PMID- 26033798
OWN - NLM
STAT- MEDLINE
DCOM- 20151125
LR  - 20220331
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Print)
IS  - 0270-9139 (Linking)
VI  - 62
IP  - 3
DP  - 2015 Sep
TI  - Safety and Efficacy of Simeprevir/Sofosbuvir in Hepatitis C-Infected Patients 
      With Compensated and Decompensated Cirrhosis.
PG  - 715-25
LID - 10.1002/hep.27922 [doi]
AB  - Risks and benefits of simeprevir plus sofosbuvir (SIM+SOF) in patients with 
      advanced cirrhosis are unknown. We assessed the safety and sustained virological 
      responses (SVR) of SIM+SOF with and without ribavirin (RBV) in patients with 
      Child-Pugh (CP)-B/C versus CP-A cirrhosis and compared to matched untreated 
      controls. This study was of a multicenter cohort of adults with hepatitis C virus 
      genotype 1 and cirrhosis treated with SIM+SOF with/without RBV for 12 weeks. 
      Controls were matched on treatment center, age, CP class, and Model for End-Stage 
      Liver Disease (MELD) score. Of 160 patients treated with SIM+SOF with/without 
      RBV, 35% had CP-B/C and 64% had CP-A, with median baseline MELD 9 (interquartile 
      range, 8-11). Sustained virological response at week 12 (SVR12) was achieved by 
      73% of CP-B/C versus 91% of CP-A (P < 0.01). CP-B/C versus CP-A had more early 
      treatment discontinuations (11% vs. 1%), adverse events (AEs) requiring 
      hospitalization (22% vs. 2%), infections requiring antibiotics (20% vs. 1%), and 
      hepatic decompensating events (20% vs. 3%; all P < 0.01). There were 2 deaths: 1 
      CP-B/C (liver related) and 1 CP-A (not liver related). In multivariate analysis, 
      CP-B/C independently predicted lack of SVR12 (odds ratio, 0.27; 95% confidence 
      interval: 0.08-0.92). In comparing SIM+SOF-treated patients versus matched 
      untreated controls, AEs requiring hospitalization (9% vs. 13%; P = 0.55), 
      infections (8% vs. 6%; P = 0.47), and events of decompensation (9% vs. 10%; 
      P = 0.78) occurred at similar frequency. CONCLUSIONS: SIM+SOF with/without RBV 
      has lower efficacy and higher rates of AEs in patients with CP-B/C cirrhosis, 
      compared to CP-A. Frequency of adverse safety outcomes were similar to matched 
      untreated controls, suggesting that safety events reflect the natural history of 
      cirrhosis and are not related to treatment.
CI  - (c) 2015 by the American Association for the Study of Liver Diseases.
FAU - Saxena, Varun
AU  - Saxena V
AD  - University of California San Francisco, San Francisco, CA.
FAU - Nyberg, Lisa
AU  - Nyberg L
AD  - Kaiser Permanente Southern California, San Diego, CA.
FAU - Pauly, Marypat
AU  - Pauly M
AD  - Kaiser Permanente Northern California, Oakland, CA.
FAU - Dasgupta, Aditi
AU  - Dasgupta A
AD  - University of California San Francisco, San Francisco, CA.
FAU - Nyberg, Anders
AU  - Nyberg A
AD  - Kaiser Permanente Southern California, San Diego, CA.
FAU - Piasecki, Barbara
AU  - Piasecki B
AD  - Kaiser Permanente Colorado, Denver, CO.
FAU - Winston, Bradley
AU  - Winston B
AD  - Kaiser Permanente Mid-Atlantic, Rockville, MD.
FAU - Redd, Jacquelyn
AU  - Redd J
AD  - Kaiser Permanente Mid-Atlantic, Rockville, MD.
FAU - Ready, Joanna
AU  - Ready J
AD  - Kaiser Permanente Northern California, Oakland, CA.
FAU - Terrault, Norah A
AU  - Terrault NA
AD  - University of California San Francisco, San Francisco, CA.
LA  - eng
GR  - P30 DK026743/DK/NIDDK NIH HHS/United States
GR  - T32 DK060414/DK/NIDDK NIH HHS/United States
GR  - P30 DK 026743/DK/NIDDK NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
DEP - 20150730
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (Antiviral Agents)
RN  - 49717AWG6K (Ribavirin)
RN  - 9WS5RD66HZ (Simeprevir)
RN  - WJ6CA3ZU8B (Sofosbuvir)
SB  - IM
MH  - Aged
MH  - Analysis of Variance
MH  - Antiviral Agents/administration & dosage
MH  - Case-Control Studies
MH  - Drug Therapy, Combination
MH  - Female
MH  - Follow-Up Studies
MH  - Hepacivirus/drug effects
MH  - Hepatitis C/*drug therapy/pathology
MH  - Humans
MH  - Liver Cirrhosis/drug therapy/*pathology/physiopathology
MH  - Logistic Models
MH  - Male
MH  - Middle Aged
MH  - Multivariate Analysis
MH  - Patient Safety
MH  - Reference Values
MH  - Retrospective Studies
MH  - Ribavirin/*administration & dosage/adverse effects
MH  - Risk Assessment
MH  - Severity of Illness Index
MH  - Simeprevir/*administration & dosage/adverse effects
MH  - Sofosbuvir/*administration & dosage/adverse effects
MH  - Treatment Outcome
PMC - PMC4549204
MID - NIHMS698224
EDAT- 2015/06/03 06:00
MHDA- 2015/12/15 06:00
PMCR- 2016/09/01
CRDT- 2015/06/03 06:00
PHST- 2015/03/28 00:00 [received]
PHST- 2015/05/29 00:00 [accepted]
PHST- 2015/06/03 06:00 [entrez]
PHST- 2015/06/03 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
PHST- 2016/09/01 00:00 [pmc-release]
AID - 10.1002/hep.27922 [doi]
PST - ppublish
SO  - Hepatology. 2015 Sep;62(3):715-25. doi: 10.1002/hep.27922. Epub 2015 Jul 30.