Shih-Jer Hsu1, Sukhee Enkhzaya2, You-Yu Lin3, Tai-Chung Tseng4, Tulgaa Khosbayar5, Cheng-Hsueh Tsai6, Tzu-San Wang3, Damba Enkhtuya7, Dogsom Ivshinkhorol7, Nyamsuren Naranzul8, Badarch Jargalsaikhan9, Jazag Amarsanaa10, Oidov Baatarkhuu11, Jia-Horng Kao12. 1. Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan; Hepatology Medical Center, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan. 2. Department of Infectious Disease, School of Medicine, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia; Department of Comprehensive Laboratory, National Center for Communicable Diseases, Ulaanbaatar, Mongolia. 3. Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan. 4. Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan. 5. Department of Molecular Biology and Genetics, School of BioMedicine, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia. 6. Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan. 7. Happy Veritas Liver Diagnostic Center, Ulaanbaatar, Mongolia. 8. Department of Infectious Disease, School of Medicine, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia. 9. Department of Obstetrics and Gynecology, School of Medicine, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia. 10. Mongolian Association for the Study of Liver Diseases, Mongolia. 11. Department of Infectious Disease, School of Medicine, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia; Department of Comprehensive Laboratory, National Center for Communicable Diseases, Ulaanbaatar, Mongolia; Mongolian Association for the Study of Liver Diseases, Mongolia. Electronic address: baatarkhuu@mnums.edu.mn. 12. Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: kaojh@ntu.edu.tw.
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.
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 CHCpatients. 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 CHCpatients 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.