title: Hepatitis C virus quasi-species dynamics predict progression of fibrosis after liver transplantation.
abstract: BACKGROUND
  The dynamics of hepatitis C virus (HCV) quasi species in the E2 region may correlate with the course of infection after orthotopic liver transplantation (OLT).
  
  
  METHODS
  Thirty-four patients who underwent transplantation for HCV-related cirrhosis were studied. Serum and liver samples were available before OLT and at 1 week, 4 months, and 1 year after OLT. Patients were divided into group 1 (Knodell/Ishak fibrosis stage [FS] at 1 year, <2) and group 2 (FS at 1 year, > or =2). Complexity was estimated by the number of bands in a single-strand conformational polymorphism assay, whereas diversity was measured by Shannon entropy (SE) and median mobility shift (MMS) values derived from the heteroduplex mobility assay. Diversity dynamics were measured at transmission (before OLT vs. 1 week after OLT) and after OLT (1 week after OLT vs. 1 year after OLT).
  
  
  RESULTS
  Complexity was higher in group 1 patients than in group 2 patients before OLT (P<.02) and at 1 week after OLT (P<.04). Diversity decreased in group 1 at transmission, as measured by either SE (P<.01) or MMS (P<.04). However, diversity increased in this group after OLT, as measured by SE (P<.03) or MMS (P<.02). FS at 1 year after OLT correlated with transmission changes, as measured by SE (r=0.642, P<.0001) and MMS (r=0.443, P<.04), and with post-OLT changes (for SE: r=-0.583, P<.01; for MMS: r=-0.536, P<.01).
  
  
  CONCLUSIONS
  HCV complexity and diversity in the E2 region correlated with the severity of recurrence of HCV infection after OLT. Increased diversity of quasi species at transmission correlated with a higher FS at 1 year. However, increased diversity of quasi species in the post-OLT period correlated with a lower FS at 1 year. The dynamics of HCV quasi species in patients who undergo transplantation are predictive of outcome.
authors.affiliation: Division of Transplantation Medicine, Mayo Clinic Scottsdale, Arizona 85259, USA.
authors.forename: Juan I
authors.initials: JI
authors.lastname: Arenas
authors.forename: Juan F
authors.initials: JF
authors.lastname: Gallegos-Orozco
authors.forename: Tomasz
authors.initials: T
authors.lastname: Laskus
authors.forename: Jeff
authors.initials: J
authors.lastname: Wilkinson
authors.forename: Amer
authors.initials: A
authors.lastname: Khatib
authors.forename: Carlos
authors.initials: C
authors.lastname: Fasola
authors.forename: Debra
authors.initials: D
authors.lastname: Adair
authors.forename: Marek
authors.initials: M
authors.lastname: Radkowski
authors.forename: Karen V
authors.initials: KV
authors.lastname: Kibler
authors.forename: Marek
authors.initials: M
authors.lastname: Nowicki
authors.forename: David
authors.initials: D
authors.lastname: Douglas
authors.forename: James
authors.initials: J
authors.lastname: Williams
authors.forename: George
authors.initials: G
authors.lastname: Netto
authors.forename: David
authors.initials: D
authors.lastname: Mulligan
authors.forename: Goran
authors.initials: G
authors.lastname: Klintmalm
authors.forename: Jorge
authors.initials: J
authors.lastname: Rakela
authors.forename: Hugo E
authors.initials: HE
authors.lastname: Vargas
mesh_terms: D020121:5' Untranslated Regions / Q000737:chemistry / Q000235:genetics; D018450:Disease Progression; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D014644:Genetic Variation; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000601:surgery / Q000821:virology*; D006801:Humans; D008103:Liver Cirrhosis / Q000276:immunology / Q000821:virology*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D018807:Polymorphism, Single-Stranded Conformational; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics
chemical_list: D020121:5' Untranslated Regions; D012367:RNA, Viral; D014759:Viral Envelope Proteins