Daclatasvir plus sofosbuvir, with or without ribavirin, achieved high sustained virological response rates in patients with HCV infection and advanced liver disease in a real-world cohort.
We assessed the effectiveness and safety of daclatasvir (DCV) plus sofosbuvir (SOF), with or without ribavirin (RBV), in a large real-world cohort, including patients with advanced liver disease.



Adults with chronic HCV infection at high risk of decompensation or death within 12 months and with no available treatment options were treated in a European compassionate use programme. The recommended regimen was DCV 60 mg plus SOF 400 mg for 24 weeks; RBV addition or shorter duration was allowed at physicians' discretion. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12).



Of the 485 evaluable patients, 359 received DCV+SOF and 126 DCV+SOF+RBV. Most patients were men (66%), white (93%) and treatment-experienced (70%). The most frequent HCV genotypes were 1b (36%), 1a (33%) and 3 (21%), and 80% of patients had cirrhosis (42% Child-Pugh B/C; 46% Model for End-Stage Liver Disease score >10). SVR12 (modified intention-to-treat) was achieved by 91% of patients (419/460); 1 patient had virological breakthrough and 13 patients relapsed. Virological failure was not associated with treatment group (adjusted risk difference DCV+SOF minus DCV+SOF+RBV: 1.06%; 95% CI -2.22% to 4.35%). High SVR12 was observed regardless of HCV genotype or cirrhosis, liver transplant or HIV/HCV coinfection status. Twenty eight patients discontinued treatment due to adverse events (n=18) or death (n=10) and 18 died during follow-up. Deaths and most safety events were associated with advanced liver disease and not considered treatment related.



DCV+SOF with or without RBV achieved high SVR12 and was well tolerated in a diverse cohort of patients with severe liver disease.



NCT02097966.
Universitätsklinikum der Johann Wolfgang Goethe Universität, Frankfurt am Main, Germany.
Tania M
TM
Welzel
IFI Institut für Interdisziplinäre Medizin, Hamburg, Germany.
Jörg
J
Petersen
Universitätsklinikum Essen (AöR), Essen, Germany.
Kerstin
K
Herzer
Department of Internal Medicine III, Medizinische Universität Wien, Vienna, Austria.
Peter
P
Ferenci
Wilhelminenspital, Vienna, Austria.
Michael
M
Gschwantler
Medizinische Hochschule Hannover, Hannover, Germany.
Heiner
H
Wedemeyer
Universitätsklinikum Leipzig, Leipzig, Germany.
Thomas
T
Berg
Universitätsklinikum Bonn, Bonn, Germany.
Ulrich
U
Spengler
Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Ola
O
Weiland
Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Marc
M
van der Valk
Universitätsklinikum Bonn, Bonn, Germany.
Jürgen
J
Rockstroh
Department of Internal Medicine III, Medizinische Universität Wien, Vienna, Austria.|Klinikum Klagenfurt am Wörthersee, Klagenfurt, Austria.
Markus
M
Peck-Radosavljevic
Bristol-Myers Squibb, Princeton, New Jersey, USA.
Yue
Y
Zhao
Bristol-Myers Squibb, Princeton, New Jersey, USA.
Maria Jesus
MJ
Jimenez-Exposito
Universitätsklinikum der Johann Wolfgang Goethe Universität, Frankfurt am Main, Germany.
Stefan
S
Zeuzem
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects; D002219:Carbamates; D015331:Cohort Studies; D057176:Compassionate Use Trials; D016903:Drug Monitoring / Q000379:methods; D004359:Drug Therapy, Combination / Q000379:methods; D005060:Europe; D005260:Female; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects; D017093:Liver Failure / Q000150:complications / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects; D012720:Severity of Illness Index; D000069474:Sofosbuvir / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives
D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D011759:Pyrrolidines; D012254:Ribavirin; D014633:Valine; C549273:daclatasvir; D000069474:Sofosbuvir
ANTIVIRAL THERAPY; CHRONIC VIRAL HEPATITIS; CIRRHOSIS; HEPATITIS C