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

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.

• Authors: Shih-Jer Hsu, Sukhee Enkhzaya, You-Yu Lin, Tai-Chung Tseng, Tulgaa Khosbayar, Cheng-Hsueh Tsai, Tzu-San Wang, Damba Enkhtuya, Dogsom Ivshinkhorol, Nyamsuren Naranzul, Badarch Jargalsaikhan, Jazag Amarsanaa, Oidov Baatarkhuu, Jia-Horng Kao
• Journal: Journal of the Formosan Medical Association = Taiwan yi zhi (J Formos Med Assoc) Vol. 119 Issue 3 Pg. 712-719 (Mar 2020) ISSN: 0929-6646 [Print] Singapore
• PMID: 31672433 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.

Chemical References

• Antiviral Agents
• Benzimidazoles
• Fluorenes
• ledipasvir, sofosbuvir drug combination
• ledipasvir
• Uridine Monophosphate
• Sofosbuvir

Topics

• Adult
• Aged
• Antiviral Agents (therapeutic use)
• Benzimidazoles (therapeutic use)
• Drug Resistance, Viral (genetics)
• Drug Therapy, Combination
• Female
• Fluorenes (therapeutic use)
• Genotype
• Hepatitis C, Chronic (drug therapy, genetics)
• High-Throughput Nucleotide Sequencing
• Humans
• Male
• Middle Aged
• Mongolia
• Sofosbuvir (therapeutic use)
• Treatment Failure
• Treatment Outcome
• Uridine Monophosphate (analogs & derivatives)