1. Resistance-associated substitution and ledipasvir/sofosbuvir therapy in Mongolian chronic hepatitis C patients.
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Hsu, Shih-Jer, Enkhzaya, Sukhee, Lin, You-Yu, Tseng, Tai-Chung, Khosbayar, Tulgaa, Tsai, Cheng-Hsueh, Wang, Tzu-San, Enkhtuya, Damba, Ivshinkhorol, Dogsom, Naranzul, Nyamsuren, Jargalsaikhan, Badarch, Amarsanaa, Jazag, Baatarkhuu, Oidov, and Kao, Jia-Horng
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CHRONIC hepatitis C ,ALANINE aminotransferase ,HEPATITIS C virus ,TREATMENT effectiveness ,NUCLEOTIDE sequencing - Abstract
Background: Mongolia has the highest prevalence of hepatitis C virus (HCV) infection worldwide. Ledipasvir/sofosbuvir (LDV/SOF) was introduced to Mongolia since 2016 for HCV eradication. It has been reported that HCV resistance-associated substitutions (RASs) would affect the effectiveness of LDV/SOF in western chronic hepatitis C (CHC) patients. We thus investigated the effectiveness of LDV/SOF and the impact of RAS on the treatment outcome in Mongolian CHC patients.Methods: Patients with genotype (GT) 1b HCV infection were prospectively enrolled in Mongolia and treated with LDV/SOF for 12 weeks. The proportion of pre-treatment NS5A Y93H RAS in viral quasispecies was measured with next-generation sequencing. The endpoint of LDV/SOF effectiveness was sustained virological response at post-treatment week 12 (SVR12).Results: A total of 94 CHC patients were evaluated. The baseline Y93H proportion was <1% in 74 patients, 1-15% in 7, 15-50% in 2, and ≥50% in 11. All patients completed 12-week LDV/SOF treatment and the SVR rate was 90.4%. The rate of failure to achieve SVR12 for patients with Y93H < 1%, 1-15%, and ≥15% were 0%, 14.3%, and 61.5%, respectively (p for trend = 0.001). In univariable analysis, older age, baseline alanine transaminase level <40 U/mL, and a higher proportion of Y93H were associated with treatment failure. In multivariable analysis, only a higher proportion of Y93H was associated with treatment failure (p = 0.022).Conclusion: LDV/SOF therapy achieves a high SVR rate in Mongolian CHC GT1b patients without baseline Y93H RAS. A higher proportion of Y93H may severely undermine the effectiveness of LDV/SOF. [ABSTRACT FROM AUTHOR]- Published
- 2020
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