Post-transplant quasispecies pattern remains stable over time in patients with recurrent cholestatic hepatitis due to hepatitis C virus

Background/Aims: Several studies have shown that cholestatic recurrent hepatitis is associated with very high HCV RNA loads in liver transplant recipients. The aim of this study was to investigate whether a correlation exists between cholestatic hepatitis posttransplant and the population of viral quasispecies. Methods: One hundred and nine serial sera samples were tested from 15 recurrent HCV patients. Four of these patients showed severe cholestatic recurrent hepatitis, 11 patients demonstrated non-cholestatic recurrent hepatitis post-transplant. Quasispecies were detected by RT-PCR amplification of the HVR1 followed by single-stranded conformational polymorphism analysis. Results: Forty-one samples from four cholestatic patients were tested. All four patients showed very stable quasispecies patterns post-transplant. One cholestatic patient also showed a stable quasispecies band pattern following retransplantation, again associated with severe cholestatic hepatitis. Sixty-eight samples were tested from the 11 non-cholestatic patients. In contrast, these patients showed significantly more quasispecies bands than the cholestatic patients. The noncholestatic patients also displayed fluctuating band patterns post-transplant. Serial samples were tested after retransplantation in one non-cholestatic patient, with a fluctuating pattern again seen. There was a negative correlation between the HCV RNA load in serum and the number of quasispecies bands. Conclusions: Stable hepatitis C viral quasispecies associated with persistently high viral load in post-transplant cholestatic hepatitis suggest that viral escape from immune pressures may play a role in the pathogenesis of this condition.