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

The evolution of hepatitis C virus (HCV) envelope variation was studied usi ng a liver-transplant model to evaluate the role of HCV quasispecies for he patocyte infection. Twelve HCV polymerase chain reaction (PCR)-positive liv er-transplant recipients (6 with posttransplantation biochemical hepatitis and 6 without hepatitis [controls]) were prospectively evaluated and underw ent detailed quasispecies analysis of pre- and postoperative serum samples. HCV amino acid sequence diversity and complexity at the first hypervariabl e region (HVR1) of the second envelope protein (E2) was correlated with out come. Recurrence of HCV-induced allograft injury was defined by persistentl y elevated serum alanine transaminase (ALT) levels. The major variant (sequ ences > 10% of all clones) of recipients with hepatitis accounted for a sig nificantly smaller percent of all preoperative clones compared with control s (41% +/- 6% vs. 69% +/- 8%; P < .015). Recipients with hepatitis had an i ncreased number of pretransplantation major variants (2.5 +/- 0.3 vs. 1.1 /- 0.2; P < .006). Eighty-three percent of controls had a predominant varia nt (accounting for >50% of clones) compared with 17% of those with recurren ce (P < .05). These differences did not persist postoperatively. In additio n, recipients without a pretransplantation predominant variant demonstrated an increased allograft fibrosis score (2.3 +/- 0.3 vs. 0.5 +/- 0.3; P < .0 15) at 181 to 360 days posttransplantation compared with those in whom a pr edominant variant was present, Increased HCV envelope complexity may act as a stronger antigenic stimulus or improve hepatocyte receptor binding and l ead to allograft hepatitis and fibrosis. Although pretransplantation differ ences in HCV quasispecies did not persist postoperatively, pretransplantati on quasispecies may he a predictor of HCV-induced hepatitis and graft fibro sis after liver transplantation.