Post-transplant quasispecies pattern remains stable over time in patients with recurrent cholestatic hepatitis due to hepatitis C virus.
OBJECTIVE
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 post-transplant 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.
Doughty
A L
AL
The A.W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Department of Infectious Diseases, University of Sydney, NSW, Australia.
Painter
D M
DM
McCaughan
G W
GW
D000328:Adult; D002779:Cholestasis / Q000601:surgery / Q000821:virology*; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D019698:Hepatitis C, Chronic / Q000601:surgery / Q000821:virology*; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D018807:Polymorphism, Single-Stranded Conformational; D012313:RNA / Q000737:chemistry; D012367:RNA, Viral / Q000032:analysis; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019562:Viral Load; D014764:Viral Proteins / Q000235:genetics
C400562:HVR1 protein, Hepatitis C virus; C034477:RNA primers; D012367:RNA, Viral; D014764:Viral Proteins; D012313:RNA