title: Role of replicative senescence in the progression of fibrosis in hepatitis C virus (HCV) recurrence after liver transplantation.
abstract: BACKGROUND
  Although hepatitis C virus (HCV) recurrence is almost universal after orthotopic liver transplantation (OLT), the impact of viral infection on liver graft is highly variable and difficult to predict. Because of the possible relationship between replicative senescence (RS) and the accelerated development of liver fibrosis, we aimed to assess the potential role of RS in the severity of HCV-related chronic hepatitis recurrence after OLT.
  
  
  METHODS
  One hundred three liver biopsies from 56 patients receiving transplants for HCV-related cirrhosis were studied, including 30 revascularization biopsies and 52 and 21 biopsies performed during and beyond the first year of OLT, respectively. The presence of senescent cells in liver grafts was assessed by the senescence-associated beta-galactosidase (SA-beta-Gal) staining method. Chronic hepatitis was defined by fibrosis stage and necrotico-inflammatory activity grade using the METAVIR score.
  
  
  RESULTS
  A total of 34 of the 103 (33%) frozen liver biopsies displayed SA-beta-Gal-positive cells, including 6 (20%) of the revascularization biopsies, 14 (34%) of the biopsies performed within the first year, and 10 (46%) of the biopsies performed beyond 1 year of follow-up. The presence of senescent cells in revascularization biopsies was significantly associated with the degree of ischemic necrosis at time of OLT (P = 0.01) and hepatitis C recurrence in the first year after OLT (P = 0.05). Furthermore, the presence of RS in the biopsy performed within the first year was associated with further development of fibrosis (P = 0.05).
  
  
  CONCLUSIONS
  These data show that RS has a significant impact upon the course of liver transplantation, especially in the long-term progression of fibrosis observed in HCV-infected patients.
authors.affiliation: Service d'Anatomie Pathologique, Hôpital Beaujon, Clichy, France.
authors.forename: Viviane
authors.initials: V
authors.lastname: Trak-Smayra
authors.forename: Jorge
authors.initials: J
authors.lastname: Contreras
authors.forename: Federica
authors.initials: F
authors.lastname: Dondero
authors.forename: François
authors.initials: F
authors.lastname: Durand
authors.forename: Sylvie
authors.initials: S
authors.lastname: Dubois
authors.forename: Daniel
authors.initials: D
authors.lastname: Sommacale
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
authors.forename: Jacques
authors.initials: J
authors.lastname: Belghiti
authors.forename: Claude
authors.initials: C
authors.lastname: Degott
authors.forename: Valérie
authors.initials: V
authors.lastname: Paradis
mesh_terms: D000328:Adult; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000150:complications*; D022781:Hepatocytes / Q000473:pathology; D006801:Humans; D007511:Ischemia / Q000473:pathology; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008102:Liver Circulation; D008103:Liver Cirrhosis / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery / Q000821:virology*; D016031:Liver Transplantation; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D020556:Neutrophil Infiltration; D011183:Postoperative Complications; D012008:Recurrence; D013997:Time Factors; D014779:Virus Replication; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D001616:beta-Galactosidase