title: Hepatitis C genotype influences post-liver transplant outcomes.
abstract: BACKGROUND
  In nontransplant patients with chronic hepatitis C virus (HCV), HCV genotype has been linked with a differential response to antiviral therapy, risk of steatosis and fibrosis, as well as all-cause mortality, but the role of HCV genotypes in posttransplant disease progression is less clear.
  
  
  METHODS
  Using the multicenter CRUSH-C cohort, genotype-specific rates of advanced fibrosis, HCV-specific graft loss and response of antiviral therapy were examined.
  
  
  RESULTS
  Among 745 recipients (605 [81%] genotype 1, 53 [7%] genotype 2, and 87 [12%] genotype 3), followed for a median of 3.1 years (range, 2.0-8.0), the unadjusted cumulative rate of advanced fibrosis at 3 years was 31%, 19%, and 19% for genotypes 1, 2, and 3 (P = 0.008). After multivariable adjustment, genotype remained a significant predictor, with genotype 2 having a 66% lower risk (P = 0.02) and genotype 3 having a 41% lower risk (P = 0.07) of advanced fibrosis compared to genotype 1 patients. The cumulative 5-year rates of HCV-specific graft survival were 84%, 90%, and 94% for genotypes 1, 2, and 3 (P = 0.10). A total of 37% received antiviral therapy, with higher rates of sustained virologic response in patients with genotype 2 (hazard ratios, 5.10; P = 0.003) and genotype 3 (hazard ratios, 3.27; P = 0.006) compared to patients with genotype 1.
  
  
  CONCLUSIONS
  Risk of advanced fibrosis and response to therapy are strongly influenced by genotype. Liver transplantation recipients with HCV genotype 1 have the highest risk of advanced fibrosis and lowest sustained virologic response rate. These findings highlight the need for genotype-specific management strategies.
authors.affiliation: 1 Division of Gastroenterology and Hepatology, University of California-San Francisco, San Francisco, CA. 2 Division of Gastroenterology and Hepatology, New York Presbyterian Hospital-Columbia, New York, NY. 3 Baylor Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX. 4 Section of Hepatology and Hume-Lee Transplant Center, Virginia Commonwealth University, Richmond, VA. 5 Division of Hepatology, University of Colorado, Denver, CO.
authors.forename: Isabel
authors.initials: I
authors.lastname: Campos-Varela
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Lai
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Verna
authors.forename: Jacqueline G
authors.initials: JG
authors.lastname: O'Leary
authors.forename: R
authors.initials: R
authors.lastname: Todd Stravitz
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Forman
authors.forename: James F
authors.initials: JF
authors.lastname: Trotter
authors.forename: Robert S
authors.initials: RS
authors.lastname: Brown
authors.forename: Norah A
authors.initials: NA
authors.lastname: Terrault
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006085:Graft Survival; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000601:surgery* / Q000821:virology; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D012367:RNA, Viral / Q000097:blood; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral