Goki Suda1, Atsushi Nagasaka2, Yoshiya Yamamoto3, Ken Furuya4, Kenichi Kumagai5, Mineo Kudo6, Katsumi Terashita1,7, Tomoe Kobayashi1,8, Izumi Tsunematsu9, Junichi Yoshida10, Takashi Meguro11, Megumi Kimura1, Jun Ito1, Machiko Umemura1, Takaaki Izumi1, Seiji Tsunematsu1, Fumiyuki Sato1, Yoko Tsukuda1,2, Masato Nakai1, Takuya Sho1, Mitsuteru Natsuizaka1, Kenichi Morikawa1, Koji Ogawa1, Naoya Sakamoto1. 1. Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan. 2. Department of Gastroenterology and Hepatology, Sapporo City General Hospital, Sapporo, Japan. 3. Department of Gastroenterology and Hepatology, Hakodate City General Hospital, Hakodate, Japan. 4. Department of Gastroenterology and Hepatology, JCHO Hokkaido Hospital, Sapporo, Japan. 5. Department of Gastroenterology and Hepatology, Hakodate Medical Association Hospital, Hakodate, Japan. 6. Department of Gastroenterology and Hepatology, Sapporo Hokuyu Hospital, Sapporo, Japan. 7. Department of Gastroenterology and Hepatology, Kushiro Rosai Hospital, Kushiro, Japan. 8. Department of Gastroenterology and Hepatology, Tomakomai City Hospital, Tomakomai, Japan. 9. Department of Gastroenterology and Hepatology, Touei Hospital, Sapporo, Japan. 10. Department of Gastroenterology and Hepatology, JCHO Sapporo Hokushin Hospital. 11. Department of Gastroenterology and Hepatology, Hokkaido Gastroenterology Hospital, Sapporo, Japan.
Abstract
AIM: Hepatitis C virus (HCV) infection is a risk factor for end-stage renal disease, renal graft failure, and hemodialysis patient mortality. However, the efficacy of direct-acting antiviral therapy for HCV-infected patients with renal impairment is unclear. Additionally, the promising NS5B inhibitor sofosbuvir has not been recommended for patients with severe renal impairment. In this prospective, multicenter study, we evaluated the efficacy and safety of daclatasvir and asunaprevir combination therapy, with a focus on patients with renal impairment. METHODS: The study included 322 genotype 1 HCV-infected patients who received daclatasvir and asunaprevir combination therapy. The safety and sustained virological response was examined at 12 weeks after the end of treatment and safety was evaluated according to renal function. RESULTS: Of 322 patients, 5% (16/322) and 2.5% (8/322) had chronic kidney disease stage G3b (estimated glomerular filtration rate [eGFR], 30-44 mL/min/1.73 m2 ) and stage G4/5 (eGFR, 15-29/<15 mL/min/1.73 m2 ), respectively. Baseline presence of the NS5A resistance-associated variant, previous simeprevir treatment, and HCV RNA titers, which were predictors of a sustained viral response, were similar between patients with eGFR <45 mL/min/1.73 m2 and eGFR >45 mL/min/1.73 m2 . Notably, the 12-week sustained viral response rate was comparable in patients with eGFR <45 mL/min/1.73 m2 (100%, 24/24) and those with eGFR >45 mL/min/1.73 m2 (88.9%, 265/298; P = 0.07). Treatment discontinuation rates and adverse events, including alanine aminotransferase elevation, anemia, and renal disorders, were similar between the two groups. CONCLUSION: Daclatasvir and asunaprevir combination therapy for patients with renal dysfunction was highly effective and safe.
AIM: Hepatitis C virus (HCV) infection is a risk factor for end-stage renal disease, renal graft failure, and hemodialysis patient mortality. However, the efficacy of direct-acting antiviral therapy for HCV-infectedpatients with renal impairment is unclear. Additionally, the promising NS5B inhibitor sofosbuvir has not been recommended for patients with severe renal impairment. In this prospective, multicenter study, we evaluated the efficacy and safety of daclatasvir and asunaprevir combination therapy, with a focus on patients with renal impairment. METHODS: The study included 322 genotype 1 HCV-infectedpatients who received daclatasvir and asunaprevir combination therapy. The safety and sustained virological response was examined at 12 weeks after the end of treatment and safety was evaluated according to renal function. RESULTS: Of 322 patients, 5% (16/322) and 2.5% (8/322) had chronic kidney disease stage G3b (estimated glomerular filtration rate [eGFR], 30-44 mL/min/1.73 m2 ) and stage G4/5 (eGFR, 15-29/<15 mL/min/1.73 m2 ), respectively. Baseline presence of the NS5A resistance-associated variant, previous simeprevir treatment, and HCV RNA titers, which were predictors of a sustained viral response, were similar between patients with eGFR <45 mL/min/1.73 m2 and eGFR >45 mL/min/1.73 m2 . Notably, the 12-week sustained viral response rate was comparable in patients with eGFR <45 mL/min/1.73 m2 (100%, 24/24) and those with eGFR >45 mL/min/1.73 m2 (88.9%, 265/298; P = 0.07). Treatment discontinuation rates and adverse events, including alanine aminotransferase elevation, anemia, and renal disorders, were similar between the two groups. CONCLUSION:Daclatasvir and asunaprevir combination therapy for patients with renal dysfunction was highly effective and safe.