title: Addition of ribavirin to daclatasvir plus asunaprevir for chronic hepatitis C 1b patients with baseline NS5A resistance-associated variants improved response.
abstract: OBJECTIVE
  Daclatasvir is a nonstructural protein 5A inhibitor with potent activity against hepatitis C virus genotypes 1-6 in vitro, and asunaprevir is a nonstructural protein 3 protease inhibitor with activity against genotypes 1, 4, 5, and 6. Despite a 90% sustained virologic response (SVR) rate, the SVR rate in patients with baseline NS5A-L31/Y93H polymorphisms decreased to around 40%. Therefore, an alternative regimen under the consideration of cost-effectiveness would be important. Whether the addition of ribavirin could improve the SVR rate among this group of patients remains unknown and hence our case series was reported.
  
  
  METHODS
  For six adult chronic hepatitis C 1b patients with a pre-existing NS5A-Y93H (>20%) polymorphism, we added ribavirin (800 mg/d) to daclatasvir/asunaprevir for 24 weeks and followed through 12-weeks post-treatment. Four of these patients received interferon/ribavirin treatment before but relapsed, while the other two were naïve cases. Two of them had liver cirrhosis and one had hepatocellular carcinoma postcurative therapy. The primary efficacy end-point was undetectable hepatitis C virus RNA (hepatitis C virus RNA level of<25 IU/mL) at 12 weeks after the end of the treatment (SVR12).
  
  
  RESULTS
  In total, five cases reached SVR12 eventually (SVR rate: 83%; 95% confidence interval: 18.6-99.1%). However, the viral load of one remaining patient rebounded from the 24thweek of treatment. No patients developed significant adverse effects during and after the treatment.
  
  
  CONCLUSIONS
  In genotype 1b chronic hepatitis C patients with NS5A-Y93H polymorphism, the addition of ribavirin to daclatasvir/asunaprevir may increase the SVR12 rate with minimal side effects, and thus deserves more comprehensive trials in resource-limited areas.
authors.affiliation: Department of Traumatology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Hong
authors.affiliation: Department of Internal Medicine and Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Liu
authors.affiliation: Department of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Shiou-Hwei
authors.initials: SH
authors.lastname: Yeh
authors.affiliation: Department of Traumatology, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: peijerchen@ntu.edu.tw.
authors.forename: Pei-Jer
authors.initials: PJ
authors.lastname: Chen
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D002219:Carbamates; D024882:Drug Resistance, Viral / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D007546:Isoquinolines / Q000627:therapeutic use; D008103:Liver Cirrhosis; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011759:Pyrrolidines; D012254:Ribavirin / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use; D013624:Taiwan; D014633:Valine / Q000031:analogs & derivatives; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D007546:Isoquinolines; D011759:Pyrrolidines; D012254:Ribavirin; D013449:Sulfonamides; D014633:Valine; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C549273:daclatasvir; C571889:asunaprevir
keywords: direct-acting antivirals; hepatitis C; resistance-associated variant