Pretransplantation hepatitis C virus quasispecies may be predictive of outcome after liver transplantation.
The evolution of hepatitis C virus (HCV) envelope variation was studied using a liver-transplant model to evaluate the role of HCV quasispecies for hepatocyte infection. Twelve HCV polymerase chain reaction (PCR)-positive liver-transplant recipients (6 with posttransplantation biochemical hepatitis and 6 without hepatitis [controls]) were prospectively evaluated and underwent detailed quasispecies analysis of pre- and postoperative serum samples. HCV amino acid sequence diversity and complexity at the first hypervariable region (HVR1) of the second envelope protein (E2) was correlated with outcome. Recurrence of HCV-induced allograft injury was defined by persistently elevated serum alanine transaminase (ALT) levels. The major variant (sequences >10% of all clones) of recipients with hepatitis accounted for a significantly smaller percent of all preoperative clones compared with controls (41% +/- 6% vs. 69% +/- 8%; P <.015). Recipients with hepatitis had an increased number of pretransplantation major variants (2.5 +/- 0.3 vs. 1.1 +/- 0.2; P <.006). Eighty-three percent of controls had a predominant variant (accounting for >50% of clones) compared with 17% of those with recurrence (P <.05). These differences did not persist postoperatively. In addition, recipients without a pretransplantation predominant variant demonstrated an increased allograft fibrosis score (2.3 +/- 0.3 vs. 0.5 +/- 0.3; P <.015) at 181 to 360 days posttransplantation compared with those in whom a predominant variant was present. Increased HCV envelope complexity may act as a stronger antigenic stimulus or improve hepatocyte receptor binding and lead to allograft hepatitis and fibrosis. Although pretransplantation differences in HCV quasispecies did not persist postoperatively, pretransplantation quasispecies may be a predictor of HCV-induced hepatitis and graft fibrosis after liver transplantation.
Charles O. Strickler Transplant Center, University of Virginia Health Sciences Center, Charlottesville, VA, USA. sjp7t@virginia.edu
S J
SJ
Pelletier
D P
DP
Raymond
T D
TD
Crabtree
J C
JC
Iezzoni
R G
RG
Sawyer
Y S
YS
Hahn
T L
TL
Pruett
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D005260:Female; D016174:Hepacivirus / Q000737:chemistry / Q000302:isolation & purification*; D006526:Hepatitis C / Q000150:complications; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D014184:Transplantation, Homologous; D014759:Viral Envelope Proteins / Q000737:chemistry*
D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus; D000410:Alanine Transaminase