Journal of the Formosan Medical Association = Taiwan yi zhi · 2019
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, Kao Jia-Horng
Аннотация
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.
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.