The efficacy and safety of dual oral therapy with daclatasvir and asunaprevir for genotype 1b in Japanese real-life settings.
It is important to investigate the treatment outcomes in patients excluded from clinical trials (CTR). The aims of this study were to evaluate the efficacy and safety of a 24-week daclatasvir (DCV) and asunaprevir (ASV) therapy for patients with chronic hepatitis C virus (HCV)-1b infection.



A total of 651 HCV-1b patients started dual oral therapy with DCV and ASV for 24 weeks in Toranomon Hospital, Tokyo. Among them, 276 patients met phase III CTR inclusion criteria. The sustained virological response (SVR) rate after treatment and the adverse events during therapy were compared between CTR-met (patients who met the inclusion criteria) and CTR-unmet (patients who did not meet the inclusion criteria) groups.



SVR12 was achieved in 87.0% (240/276) and 86.7% (325/375) in CTR-met and CTR-unmet patients respectively. SVR12 rate in simeprevir-experienced patients was 52.9% (9/17). SVR12 rate in patients without resistance-associated variant (RAV) of NS3 or NS5A loci was 93.7% (416/444). However, the SVR12 rates in patients with NS3-D168, NS5A-L31 and Y93 single RAV at baseline were 55.0% (11/20), 73.9% (17/23) and 65.6% (63/96) respectively. The safety profiles in both CTR-met and CTR-unmet patients were similar. The discontinuation rate as a result of alanine aminotransferase (ALT) elevation was only 2.9%. Seven (2.5%) patients in CTR-met group and 20 (5.3%) in CTR-unmet group discontinued therapy because of adverse events other than the ALT elevation.



Dual oral therapy with DCV and ASV in real-life settings was well tolerated with a similar safety profile and achieved similar SVR12 rates as that of CTR.
Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
Hitomi
0000-0002-4282-0934
H
Sezaki
Department of Hepatology, Toranomon Hospital, Tokyo, Japan.|Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
Fumitaka
F
Suzuki
Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
Tetsuya
T
Hosaka
Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
Norio
N
Akuta
Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
Shunichiro
S
Fujiyama
Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
Yusuke
Y
Kawamura
Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
Masahiro
M
Kobayashi
Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
Yoshiyuki
Y
Suzuki
Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
Satoshi
S
Saitoh
Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
Yasuji
Y
Arase
Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
Kenji
K
Ikeda
Research Institute for Hepatology, Toranomon Hospital, Tokyo, Japan.
Mariko
M
Kobayashi
Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
Hiromitsu
H
Kumada
D000284:Administration, Oral; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002219:Carbamates; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D007546:Isoquinolines / Q000008:administration & dosage* / Q000009:adverse effects; D007564:Japan; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines; D012367:RNA, Viral / Q000097:blood; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects; D000072230:Sustained Virologic Response; D014633:Valine / Q000031:analogs & derivatives; D017361:Viral Nonstructural Proteins / Q000235:genetics
D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D007546:Isoquinolines; D011759:Pyrrolidines; D012367:RNA, Viral; D013449:Sulfonamides; D017361:Viral Nonstructural Proteins; D000410:Alanine Transaminase; D014633:Valine; C549273:daclatasvir; C571889:asunaprevir
asunaprevir; daclatasvir; hepatitis C virus; resistance-associated variant