Resistance-associated substitution and ledipasvir/sofosbuvir therapy in Mongolian chronic hepatitis C patients

• Published in: Journal of the Formosan Medical Association Vol. 119; no. 3; pp. 712 - 719
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Singapore Elsevier B.V 01.03.2020; Elsevier
• Subjects: Adult; Aged; Antiviral Agents - therapeutic use; Benzimidazoles - therapeutic use; Chronic hepatitis C; Drug Resistance, Viral - genetics; Drug Therapy, Combination; Female; Fluorenes - therapeutic use; Genotype; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - genetics; High-Throughput Nucleotide Sequencing; Humans; Ledipasvir; Male; Middle Aged; Mongolia; Resistance-associated substitution; Sofosbuvir; Sofosbuvir - therapeutic use; Treatment Failure; Treatment Outcome; Uridine Monophosphate - analogs & derivatives; Mongolia; Mongolia; Chronic hepatitis C; Resistance-associated substitution; Sofosbuvir; Ledipasvir
• ISSN: 0929-6646; 1876-0821
• DOI: 10.1016/j.jfma.2019.10.003

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. 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). 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). 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.