PMID- 30203225
OWN - NLM
STAT- MEDLINE
DCOM- 20191206
LR  - 20211010
IS  - 1435-5922 (Electronic)
IS  - 0944-1174 (Print)
IS  - 0944-1174 (Linking)
VI  - 54
IP  - 1
DP  - 2019 Jan
TI  - Efficacy and safety of sofosbuvir-velpatasvir with or without ribavirin in 
      HCV-infected Japanese patients with decompensated cirrhosis: an open-label phase 
      3 trial.
PG  - 87-95
LID - 10.1007/s00535-018-1503-x [doi]
AB  - BACKGROUND: In Japan, hepatitis C virus (HCV)-infected patients with 
      decompensated cirrhosis currently have no treatment options. In this Phase 3 
      study, we evaluated sofosbuvir-velpatasvir with or without ribavirin for 12 weeks 
      in patients with any HCV genotype and decompensated cirrhosis 
      [Child-Pugh-Turcotte (CPT) class B or C] in Japan. METHODS: Patients were 
      randomized 1:1 to receive sofosbuvir-velpatasvir with or without ribavirin for 
      12 weeks. Randomization was stratified by CPT class and genotype. Sustained 
      virologic response 12 weeks following completion of treatment (SVR12) was the 
      primary efficacy endpoint. RESULTS: Of the 102 patients enrolled, 57% were 
      treatment naive, 78% and 20% had genotype 1 and 2 HCV infection, respectively, 
      and 77% and 20% had CPT class B and C cirrhosis, respectively, at baseline. 
      Overall, 61% of patients were female and the mean age was 66 years (range 41-83). 
      SVR12 rates were 92% (47/51) in each group. Among patients who achieved SVR12, 
      26% had improved CPT class from baseline to posttreatment week 12. Most adverse 
      events (AEs) were consistent with clinical sequelae of advanced liver disease or 
      known toxicities of ribavirin. Four patients (8%) who received 
      sofosbuvir-velpatasvir and seven (14%) who received sofosbuvir-velpatasvir plus 
      ribavirin experienced a serious AE. The 3 deaths (bacterial sepsis, gastric 
      varices hemorrhage, hepatocellular carcinoma) were attributed to liver disease 
      progression. CONCLUSION: Sofosbuvir-velpatasvir for 12 weeks provides a highly 
      effective and well-tolerated therapy for Japanese patients with HCV and 
      decompensated cirrhosis. Ribavirin did not improve efficacy but increased 
      toxicity.
FAU - Takehara, Tetsuo
AU  - Takehara T
AUID- ORCID: 0000-0001-5036-3457
AD  - Osaka University, 2-15 Yamadaoka, Suita, Osaka, 565-0871, Japan. 
      takehara@gh.med.osaka-u.ac.jp.
FAU - Sakamoto, Naoya
AU  - Sakamoto N
AD  - Hokkaido University, Sapporo, Hokkaido, Japan.
FAU - Nishiguchi, Shuhei
AU  - Nishiguchi S
AD  - Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
FAU - Ikeda, Fusao
AU  - Ikeda F
AD  - Okayama University, Okayama, Japan.
FAU - Tatsumi, Tomohide
AU  - Tatsumi T
AD  - Osaka University, 2-15 Yamadaoka, Suita, Osaka, 565-0871, Japan.
FAU - Ueno, Yoshiyuki
AU  - Ueno Y
AD  - Yamagata University, Yamagata, Japan.
FAU - Yatsuhashi, Hiroshi
AU  - Yatsuhashi H
AD  - Nagasaki Medical Center, Nagasaki, Japan.
FAU - Takikawa, Yasuhiro
AU  - Takikawa Y
AD  - Iwate Medical University, Iwate, Japan.
FAU - Kanda, Tatsuo
AU  - Kanda T
AD  - Chiba University, Chiba, Japan.
FAU - Sakamoto, Minoru
AU  - Sakamoto M
AD  - University of Yamanashi, Yamanashi, Japan.
FAU - Tamori, Akihiro
AU  - Tamori A
AD  - Osaka City University, Osaka, Japan.
FAU - Mita, Eiji
AU  - Mita E
AD  - National Hospital Organization Osaka National Hospital, Osaka, Japan.
FAU - Chayama, Kazuaki
AU  - Chayama K
AD  - Hiroshima University, Hiroshima, Japan.
FAU - Zhang, Gulan
AU  - Zhang G
AD  - Gilead Sciences, Inc, Foster City, CA, USA.
FAU - De-Oertel, Shampa
AU  - De-Oertel S
AD  - Gilead Sciences, Inc, Foster City, CA, USA.
FAU - Dvory-Sobol, Hadas
AU  - Dvory-Sobol H
AD  - Gilead Sciences, Inc, Foster City, CA, USA.
FAU - Matsuda, Takuma
AU  - Matsuda T
AD  - Gilead Sciences K.K, Tokyo, Japan.
FAU - Stamm, Luisa M
AU  - Stamm LM
AD  - Gilead Sciences, Inc, Foster City, CA, USA.
