title: Optimal timing of hepatitis C treatment for patients on the liver transplant waiting list.
abstract: The availability of oral direct-acting antivirals has altered the hepatitis C virus (HCV) treatment paradigm for both pre-liver transplant (LT) and post-LT patients. There is a perceived trade-off between pre-LT versus post-LT treatment of HCV-treatment may improve liver function but potentially decrease the likelihood of a necessary LT. Our objective was to identify LT-eligible patients with decompensated cirrhosis who would benefit (and not benefit) from pre-LT treatment based on their Model for End-Stage Liver Disease (MELD) scores. We simulated a virtual trial comparing long-term outcomes of pre-LT versus post-LT HCV treatment with oral direct-acting antivirals for patients with MELD scores between 10 and 40. We developed a Markov-based microsimulation model, which simulated the life course of patients on the transplant waiting list and after LT. Simulation of LT integrated data from recent trials of oral direct-acting antivirals (SOLAR 1 and 2), the United Network for Organ Sharing (UNOS), and other studies. The outcomes of the model included life expectancy, 1-year and 5-year patient survival, and mortality. Model-predicted patient survival was validated with UNOS data. We found that, at the national level, treating HCV before LT increased life expectancy if MELD was ≤27 but could decrease life expectancy at higher MELD scores. Depending on the UNOS region, the threshold MELD score to treat HCV pre-LT varied between 23 and 27 and was lower for UNOS regions 3, 10, and 11 and higher for regions 1, 2, 4, 5, 8, and 9. Sensitivity analysis showed that the thresholds were stable.
  
  
  
  Our findings suggest that the optimal MELD threshold below which decompensated cirrhosis patients should receive HCV treatment while awaiting LT is between 23 and 27, depending on the UNOS region. (Hepatology 2017;65:777-788).
authors.affiliation: Massachusetts General Hospital Institute for Technology Assessment, Boston, MA.|Harvard Medical School, Massachusetts General Hospital, Boston, MA.|Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, MA.
authors.forename: Jagpreet
authors.initials: J
authors.lastname: Chhatwal
authors.affiliation: Massachusetts General Hospital Institute for Technology Assessment, Boston, MA.|Harvard Medical School, Massachusetts General Hospital, Boston, MA.
authors.forename: Sumeyye
authors.initials: S
authors.lastname: Samur
authors.affiliation: Department of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, GA.
authors.forename: Brian
authors.initials: B
authors.lastname: Kues
authors.affiliation: Department of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, GA.
authors.forename: Turgay
authors.initials: T
authors.lastname: Ayer
authors.affiliation: Department of Health Policy and Management, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA.|University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors.forename: Mark S
authors.identifier: 0000-0001-7885-8574
authors.initials: MS
authors.lastname: Roberts
authors.affiliation: Department of Medicine, Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX.|Houston Veterans Affairs Health Services Research and Development Center of Excellence, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX.
authors.forename: Fasiha
authors.initials: F
authors.lastname: Kanwal
authors.affiliation: Massachusetts General Hospital Institute for Technology Assessment, Boston, MA.|Harvard Medical School, Massachusetts General Hospital, Boston, MA.|Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, MA.
authors.forename: Chin
authors.initials: C
authors.lastname: Hur
authors.affiliation: Department of Health Policy and Management, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA.|University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors.forename: Drew Michael S
authors.initials: DM
authors.lastname: Donnell
authors.affiliation: Harvard Medical School, Massachusetts General Hospital, Boston, MA.|Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, MA.
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Chung
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D058625:End Stage Liver Disease / Q000473:pathology / Q000601:surgery* / Q000821:virology; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000517:prevention & control; D006526:Hepatitis C / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D008390:Markov Chains; D008875:Middle Aged; D011300:Preoperative Care / Q000379:methods; D018570:Risk Assessment; D013997:Time Factors; D066027:Transplant Recipients; D016896:Treatment Outcome; D014850:Waiting Lists
chemical_list: D000998:Antiviral Agents