title: Daclatasvir plus asunaprevir for HCV genotype 1b infection in patients with or without compensated cirrhosis: a pooled analysis.
abstract: We compared outcomes by cirrhosis status across studies of the all-oral combination of daclatasvir (DCV) plus asunaprevir (ASV).
  
  
  
  Outcomes from global and Japanese phase 2 and 3 clinical studies of DCV+ASV in patients with genotype (GT) 1b infection were assessed by cirrhosis status. Sustained virological response (SVR) was assessed in individual phase 3 studies; a pooled analysis was carried out for safety outcomes.
  
  
  
  In the Japanese phase 3 study, SVR12 was achieved by 91% of patients with cirrhosis (n = 22) and 84% of patients without cirrhosis (n = 200); in the global phase 3 study, SVR12 was achieved by 84% of patients with cirrhosis (n = 206) and by 85% of patients without cirrhosis (n = 437). The frequency of serious adverse events, adverse events leading to treatment discontinuation and treatment-emergent grade 3/4 laboratory abnormalities was low (<10%) and similar among patients with (n = 229) or without (n = 689) compensated cirrhosis receiving DCV+ASV. Grade 3/4 reductions in platelets and neutrophils were more common among patients with cirrhosis (1.3 and 2.2%, respectively) compared with those without cirrhosis (both 0.6%). Grade 3/4 liver function test abnormalities were less common among patients with cirrhosis (1.8%) compared with those without cirrhosis (3.5-4.7%). Alanine aminotransferase elevations were not associated with hepatic decompensation.
  
  
  
  The safety and efficacy of DCV+ASV were similar in patients with or without compensated cirrhosis. This all-oral, interferon- and ribavirin-free combination is an effective and well-tolerated treatment option for patients with HCV GT1b infection and cirrhosis. Trial registrations numbers: Clinicaltrials.gov identifiers: NCT01012895; NCT01051414; NCT01581203; NCT01497834.
authors.affiliation: Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Jia-Horng
authors.initials: JH
authors.lastname: Kao
authors.affiliation: Center for Liver Diseases, University of Chicago Medical Center, Chicago, IL, USA.
authors.forename: Donald M
authors.initials: DM
authors.lastname: Jensen
authors.affiliation: Hannover Medical School, Hannover, Germany.|German Center for Infection Research, Hannover-Braunschweig, Germany.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.affiliation: Department of Medicine at Mount Sinai Beth Israel Medical Center, New York, NY, USA.
authors.forename: Ira
authors.initials: I
authors.lastname: Jacobson
authors.affiliation: Toranomon Hospital, Tokyo, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
authors.affiliation: Sapporo-Kosei General Hospital, Sapporo, Japan.
authors.forename: Joji
authors.initials: J
authors.lastname: Toyota
authors.affiliation: College of Medicine, Pusan National University and Medical Research Institute, Pusan National University Hospital, Busan, South Korea.
authors.forename: Jeong
authors.initials: J
authors.lastname: Heo
authors.affiliation: Veterans Affairs Medical Center, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Boris
authors.initials: B
authors.lastname: Yoffe
authors.affiliation: Monash Health and Monash University, Melbourne, Victoria, Australia.
authors.forename: William
authors.initials: W
authors.lastname: Sievert
authors.affiliation: Hospital Provincial del Centenario, Servicio de Gastroenterología y Hepatología, Universidad Nacional de Rosario, Rosario, Argentina.
authors.forename: Fernando
authors.initials: F
authors.lastname: Bessone
authors.affiliation: School of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Cheng-Yuan
authors.initials: CY
authors.lastname: Peng
authors.affiliation: Alfred Hospital and Monash University, Melbourne, Victoria, Australia.
authors.forename: Stuart K
authors.initials: SK
authors.lastname: Roberts
authors.affiliation: Inje University Busan Paik Hospital, Busan, South Korea.
authors.forename: Youn-Jae
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Bristol-Myers Squibb Research and Development, Princeton, NJ, USA.
authors.forename: Rafia
authors.initials: R
authors.lastname: Bhore
authors.affiliation: Bristol-Myers Squibb Research and Development, Princeton, NJ, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Mendez
authors.affiliation: Bristol-Myers Squibb Research and Development, Princeton, NJ, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Hughes
authors.affiliation: Bristol-Myers Squibb Research and Development, Princeton, NJ, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Noviello
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002219:Carbamates; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D007391:International Cooperation; D007546:Isoquinolines / Q000008:administration & dosage* / Q000009:adverse effects; D008099:Liver / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects; D000072230:Sustained Virologic Response; D014633:Valine / Q000031:analogs & derivatives
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D007546:Isoquinolines; D011759:Pyrrolidines; D013449:Sulfonamides; D000410:Alanine Transaminase; D014633:Valine; C549273:daclatasvir; C571889:asunaprevir
keywords: cirrhosis; direct acting antiviral; hepatitis C; safety