Pretransplantation hepatitis C virus quasispecies may be predictive of outcome after liver transplantation

Shawn J. Pelletier, Daniel P. Raymond, Traves D. Crabtree, Julia C. Iezzoni, Robert G. Sawyer, Young S. Hahn, Timothy L. Pruett

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)375-381
Number of pages7
Issue number2
StatePublished - 2000


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