Evolution of hepatitis C viral quasispecies after liver transplantation.
OBJECTIVE
To determine whether HCV quasispecies diversity correlated positively with liver disease progression after orthotopic liver transplantation (OLT).


METHODS
We studied 11 patients undergoing OLT for HCV-related cirrhosis with recurrent hepatitis C in 2 groups according to the stage of hepatic fibrosis on follow-up. The mild group had stage 1 or 2 fibrosis; the severe group, stage 3 or 4 fibrosis. HCV quasispecies diversity was assessed by cloning and sequencing in pretransplantation and posttransplantation serum samples.


RESULTS
In the mild fibrosis group, intrasample hypervariable region 1 (HVR1) genetic distance and nonsynonymous substitutions increased after OLT, whereas in the severe fibrosis group, these parameters decreased in follow-up. In contrast, intrasample diversity progressed similarly in both groups in the adjacent sequences flanking HVR1. There was an inverse correlation between the stage of hepatic fibrosis and amino acid complexity after OLT. Among all patients, the estimated rate of amino acid change was greater initially and became more constant after 36 months.


CONCLUSIONS
After OLT, a more complex HCV HVR1 quasispecies population was associated with mild disease recurrence. Among those patients with severe recurrent hepatitis C, HCV appeared to be under greater immune pressure. The greatest change in viral amino acid sequences occurred in the first 36 months after OLT.
Lyra
Andre C
AC
Division of Gastroenterology & Hepatology, Department of Internal Medicine and Saint Louis University Liver Center, Saint Louis University School of Medicine, St. Louis, Missouri 63110, USA.
Fan
Xiaofeng
X
Lang
Dorothy M
DM
Yusim
Karina
K
Ramrakhiani
Sanjay
S
Brunt
Elizabeth M
EM
Korber
Bette
B
Perelson
Alan S
AS
Di Bisceglie
Adrian M
AM
D000328:Adult; D000595:Amino Acid Sequence / Q000235:genetics; D005075:Biological Evolution; D005355:Fibrosis; D014644:Genetic Variation; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000150:complications; D006801:Humans; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000473:pathology / Q000821:virology; D016031:Liver Transplantation; D008875:Middle Aged; D010802:Phylogeny; D011184:Postoperative Period; D012367:RNA, Viral / Q000235:genetics; D012008:Recurrence; D012086:Reoperation; D012720:Severity of Illness Index; D014764:Viral Proteins / Q000235:genetics
C400562:HVR1 protein, Hepatitis C virus; D012367:RNA, Viral; D014764:Viral Proteins