Generic sofosbuvir-based interferon-free direct acting antiviral agents for patients with chronic hepatitis C virus infection: a real-world multicenter observational study

Chen-Hua Liu,Jia-Horng Kao,Chien-Ching Hung,Sheng-Shun Yang,Hung-Chih Yang,Chun-Ming Hong,Tung-Hung Su,Wen-Chun Liu,Tai-Chung Tseng,Chung-Hsin Chang,Yi-Jie Huang,Sien-Sing Yang,Chun-Jen Liu,Ding-Shinn Chen,Pei-Jer Chen,Hsin-Yun Sun

doi:10.1038/s41598-018-32060-7

Abstract

Real-world data regarding the effectiveness and safety of generic sofosbuvir (SOF)-based interferon-free direct acting antiviral agents (DAAs) for patients with chronic hepatitis C virus (HCV) infection remain limited. A total of 517 chronic HCV-infected patients receiving 12 or 24 weeks of SOF-based therapies were retrospectively enrolled in 4 academic centers in Taiwan. The rate of sustained virologic response at week 12 off-therapy (SVR12) and that of treatment completion were assessed. The baseline characteristics and on-treatment HCV viral kinetics to predict SVR12 were analyzed. By evaluable population (EP) analysis, the SVR12 rate was 95.4% (95% confidence interval [CI]: 93.2–96.9%). The SVR12 was achieved in 29 of 34 patients (85.3%, 95% CI: 69.6–93.6%), 130 of 139 patients (93.5%, 95% CI: 88.2–96.6%), 119 of 124 patients (96.0%, 95% CI: 90.9–98.3%) and 215 of 220 patients (97.7%, 95% CI: 94.8–99.0%) who received SOF in combination with ribavirin (RBV), ledipasvir (LDV), daclatasvir (DCV) and velpatasvir (VEL), respectively. Of 517 patients, 514 (99.4%) completed the scheduled treatment. All 15 patients with true virologic failures were relapsers. Two decompensated cirrhotic patients had on-treatment deaths which were not related to DAAs. All 7 patients who were lost to follow-up had undetectable HCV RNA level at the last visit. The SVR12 rates were comparable in terms of baseline patient characteristics and viral decline at week 4 of treatment. In conclusion, generic SOF-based regimens are well tolerated and provide high SVR12 rates in patients with chronic HCV infection.

Highlights

Hepatitis C virus (HCV) infection remains a challenging health problem in the world
Patients were excluded from the study if they had a history of direct acting antiviral agents (DAAs) exposure, had estimated glomerular filtration rate
Of 593 HCV-infected patients receiving SOF-based IFN-free DAAs, 76 were excluded from the study because of prior DAA exposure, estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2, receiving antiviral regimens not recommended by guidelines, or refusal to provide informed consent

Summary

Introduction

Hepatitis C virus (HCV) infection remains a challenging health problem in the world. It is estimated that approximately 71.1 million people, which account for 1.0% of the world’s population, are HCV carriers[1]. The morbidity and mortality are significantly reduced once these patients achieve sustained virologic response (SVR) by anti-HCV agents[5,6,7,8,9]. The use of interferon (IFN)-free direct acting antiviral agents (DAAs) has made a paradigm shift and become the standard of care for HCV infection. SOF-based IFN-free DAAs are highly efficacious and well tolerated, many HCV-infected individuals have limited governmental reimbursement or private insurance support for brand-name agents[24,25,26]. Regarding the effectiveness and safety of generic SOF in combination with ledipasvir (LDV), daclatasvir (DCV), and/or RBV, several reports from China, India, Egypt and Argentina indicated that the SVR rates were >90% and most patients tolerated the treatment well[27,28,29,30,31]. On the basis of these encouraging results, we aimed to evaluate the performance of generic SOF-based DAAs for HCV and factors potentially affecting the treatment response in a multicenter cohort in Taiwan

Objectives

Methods

Results

Conclusion