PMID- 32128704
OWN - NLM
STAT- MEDLINE
DCOM- 20210125
LR  - 20210125
IS  - 1936-0541 (Electronic)
IS  - 1936-0533 (Linking)
VI  - 14
IP  - 2
DP  - 2020 Mar
TI  - The effectiveness and safety of glecaprevir/pibrentasvir in chronic hepatitis C 
      patients with refractory factors in the real world: a comprehensive analysis of a 
      prospective multicenter study.
PG  - 225-238
LID - 10.1007/s12072-020-10019-z [doi]
AB  - BACKGROUND: Direct-acting anti-virals (DAAs) have markedly improved the 
      effectiveness of anti-viral therapy for chronic hepatitis C (CHC) patients. In a 
      phase III trial in Japan, treatment with the NS3/4A protease inhibitor 
      glecaprevir and the NS5A inhibitor pibrentasvir (G/P) resulted in a small number 
      of patients with refractory factors. We aimed to evaluate the effectiveness and 
      safety of G/P, especially among patients with these refractory factors, and the 
      influence of these factors on treatment. METHODS: In a prospective, multicenter 
      study involving 33 medical institutions, 1439 patients were treated with G/P, and 
      their efficacy, safety, and most frequent adverse effects (AEs) were analyzed. 
      RESULTS: Overall SVR12 rates were 99.1% (1397/1410) in the per-protocol-analysis, 
      and genotype sustained virologic response SVR12 rates were: genotype 1, 99.4% 
      (707/711); genotype 2, 99.4% (670/674); genotype 3, 80.0% (16/20). DAA-naive 
      patients (p = 0.008) with HCV genotype except 3 (genotype 1 vs. 3, 
      p = 2.68 x 10(-5); genotype 2 vs. 3, p = 3.28 x 10(-5)) had significantly higher 
      SVR12 rates. No significant difference was observed between CKD stage 1-3 (99.1% 
      [1209/1220]) and chronic kidney disease (CKD) stage 4-5 (98.9% [188/190]) 
      patients, or between cirrhotic (99.0% [398/402]) and non-cirrhotic (99.1% 
      [999/1008]) patients. Multiple logistic regression analysis revealed that 
      genotype 3 [OR 33.404, 95% CI (7.512-148.550), p value (p = 4.06 x 10(-5))] and 
      past experience of IFN-free DAAs [OR 3.977, 95% CI (1.153-13.725), p value 
      (p = 0.029)] were both significantly independent predictors of non-SVR12. AEs 
      were reported in 28.2% of patients, and 1.6% discontinued treatment owing to 
      drug-related AEs. AEs were significantly higher in CKD stage 4-5 (41.6% [79/190]) 
      than CKD stage 1-3 (26.1% [319/1220]) patients (p = 2.00 x 10(-5)). AEs were also 
      significantly higher in cirrhotic (38.6% [155/402]) than in non-cirrhotic (24.1% 
      [243/1008]) (p = 2.91 x 10(-18)) patients. CONCLUSIONS: G/P regimen is highly 
      effective and safe to treat CHC patients even with refractory factors such as CKD 
      and advanced liver fibrosis. However, patients with past experience of IFN-free 
      DAA treatment and genotype 3, CKD stage 4 or 5, and advanced liver fibrosis 
      should be more closely observed.
FAU - Nozaki, Akito
AU  - Nozaki A
AUID- ORCID: 0000-0002-3310-6632
AD  - Gastroenterological Center, Yokohama City University Medical Center, 4-57 
      Urafune-cho, Minami-ku, Yokohama, 232-0024, Japan. akino@yokohama-cu.ac.jp.
FAU - Atsukawa, Masanori
AU  - Atsukawa M
AD  - Department of Internal Medicine, Division of Gastroenterology and Hepatology, 
      Nippon Medical School, Tokyo, Japan.
FAU - Kondo, Chisa
AU  - Kondo C
AD  - Department of Internal Medicine, Division of Gastroenterology and Hepatology, 
      Nippon Medical School, Tokyo, Japan.
