title: Sofosbuvir and Velpatasvir for HCV in Patients with Decompensated Cirrhosis.
abstract: BACKGROUND
  As the population that is infected with the hepatitis C virus (HCV) ages, the number of patients with decompensated cirrhosis is expected to increase.
  
  
  METHODS
  We conducted a phase 3, open-label study involving both previously treated and previously untreated patients infected with HCV genotypes 1 through 6 who had decompensated cirrhosis (classified as Child-Pugh-Turcotte class B). Patients were randomly assigned in a 1:1:1 ratio to receive the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir once daily for 12 weeks, sofosbuvir-velpatasvir plus ribavirin for 12 weeks, or sofosbuvir-velpatasvir for 24 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy.
  
  
  RESULTS
  Of the 267 patients who received treatment, 78% had HCV genotype 1, 4% genotype 2, 15% genotype 3, 3% genotype 4, and less than 1% genotype 6; no patients had genotype 5. Overall rates of sustained virologic response were 83% (95% confidence interval [CI], 74 to 90) among patients who received 12 weeks of sofosbuvir-velpatasvir, 94% (95% CI, 87 to 98) among those who received 12 weeks of sofosbuvir-velpatasvir plus ribavirin, and 86% (95% CI, 77 to 92) among those who received 24 weeks of sofosbuvir-velpatasvir. Post hoc analysis did not detect any significant differences in rates of sustained virologic response among the three study groups. Serious adverse events occurred in 19% of patients who received 12 weeks of sofosbuvir-velpatasvir, 16% of those who received 12 weeks of sofosbuvir-velpatasvir plus ribavirin, and 18% of those who received 24 weeks of sofosbuvir-velpatasvir. The most common adverse events were fatigue (29%), nausea (23%), and headache (22%) in all patients and anemia (31%) in the patients receiving ribavirin.
  
  
  CONCLUSIONS
  Treatment with sofosbuvir-velpatasvir with or without ribavirin for 12 weeks and with sofosbuvir-velpatasvir for 24 weeks resulted in high rates of sustained virologic response in patients with HCV infection and decompensated cirrhosis. (Funded by Gilead Sciences; ASTRAL-4 ClinicalTrials.gov number, NCT02201901.).
authors.affiliation: From the Beth Israel Deaconess Medical Center, Boston (M.P.C.); Baylor University Medical Center, Dallas (J.G.O.), and Texas Liver Institute, University of Texas Health Science Center, San Antonio (E.L.) - both in Texas; Ochsner Medical Center, New Orleans (N.B.); Duke University, Durham (A.J.M.), and School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill (M.F.) - both in North Carolina; Washington University School of Medicine, St. Louis (K.M.K.); Thomas Jefferson University (J.M.F.) and University of Pennsylvania School of Medicine (K.R.R.) - both in Philadelphia; Northwestern University, Chicago (S.L.F.); Mount Sinai Hospital (T.S.), New York University School of Medicine (L.T.), and Weill Cornell Medical College (R.S.B.) - all in New York; University of Michigan, Ann Arbor (R.F.); University of Miami, Miami (E.S.); Gilead Sciences, Foster City, CA (B.D., D.A., J.M., A.O., D.M.B., J.G.M.); and Intermountain Medical Center, Salt Lake City (M.C.).
authors.forename: Michael P
authors.initials: MP
authors.lastname: Curry
authors.forename: Jacqueline G
authors.initials: JG
authors.lastname: O'Leary
authors.forename: Natalie
authors.initials: N
authors.lastname: Bzowej
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Muir
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Korenblat
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Fenkel
authors.forename: K Rajender
authors.initials: KR
authors.lastname: Reddy
authors.forename: Eric
authors.initials: E
authors.lastname: Lawitz
authors.forename: Steven L
authors.initials: SL
authors.lastname: Flamm
authors.forename: Thomas
authors.initials: T
authors.lastname: Schiano
authors.forename: Lewis
authors.initials: L
authors.lastname: Teperman
authors.forename: Robert
authors.initials: R
authors.lastname: Fontana
authors.forename: Eugene
authors.initials: E
authors.lastname: Schiff
authors.forename: Michael
authors.initials: M
authors.lastname: Fried
authors.forename: Brian
authors.initials: B
authors.lastname: Doehle
authors.forename: Di
authors.initials: D
authors.lastname: An
authors.forename: John
authors.initials: J
authors.lastname: McNally
authors.forename: Anu
authors.initials: A
authors.lastname: Osinusi
authors.forename: Diana M
authors.initials: DM
authors.lastname: Brainard
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.forename: Robert S
authors.initials: RS
authors.lastname: Brown
authors.forename: Michael
authors.initials: M
authors.lastname: Charlton
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002219:Carbamates / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004338:Drug Combinations; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006576:Heterocyclic Compounds, 4 or More Rings / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000209:etiology; D008297:Male; D008875:Middle Aged; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use; D000069474:Sofosbuvir / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D012324:RNA-Dependent RNA Polymerase; D001562:Benzimidazoles; D001578:Benzopyrans
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D004338:Drug Combinations; D006576:Heterocyclic Compounds, 4 or More Rings; D012254:Ribavirin; D000069474:Sofosbuvir; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C000604171:velpatasvir; D001562:Benzimidazoles; D001578:Benzopyrans