Sj. Pelletier et al., Hepatitis C-induced hepatic allograft injury is associated with a pretransplantation elevated viral replication rate, HEPATOLOGY, 32(2), 2000, pp. 418-426
Hepatitis C virus (HCV) allograft infection after liver transplantation fol
lows a variable but accelerated course compared with the nontransplantation
population. Predictors of outcome and mechanisms of reinfection remain elu
sive. The accelerated HCV-induced allograft injury associated with a 10- to
20-fold increase in serum viral quantity posttransplantation was hypothesi
zed to be the result of elevated intrahepatic viral replication rates. Pati
ents (N = 23) with HCV-induced end-stage liver disease who underwent liver
transplantation between October 1995 and December 1998 were prospectively s
tudied. HCV-induced allograft injury was defined by posttransplantation per
sistent biochemical hepatitis or allograft fibrosis not explained by other
diagnoses. Liver biopsies (N = 92) were obtained by protocol and when clini
cally indicated. Negative-strand HCV RNA (putative intermediate for replica
tion) was detected by a strand-specific reverse-transcription polymerase ch
ain reaction (RT-PCR) assay and semiquantatively compared with constitutive
ly expressed 18S rRNA. Recipients with increased pretransplantation replica
tion were at increased risk for the development of posttransplantation bioc
hemical hepatitis (P = .03), an increased rate of allograft fibrosis (P = .
006), and increased mortality rate (40.0% vs. 0.0%; P = .02). There was no
correlation with quantities of genomic HCV RNA in the serum with relative i
ntrahepatic viral replication either before or after liver transplantation.
The relative rate of HCV replication within the allograft was not elevated
in the posttransplantation period compared with that seen within the expla
nted liver. Accelerated allograft injury caused by HCV may be predicted by
viral replication rates within the explanted liver. The stable intrahepatic
replication rate after transplantation suggests that elevated serum viral
loads are the result of decreased viral clearance, possibly secondary to im
munosuppressive therapy.