FAU - Brainard, Diana M
AU  - Brainard DM
AD  - Gilead Sciences, Inc, Foster City, CA, USA.
FAU - Tanaka, Yasuhito
AU  - Tanaka Y
AD  - Nagoya City University, Nagoya, Aichi, Japan.
FAU - Kurosaki, Masayuki
AU  - Kurosaki M
AD  - Musashino Red Cross Hospital, Tokyo, Japan.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20180910
PL  - Japan
TA  - J Gastroenterol
JT  - Journal of gastroenterology
JID - 9430794
RN  - 0 (Antiviral Agents)
RN  - 0 (Carbamates)
RN  - 0 (Drug Combinations)
RN  - 0 (Heterocyclic Compounds, 4 or More Rings)
RN  - 0 (sofosbuvir-velpatasvir drug combination)
RN  - 49717AWG6K (Ribavirin)
RN  - WJ6CA3ZU8B (Sofosbuvir)
SB  - IM
CIN - J Gastroenterol. 2019 Mar;54(3):299-300. PMID: 30599052
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antiviral Agents/administration & dosage/adverse effects
MH  - Carbamates/*administration & dosage/adverse effects
MH  - Drug Combinations
MH  - Female
MH  - Genotype
MH  - Hepacivirus/genetics
MH  - Hepatitis C/*drug therapy
MH  - Heterocyclic Compounds, 4 or More Rings/*administration & dosage/adverse effects
MH  - Humans
MH  - Japan
MH  - Liver Cirrhosis/*drug therapy/virology
MH  - Male
MH  - Middle Aged
MH  - Ribavirin/*administration & dosage/adverse effects
MH  - Sofosbuvir/*administration & dosage/adverse effects
MH  - Sustained Virologic Response
MH  - Treatment Outcome
PMC - PMC6314981
OTO - NOTNLM
OT  - Advanced liver disease
OT  - Decompensated cirrhosis
OT  - Direct-acting antivirals
OT  - Sofosbuvir
OT  - Velpatasvir
COIS- Tetsuo Takehara has received honoraria and commercial research funding from 
      Gilead. Naoya Sakamoto has received honoraria from Bristol-Myers Squibb, Merck 
      Sharp & Dohme, and Gilead, and has received commercial research funding from 
      Gilead, AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Otsuka, and Shionogi. 
      Shuhei Nishiguchi has received honoraria from Gilead, and has received commercial 
      research funding from Gilead, Toray and Merck Sharp & Dohme. Yoshiyuki Ueno 
      received commercial research funding from Gilead, Bristol-Myers Squibb, AbbVie, 
      and Merck Sharp & Dohme. Hiroshi Yatshuhashi has received commercial research 
      funding from Chugai. Tatsuo Kanda has received commercial research funding from 
      AbbVie, Merck Sharp & Dohme, Chugai, and Sysmex. Minoru Sakamoto has received 
      honoraria from Bristol-Myers Squibb, Merck Sharp & Dohme, and Gilead, and has 
      received commercial research funding from Gilead, AbbVie, Bristol-Myers Squibb, 
      Merck Sharp & Dohme, Otsuka, and Shionogi. Akihiro Tamori has received honoraria 
      from Gilead. Kazuaki Chayama has received honoraria from AbbVie, Merck Sharp & 
      Dohme, Bristol-Myers Squibb, and Gilead. Gulan Zhang, Shampa De-Oertel, Hadas 
      Dvory-Sobol, Takuma Matsuda, Luisa M. Stamm, and Diana M. Brainard are employees 
      of and hold stock in Gilead Sciences. Yasuhito Tanaka has received honoraria from 
      Bristol-Myers Squibb and Gilead Sciences, and has received commercial research 
      funding from Chugai, AbbVie, Bristol-Myers Squibb, Janssen, and Gilead. Masayuki 
      Kurosaki has served in an advisory role to AbbVie, Gilead, GlaxoSmithKline, and 
      Otsuka, and has received honoraria from AbbVie, Bristol-Myers Squibb, Chugai, 
      Daiichi Sankyo, Gilead, GlaxoSmithKline, Janssen, Merck Sharp & Dohme, Otsuka, 
      and Toray. Fusao Ikeda, Tomohide Tatsumi, Yasuhiro Takikawa, and Eiji Mita, 
      declare no conflicts of interest.
EDAT- 2018/09/12 06:00
MHDA- 2019/12/18 06:00
PMCR- 2018/09/10
CRDT- 2018/09/12 06:00
PHST- 2018/06/29 00:00 [received]
PHST- 2018/08/22 00:00 [accepted]
PHST- 2018/09/12 06:00 [pubmed]
PHST- 2019/12/18 06:00 [medline]
PHST- 2018/09/12 06:00 [entrez]
PHST- 2018/09/10 00:00 [pmc-release]
AID - 10.1007/s00535-018-1503-x [pii]
AID - 1503 [pii]
AID - 10.1007/s00535-018-1503-x [doi]
PST - ppublish
SO  - J Gastroenterol. 2019 Jan;54(1):87-95. doi: 10.1007/s00535-018-1503-x. Epub 2018 
      Sep 10.