Background/Aims: The natural history and predictors of HCV-related disease
severity post-transplantation are uncertain. The aims of this study were to
define the natural history of post-transplantation HCV infection by assess
ing the rate of fibrosis progression, to determine if the post-transplantat
ion natural history differs from that observed pre-transplantation, and to
identify predictors of post-transplantation disease progression.
Methods: Post-transplantation biopsies (mean: 3+/-1.6/patient) from 284 pat
ients were scored according to histologic stage, using the method of Desmet
et al. Change in fibrosis score (fibrosis progression/year) post-transplan
tation was used as the primary outcome. Predictors analyzed included viral
factors (genotype and viral load at transplantation), patient demographics,
year of transplantation, country of transplantation, pre-transplantation f
ibrosis progression, immunosuppression and laboratory data.
Results: There was a linear association between change in fibrosis score an
d time from transplantation, with a median rate of fibrosis progression per
year of 0.3 (0.004-2.19/year). Using parametric time-to-event analysis, th
e expected median duration to cirrhosis was 10 years. The rate of post-tran
splantation fibrosis progression was significantly higher than pretransplan
tation (0.2/year (0.09-0.8) p<0.0001), and higher in Spanish than US center
s (0.48 (0.01-2.19) vs 0.28 (0.004-2.08); p=0.09) despite similar progressi
on rates prior to transplantation. Variables independently associated with
post-transplantation progression included year of transplantation (p=0.0001
), race (p=0.02), number of methyl-prednisolone boluses (p=0.03), and HCV R
NA levels at transplantation (p=0.01).
Conclusions: HCV-related disease progression is accelerated in immunocompro
mised compared to immunocompetent patients, with a progressive increase in
patients who have recently undergone liver transplantation. Changes in pati
ent management posttransplantation over time and between transplant centers
may account for the increase in fibrosis progression observed in recent ye
ars.