title: Ombitasvir/paritaprevir/r, dasabuvir and ribavirin for cirrhotic HCV patients with thrombocytopaenia and hypoalbuminaemia.
abstract: OBJECTIVE
  Thrombocytopaenia and hypoalbuminaemia are surrogate markers for portal hypertension and hepatic synthetic dysfunction respectively. Patients infected with hepatitis C virus (HCV) with these surrogates have reduced likelihood of sustained virologic response and increased risk for hepatic decompensation or death when treated with peginterferon/ribavirin plus either telaprevir or boceprevir.
  
  
  METHODS
  We conducted a post-hoc analysis of the TURQUOISE-II clinical trial in patients with cirrhosis to examine the impact of these surrogates on efficacy and safety of ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin.
  
  
  RESULTS
  Of 380 genotype 1-infected patients in TURQUOISE-II, 104 had either a platelet count <100 × 10(9)/L or albumin <3.5 g/dl. Sustained virologic response rates were 89 and 97% in patients with thrombocytopaenia, and 84 and 89% in patients with hypoalbuminaemia after 12 and 24 weeks of ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin respectively. These rates were similar to those observed in the overall study population (92 and 97% for 12 and 24 weeks). HCV genotype 1a-infected patients with thrombocytopaenia or hypoalbuminaemia had higher response rates when treated for 24 weeks, whereas only 1 of 35 genotype 1b patients did not achieve a sustained virologic response. Adverse event rates and discontinuations because of adverse events were low.
  
  
  CONCLUSIONS
  The findings of these analyses support the use of ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin in these subpopulations with cirrhosis. Genotype 1a-infected patients with indicators of portal hypertension may benefit from a 24-week treatment duration.
authors.affiliation: Liver Unit, Hospital Clinic, CIBERehd, IDIBAPS, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Forns
authors.affiliation: The Texas Liver Institute/University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: Fred
authors.initials: F
authors.lastname: Poordad
authors.affiliation: AbbVie Inc., North Chicago, IL, USA.
authors.forename: Marcos
authors.initials: M
authors.lastname: Pedrosa
authors.affiliation: La Fe University Hospital and CIBERehd, Valencia, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: Berenguer
authors.affiliation: Hannover Medical School, Hannover, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
authors.affiliation: Medical University of Vienna, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
authors.affiliation: Liver Institute of Virginia, Bon Secours Health System, Newport News, VA, USA.|Liver Institute of Virginia, Bon Secours Health System, Richmond, VA, USA.
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Shiffman
authors.affiliation: University of North Carolina at Chapel Hill, UNC Liver Center, Chapel Hill, NC, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Fried
authors.affiliation: AbbVie Inc., North Chicago, IL, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Lovell
authors.affiliation: AbbVie Inc., North Chicago, IL, USA.
authors.forename: Roger
authors.initials: R
authors.lastname: Trinh
authors.affiliation: AbbVie Inc., North Chicago, IL, USA.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Lopez-Talavera
authors.affiliation: University of Colorado Denver School of Medicine, Aurora, CO, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Everson
mesh_terms: D015081:2-Naphthylamine; D000293:Adolescent; D000328:Adult; D000368:Aged; D000813:Anilides / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use*; D002219:Carbamates / Q000627:therapeutic use*; D003521:Cyclopropanes; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D006975:Hypertension, Portal / Q000503:physiopathology; D034141:Hypoalbuminemia / Q000188:drug therapy; D047029:Lactams, Macrocyclic; D008103:Liver Cirrhosis / Q000821:virology; D047028:Macrocyclic Compounds / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011392:Proline / Q000031:analogs & derivatives; D012254:Ribavirin / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D013921:Thrombocytopenia / Q000188:drug therapy; D016896:Treatment Outcome; D014498:Uracil / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014633:Valine; D055815:Young Adult
chemical_list: D000813:Anilides; D000998:Antiviral Agents; D002219:Carbamates; D003521:Cyclopropanes; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds; D013449:Sulfonamides; C586094:ombitasvir; D012254:Ribavirin; D014498:Uracil; D011392:Proline; D015081:2-Naphthylamine; C588260:dasabuvir; D014633:Valine; C585405:paritaprevir
keywords: TURQUOISE-II; direct-acting antiviral agents; hepatitis C virus; portal hypertension