Hepatitis C virus quasi-species dynamics predict progression of fibrosis after liver transplantation.
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.
Arenas
Juan I
JI
Division of Transplantation Medicine, Mayo Clinic Scottsdale, Arizona 85259, USA.
Gallegos-Orozco
Juan F
JF
Laskus
Tomasz
T
Wilkinson
Jeff
J
Khatib
Amer
A
Fasola
Carlos
C
Adair
Debra
D
Radkowski
Marek
M
Kibler
Karen V
KV
Nowicki
Marek
M
Douglas
David
D
Williams
James
J
Netto
George
G
Mulligan
David
D
Klintmalm
Goran
G
Rakela
Jorge
J
Vargas
Hugo E
HE
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
D020121:5' Untranslated Regions; D012367:RNA, Viral; D014759:Viral Envelope Proteins