Shun Kuo, Hsing-Tao Cheng, Pin-Nan Yu, Ming-Lung PEI-JER CHEN |
Keywords: | Taiwan; chronic hepatitis C; direct-acting antiviral agent; resistance-associated substitution; treatment failure; whole genome sequencing | Issue Date: | Nov-2021 | Publisher: | MDPI | Journal Volume: | 13 | Journal Issue: | 11 | Start page/Pages: | 2294 | Source: | Viruses | 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. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/623059 | ISSN: | 1999-4915 | DOI: | 10.3390/v13112294 |
Appears in Collections: | 醫學系 |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.