PMID- 30903385
OWN - NLM
STAT- MEDLINE
DCOM- 20200721
LR  - 20210109
IS  - 1435-5922 (Electronic)
IS  - 0944-1174 (Linking)
VI  - 54
IP  - 10
DP  - 2019 Oct
TI  - Initial- and re-treatment effectiveness of glecaprevir and pibrentasvir for 
      Japanese patients with chronic hepatitis C virus-genotype 1/2/3 infections.
PG  - 916-927
LID - 10.1007/s00535-019-01575-9 [doi]
AB  - BACKGROUND: Glecaprevir and pibrentasvir (GLE/PIB) are potent antiviral agents 
      for hepatitis C virus (HCV) pan-genotypic infections; however, their clinical 
      effectiveness and safety remain limited in the real-world. This study aimed to 
      evaluate viral responses and the safety of GLE/PIB for patients with chronic 
      HCV-1/2/3 infections during both initial- (Arm A) and re-treatment (Arm B) with 
      all-oral direct-acting antiviral agents (DAAs). METHODS: This 
      prospective-observational cohort study included Japanese patients with chronic 
      HCV-1/2/3 infections (n = 271: 183 in Arm A and 83 in Arm B), who had started 
      receiving GLE/PIB. Primary end point was a sustained virological response (SVR) 
      rate at week 12 (SVR12) after the end of GLE/PIB treatment (EOT). RESULTS: SVR12 
      was achieved by 99.4% of patients (180/181: modified intention-to-treat (mITT) 
      analysis excluding 2 patients lost to follow-up) in Arm A. One patient with an 
      HCV-3b infection who discontinued at week 8 failed to achieve SVR12. SVR12 was 
      achieved by 97.7% of patients (85/87: mITT excluding 1 patient lost to follow-up) 
      in Arm B. Virological relapse occurred in 2 patients with HCV-1b, presenting 
      common 5 loci of resistance-associated substitutions (RASs) including A92 RASs in 
      the NS5A lesion at baseline. Any adverse events (AEs) (grade >/= 3) occurred in 8 
      patients (3.0%). 8 patients (3.0%) discontinued due to AEs, however, all of them 
      achieved SVR12. CONCLUSIONS: Initial and re-treatment with GLE/PIB are effective 
      and safe for Japanese patients with HCV-1/2/3 in real-life settings. Further 
      studies are required to elucidate the mechanism underlying treatment failures of 
      GLE/PIB to completely eradicate HCV worldwide.
FAU - Sezaki, Hitomi
AU  - Sezaki H
AUID- ORCID: 0000-0002-4282-0934
AD  - Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 
      105-8470, Japan. hitomis@mx1.harmonix.ne.jp.
FAU - Suzuki, Fumitaka
AU  - Suzuki F
AD  - Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 
      105-8470, Japan.
FAU - Hosaka, Tetsuya
AU  - Hosaka T
AD  - Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 
      105-8470, Japan.
FAU - Fujiyama, Shunichirou
AU  - Fujiyama S
AD  - Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 
      105-8470, Japan.
FAU - Kawamura, Yusuke
AU  - Kawamura Y
AD  - Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 
      105-8470, Japan.
FAU - Akuta, Norio
AU  - Akuta N
AD  - Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 
      105-8470, Japan.
FAU - Kobayashi, Masahiro
AU  - Kobayashi M
AD  - Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 
      105-8470, Japan.
FAU - Suzuki, Yoshiyuki
AU  - Suzuki Y
AD  - Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 
      105-8470, Japan.
FAU - Saitoh, Satoshi
AU  - Saitoh S
AD  - Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 
      105-8470, Japan.
FAU - Arase, Yasuji
AU  - Arase Y
AD  - Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 
      105-8470, Japan.
FAU - Ikeda, Kenji
AU  - Ikeda K
AD  - Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 
      105-8470, Japan.
FAU - Kobayashi, Mariko
AU  - Kobayashi M
AD  - Research Institute for Hepatology, Toranomon Hospital, Tokyo, Japan.
FAU - Kumada, Hiromitsu
AU  - Kumada H
AD  - Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 
      105-8470, Japan.
LA  - eng
PT  - Journal Article
PT  - Observational Study
DEP - 20190322
PL  - Japan
TA  - J Gastroenterol
JT  - Journal of gastroenterology
JID - 9430794
RN  - 0 (Antiviral Agents)
RN  - 0 (Benzimidazoles)
RN  - 0 (Drug Combinations)
RN  - 0 (Pyrrolidines)
RN  - 0 (Quinoxalines)
RN  - 0 (RNA, Viral)
RN  - 0 (Sulfonamides)
RN  - 0 (glecaprevir and pibrentasvir)
SB  - IM
MH  - Aged
MH  - Antiviral Agents/administration & dosage/adverse effects/*therapeutic use
MH  - Benzimidazoles/administration & dosage/adverse effects/*therapeutic use
MH  - Drug Administration Schedule
MH  - Drug Combinations
MH  - Drug Resistance, Viral
MH  - Female
MH  - Hepacivirus/drug effects/*genetics
MH  - Hepatitis C, Chronic/complications/*drug therapy/virology
MH  - Humans
MH  - Liver Cirrhosis/virology
MH  - Male
MH  - Middle Aged
MH  - Prospective Studies
MH  - Pyrrolidines/administration & dosage/adverse effects/*therapeutic use
MH  - Quinoxalines/administration & dosage/adverse effects/*therapeutic use
MH  - RNA, Viral/blood
MH  - Retreatment/adverse effects/methods
MH  - Sulfonamides/administration & dosage/adverse effects/*therapeutic use
MH  - Sustained Virologic Response
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Direct-acting antiviral agents
OT  - Glecaprevir
OT  - Pibrentasvir
OT  - Resistance-associated substitutions
OT  - Sustained viral response
EDAT- 2019/03/25 06:00
MHDA- 2020/07/22 06:00
CRDT- 2019/03/24 06:00
PHST- 2019/01/29 00:00 [received]
PHST- 2019/03/17 00:00 [accepted]
PHST- 2019/03/25 06:00 [pubmed]
PHST- 2020/07/22 06:00 [medline]
PHST- 2019/03/24 06:00 [entrez]
AID - 10.1007/s00535-019-01575-9 [pii]
AID - 10.1007/s00535-019-01575-9 [doi]
PST - ppublish
SO  - J Gastroenterol. 2019 Oct;54(10):916-927. doi: 10.1007/s00535-019-01575-9. Epub 
      2019 Mar 22.