title: Evaluation of proton pump inhibitor use on treatment outcomes with ledipasvir and sofosbuvir in a real-world cohort study.
abstract: Many patients with chronic hepatitis C virus (HCV) are on prolonged proton-pump inhibitor (PPI) therapy and wish to remain on PPI therapy once treatment for HCV starts. A preliminary report recently suggested decrease rates of sustained virological response (SVR) for patients taking concomitant PPI and ledipasvir/sofosbuvir (LDV/SOF). We sought to determine the effect of PPI use on the rate of SVR in a real-world cohort of 1,979 patients with chronic HCV treated with LDV/SOF. We collected clinical data and pharmacy dispensing records on patients taking 8, 12, or 24 weeks of LDV/SOF ± ribavirin (RBV). The primary outcome was sustained virological response at 12 weeks after treatment completion (SVR12) in a per-protocol analysis in order to determine the effect of PPI use adjusted for confounders. Statistical adjustment was performed in propensity-matched analysis. Among treatment completers, SVR12 was achieved in 441 (97.1%) of PPI recipients compared with 1,497 (98.2%) in PPI nonrecipients (P = 0.19). Neither low- nor high-dose PPI was associated with decreased SVR, although patients taking twice-daily PPI achieved a lower SVR12 rate (91.2%; 95% confidence interval [CI], 77.0-97.0; P = 0.046). After propensity matching for PPI use, there were no significant associations between SVR12 and any dose or frequency of PPI use. However, in a sensitivity analysis focusing on patients with cirrhosis, twice-daily PPI use was associated with lower odds ratio for SVR12 (0.11; 95% CI, 0.02-0.59).
  
  
  
  These data from a cohort of real-world patients receiving hepatitis C antibody therapy with LDF/SOF ± RBV support the prescription labeling suggesting that patients take no more than low-dose (20-mg omeprazole equivalents) PPI daily. (Hepatology 2016;64:1893-1899).
authors.affiliation: Division of Gastroenterology/Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Elliot B
authors.initials: EB
authors.lastname: Tapper
authors.affiliation: Division of Gastroenterology/ Hepatology, Saint Louis University School of Medicine, Saint Louis, MO.
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Bacon
authors.affiliation: Division of Gastroenterology/Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Curry
authors.affiliation: Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, NY.
authors.forename: Douglas T
authors.initials: DT
authors.lastname: Dieterich
authors.affiliation: Division of Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Flamm
authors.affiliation: Trio Health Analytics, La Jolla, CA.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Guest
authors.affiliation: Liver Care Network, Swedish Medical Center, Seattle, WA.
authors.forename: Kris V
authors.initials: KV
authors.lastname: Kowdley
authors.affiliation: Trio Health Analytics, La Jolla, CA.
authors.forename: Yoori
authors.initials: Y
authors.lastname: Lee
authors.affiliation: The Liver Center, Queen's Medical Center, Honolulu, HI.
authors.forename: Naoky C
authors.initials: NC
authors.lastname: Tsai
authors.affiliation: Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, VA.
authors.forename: Zobair M
authors.initials: ZM
authors.lastname: Younossi
authors.affiliation: Division of Gastroenterology/Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Nezam H
authors.initials: NH
authors.lastname: Afdhal
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D015331:Cohort Studies; D004347:Drug Interactions; D005260:Female; D005449:Fluorenes / Q000494:pharmacology / Q000627:therapeutic use*; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D054328:Proton Pump Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D012189:Retrospective Studies; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use*; D000069474:Sofosbuvir / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D005449:Fluorenes; D054328:Proton Pump Inhibitors; C586541:ledipasvir; D012254:Ribavirin; D000069474:Sofosbuvir