FAU - Toyoda, Hidenori
AU  - Toyoda H
AD  - Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan.
FAU - Chuma, Makoto
AU  - Chuma M
AD  - Gastroenterological Center, Yokohama City University Medical Center, 4-57 
      Urafune-cho, Minami-ku, Yokohama, 232-0024, Japan.
FAU - Nakamuta, Makoto
AU  - Nakamuta M
AD  - National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.
FAU - Uojima, Haruki
AU  - Uojima H
AD  - Department of Gastroenterology, Internal Medicine, Kitasato University School of 
      Medicine, Sagamihara, Japan.
FAU - Takaguchi, Koichi
AU  - Takaguchi K
AD  - Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan.
FAU - Ikeda, Hiroki
AU  - Ikeda H
AD  - Department of Internal Medicine, St. Marianna University School of Medicine, 
      Kawasaki, Japan.
FAU - Watanabe, Tsunamasa
AU  - Watanabe T
AD  - Department of Internal Medicine, St. Marianna University School of Medicine, 
      Kawasaki, Japan.
FAU - Ogawa, Shintaro
AU  - Ogawa S
AD  - Department of Virology and Liver Unit, Nagoya City University, Graduate School of 
      Medical Sciences, Aichi, Japan.
FAU - Itokawa, Norio
AU  - Itokawa N
AD  - Division of Gastroenterology, Department of Internal Medicine, Nippon Medical 
      School Chiba Hokusoh Hospital, Inzai, Japan.
FAU - Arai, Taeang
AU  - Arai T
AD  - Division of Gastroenterology, Department of Internal Medicine, Nippon Medical 
      School Musashikosugi Hospital, Kawasaki, Japan.
FAU - Hiraoka, Atsushi
AU  - Hiraoka A
AD  - Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan.
FAU - Asano, Toru
AU  - Asano T
AD  - Division of Gastroenterology and Hepatology, Department of Internal Medicine, 
      Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan.
FAU - Fujioka, Shinichi
AU  - Fujioka S
AD  - Department of Gastroenterology, Okayama Saiseikai General Hospital, Okayama, 
      Japan.
FAU - Ikegami, Tadashi
AU  - Ikegami T
AD  - Tokyo Medical University Ibaraki Medical Center, Ibaraki, Japan.
FAU - Shima, Toshihide
AU  - Shima T
AD  - Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, 
      Japan.
FAU - Ogawa, Chikara
AU  - Ogawa C
AD  - Department of Gastroenterology and Hepatology, Takamatsu Red Cross Hospital, 
      Takamatsu, Japan.
FAU - Akahane, Takehiro
AU  - Akahane T
AD  - Department of Gastroenterology, Japanese Red Cross Ishinomaki Hospital, 
      Ishinomaki, Japan.
FAU - Shimada, Noritomo
AU  - Shimada N
AD  - Division of Gastroenterology and Hepatology, Department of Internal Medicine, 
      Otakanomori Hospital, Kashiwa, Japan.
FAU - Fukunishi, Shinya
AU  - Fukunishi S
AD  - Second Department of Internal Medicine, Osaka Medical College, Osaka, Japan.
FAU - Abe, Hiroshi
AU  - Abe H
AD  - Division of Gastroenterology and Hepatology, Department of Internal Medicine, 
      Shinmatsudo Central General Hospital, Matsudo, Japan.
FAU - Tsubota, Akihito
AU  - Tsubota A
AD  - Core Research Facilities for Basic Science, The Jikei University School of 
      Medicine, Tokyo, Japan.
FAU - Genda, Takuya
AU  - Genda T
AD  - Department of Gastroenterology, Juntendo Shizuoka University Hospital, Shizuoka, 
      Japan.
FAU - Okubo, Hironao
AU  - Okubo H
AD  - Department of Gastroenterology, Juntendo Nerima University Hospital, Tokyo, 
      Japan.
FAU - Mikami, Shigeru
AU  - Mikami S
AD  - Division of Gastroenterology, Department of Internal Medicine, Kikkoman General 
      Hospital, Noda, Japan.
