The impact of sirolimus on hepatitis C recurrence after liver transplantation.
BACKGROUND
While some immunosuppression strategies may accelerate hepatitis C virus (HCV) recurrence after liver transplantation (LT), the impact of sirolimus (SRL) is not known.


OBJECTIVE
To assess the risk of biopsy-proven HCV recurrence and patient survival using known and suspected risk factors for HCV recurrence as covariates.


METHODS
A retrospective analysis of 141 consecutive patients, including 88 who received de novo SRL therapy, who had undergone a first LT for HCV cirrhosis was conducted. Known and suspected risk factor covariates including transplant era, donor and recipient age, Model for End-stage Liver Disease score, cold ischemia time, immunosuppressive drugs and steroid treatment rejection rates were used in the assessment.


RESULTS
Overall, 72.3% of the cohort developed biopsy-proven HCV recurrence. The incidence of HCV recurrence was not significantly different for patients treated with SRL (75% versus 69.8%; P=0.5). There was no difference found for time to recurrence, nor did mean activity or fibrosis scores differ at the time of initial recurrence. However, on follow-up using serial biopsies in patients with recurrence, the mean activity and fibrosis scores were significantly lower in the SRL group. Donor age and acute rejection episodes were the only factors affecting the HCV recurrence rate (expB 1.02 [95% CI 1.01 to 1.03]); P=0.03; and expB 2.8 [95% CI 1.8 to 4.3]; P<0.01], respectively). SRL treatment did not alter patient survival rates. Among patients treated with SRL-based immunosuppression, higher drug area under the curve levels were associated with a trend to lower disease activity and fibrosis at diagnosis; however, higher SRL levels were associated with shorter recurrence-free survival (P=0.038).


CONCLUSIONS
Results of the present analysis suggest that de novo SRL-based immunosuppression can be safely used in patients undergoing LT for HCV-associated liver disease; however, SRL-based immunosuppression did not significantly affect the timing or severity of post-transplant HCV recurrence. HCV recurrence in SRL-treated patients had lower progressive activity and fibrosis levels on serial biopsy.
Department of Surgery, University of Alberta, Edmonton, Alberta.
Sonal
S
Asthana
Christian
C
Toso
Glenda
G
Meeberg
David L
DL
Bigam
Andrew
A
Mason
James
J
Shapiro
Norman M
NM
Kneteman
D000328:Adult; D000368:Aged; D065095:Calcineurin Inhibitors; D018450:Disease Progression; D005260:Female; D006526:Hepatitis C / Q000517:prevention & control* / Q000601:surgery; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008103:Liver Cirrhosis / Q000601:surgery* / Q000821:virology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012189:Retrospective Studies; D020123:Sirolimus / Q000627:therapeutic use*
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D020123:Sirolimus
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