Evolution of hepatitis C virus quasispecies immediately following liver transplantation.

Abstract

Liver cirrhosis caused by chronic hepatitis C virus (HCV) infection is the main indication for liver transplantation (LT). There is little information on HCV genetic evolution following transplantation. The aim of this study was to carefully assess early evolution of HCV quasispecies in a cohort of 18 liver transplant recipients followed prospectively. Quasispecies analysis was performed by sequence analysis of the hypervariable region 1 (HVR1) before transplantation and at day 4 and week 4 following LT. A predominant variant was present in 12 (67%) of the 18 patients before transplantation and the same variant was propagated and remained predominant after LT in 6 (50%) of these patients. In the remaining individuals, there were major changes in the quasispecies composition, mostly occurring during the first days after LT. There was a progressive decrease in the nonsynonymous (dN)/synonymous (dS) ratios from baseline (1.2) to day 4 (.6) (P = .08) and to week 4 after LT (.3) (P = .015). Similarly, genetic distance (GD) declined from baseline (.1) to day 4 (.03) (P = .07) and to week 4 (.04) (P = .04). We did not find any differences in HCV genetic evolution between patients with mild (n = 10) or severe (n = 8) disease recurrence. In conclusion, during the first days following transplantation, HCV quasispecies becomes more homogenous, even after major changes in its composition. Importantly, these changes persist and even increase during the 1st month after transplantation. The "bottleneck" effect caused by the implantation of a new graft and the lack of selective pressure due to the strong immunosuppression most likely explain this particular pattern of genetic evolution.