FAU - Morishita, Asahiro
AU  - Morishita A
AD  - Department of Gastroenterology, Kagawa University Graduate School of Medicine, 
      Kagawa, Japan.
FAU - Moriya, Akio
AU  - Moriya A
AD  - Department of Gastroenterology, Mitoyo General Hospital, Kannonji, Japan.
FAU - Tani, Joji
AU  - Tani J
AD  - Department of Internal Medicine, Yashima General Hospital, Takamatsu, Japan.
FAU - Tachi, Yoshihiko
AU  - Tachi Y
AD  - Bantane Hospital, Fujita Health University School of Medicine, Nagoya, Japan.
FAU - Hotta, Naoki
AU  - Hotta N
AD  - Division of Hepatology, Department of Internal Medicine, Masuko Memorial 
      Hospital, Nagoya, Japan.
FAU - Ishikawa, Toru
AU  - Ishikawa T
AD  - Department of Hepatology, Saiseikai Niigata Daini Hospital, Niigata, Japan.
FAU - Okanoue, Takeshi
AU  - Okanoue T
AD  - Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, 
      Japan.
FAU - Tanaka, Yasuhito
AU  - Tanaka Y
AD  - Department of Virology and Liver Unit, Nagoya City University, Graduate School of 
      Medical Sciences, Aichi, Japan.
FAU - Kumada, Takashi
AU  - Kumada T
AD  - Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan.
FAU - Iwakiri, Katsuhiko
AU  - Iwakiri K
AD  - Department of Internal Medicine, Division of Gastroenterology and Hepatology, 
      Nippon Medical School, Tokyo, Japan.
FAU - Maeda, Shin
AU  - Maeda S
AD  - Gastroenterological Center, Yokohama City University Medical Center, 4-57 
      Urafune-cho, Minami-ku, Yokohama, 232-0024, Japan.
AD  - Department of Gastroenterology, Yokohama City University Graduate School of 
      Medicine, Yokohama, Japan.
CN  - KTK49 Liver Study Group
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
DEP - 20200303
PL  - United States
TA  - Hepatol Int
JT  - Hepatology international
JID - 101304009
RN  - 0 (Antiviral Agents)
RN  - 0 (Benzimidazoles)
RN  - 0 (Drug Combinations)
RN  - 0 (Pyrrolidines)
RN  - 0 (Quinoxalines)
RN  - 0 (Sulfonamides)
RN  - 0 (glecaprevir and pibrentasvir)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antiviral Agents/administration & dosage/*therapeutic use
MH  - Benzimidazoles/administration & dosage/*therapeutic use
MH  - Drug Administration Schedule
MH  - Drug Combinations
MH  - Female
MH  - Hepatitis C, Chronic/blood/*drug therapy/virology
MH  - Humans
MH  - Japan
MH  - Male
MH  - Middle Aged
MH  - Prospective Studies
MH  - Pyrrolidines/administration & dosage/*therapeutic use
MH  - Quinoxalines/administration & dosage/*therapeutic use
MH  - Sulfonamides/administration & dosage/*therapeutic use
MH  - Sustained Virologic Response
MH  - Young Adult
OTO - NOTNLM
OT  - Chronic hepatitis C
OT  - Glecaprevir
OT  - Multicenter study
OT  - Pibrentasvir
OT  - Refractory factors
EDAT- 2020/03/05 06:00
MHDA- 2021/01/26 06:00
CRDT- 2020/03/05 06:00
PHST- 2019/09/18 00:00 [received]
PHST- 2020/01/28 00:00 [accepted]
PHST- 2020/03/05 06:00 [pubmed]
PHST- 2021/01/26 06:00 [medline]
PHST- 2020/03/05 06:00 [entrez]
AID - 10.1007/s12072-020-10019-z [pii]
AID - 10.1007/s12072-020-10019-z [doi]
PST - ppublish
SO  - Hepatol Int. 2020 Mar;14(2):225-238. doi: 10.1007/s12072-020-10019-z. Epub 2020 
      Mar 3.