title: Real-world efficacy and safety of daclatasvir and asunaprevir therapy for hepatitis C virus-infected cirrhosis patients.
abstract: OBJECTIVE
  Daclatasvir and asunaprevir combination therapy has shown a high virological response for chronic genotype 1 hepatitis C virus (HCV) infected-patients. However, the real-world efficacy and safety of the therapy for patients with cirrhosis are unknown.
  
  
  METHODS
  A total of 252 patients with genotype 1 HCV infection (158 with chronic hepatitis and 94 with compensated liver cirrhosis) were treated with 24 weeks of daclatasvir and asunaprevir combination therapy. Plasma concentrations of daclatasvir and asunaprevir at day 5 of treatment, end-of-treatment response, sustained virological response (SVR), and the frequencies of adverse events were analyzed.
  
  
  RESULTS
  Plasma asunaprevir concentration was significantly higher, and daclatasvir concentration tended to be higher, in cirrhosis patients compared with chronic hepatitis patients. End-of-treatment response was achieved in 95.6% and 94.7% of chronic hepatitis and cirrhosis patients, respectively, and SVR was achieved in 94.3% and 92.6%. Although pre-treatment NS5A drug resistant-associated variants were detected, a high SVR rate was achieved when the population frequency of the variant was low. The frequencies of treatment-related adverse events in cirrhosis patients were similar to those in chronic hepatitis patients. Treatment discontinuation due to adverse events occurred in three and two patients in chronic hepatitis and cirrhosis groups, respectively; however, four out of five patients with treatment discontinuation nonetheless achieved SVR.
  
  
  CONCLUSIONS
  Patients with compensated liver cirrhosis have similar virological response and tolerance for daclatasvir plus asunaprevir therapy to patients with chronic hepatitis. This combination therapy might offer a safe and effective treatment for chronic HCV infected-patients with compensated cirrhosis.
authors: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.
authors: Kei
authors: K
authors: Morio
authors: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.
authors: Michio
authors: M
authors: Imamura
authors: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.
authors: Yoshiiku
authors: Y
authors: Kawakami
authors: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.
authors: Reona
authors: R
authors: Morio
authors: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.
authors: Tomoki
authors: T
authors: Kobayashi
authors: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.
authors: Satoe
authors: S
authors: Yokoyama
authors: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.
authors: Yuko
authors: Y
authors: Nagaoki
authors: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.
authors: Tomokazu
authors: T
authors: Kawaoka
authors: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.
authors: Masataka
authors: M
authors: Tsuge
authors: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.
authors: Akira
authors: A
authors: Hiramatsu
authors: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.
authors: Grace Naswa
authors: GN
authors: Makokha
authors: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.
authors: C Nelson
authors: CN
authors: Hayes
authors: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.
authors: Hiroshi
authors: H
authors: Aikata
authors: Laboratory for Digestive Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Hiroshima, Japan.
authors: Daiki
authors: D
authors: Miki
authors: Laboratory for Digestive Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Hiroshima, Japan.
authors: Hidenori
authors: H
authors: Ochi
authors: Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Hiroshima, Japan.
authors: Yoji
authors: Y
authors: Honda
authors: Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Hiroshima, Japan.
authors: Nami
authors: N
authors: Mori
authors: Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Hiroshima, Japan.
authors: Shintaro
authors: S
authors: Takaki
authors: Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Hiroshima, Japan.
authors: Keiji
authors: K
authors: Tsuji
authors: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.|Laboratory for Digestive Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Hiroshima, Japan.
authors: Kazuaki
authors: K
authors: Chayama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002219:Carbamates; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D007546:Isoquinolines / Q000008:administration & dosage* / Q000009:adverse effects; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D007546:Isoquinolines; D011759:Pyrrolidines; D013449:Sulfonamides; D014633:Valine; C549273:daclatasvir; C571889:asunaprevir
keywords: asunaprevir; chronic hepatitis C; cirrhosis; daclatasvir