Resistance-associated substitution and ledipasvir/sofosbuvir therapy in Mongolian chronic hepatitis C patients
Journal
Journal of the Formosan Medical Association
Journal Volume
119
Journal Issue
3
Pages
712-719
Date Issued
2020
Author(s)
Enkhzaya S.
Lin Y.-Y.
Khosbayar T.
Tsai C.-H.
Wang T.-S.
Enkhtuya D.
Ivshinkhorol D.
Naranzul N.
Jargalsaikhan B.
Amarsanaa J.
Baatarkhuu O.
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. ? 2019 Formosan Medical Association
Subjects
Chronic hepatitis C; Ledipasvir; Mongolia; Resistance-associated substitution; Sofosbuvir
SDGs
Other Subjects
alanine aminotransferase; ledipasvir plus sofosbuvir; nonstructural protein 5A; antivirus agent; benzimidazole derivative; fluorene derivative; ledipasvir; ledipasvir, sofosbuvir drug combination; sofosbuvir; uridine phosphate; adult; aged; alanine aminotransferase level; antiviral therapy; Article; chronic hepatitis C; clinical effectiveness; female; high throughput sequencing; human; major clinical study; male; Mongolia; prospective study; substitution therapy; sustained virologic response; treatment failure; treatment outcome; antiviral resistance; chronic hepatitis C; combination drug therapy; genetics; genotype; middle aged; Adult; Aged; Antiviral Agents; Benzimidazoles; Drug Resistance, Viral; Drug Therapy, Combination; Female; Fluorenes; Genotype; Hepatitis C, Chronic; High-Throughput Nucleotide Sequencing; Humans; Male; Middle Aged; Mongolia; Sofosbuvir; Treatment Failure; Treatment Outcome; Uridine Monophosphate
Publisher
Elsevier B.V.
Type
journal article