Effect of different immunosuppressive schedules on recurrence-free survival after liver transplantation for hepatocellular carcinoma.
BACKGROUND
Tumor recurrence represents the main limitation of liver transplantation in patients with hepatocellular carcinoma (HCC) and can be favored by exposure to calcineurin inhibitors.


METHODS
We investigated the effect of an immunosuppressant schedule that minimizes the exposure to calcineurin inhibitors on patients transplanted for HCC to ascertain whether this can reduce the tumor recurrence rate. For this purpose, we conducted a matched-cohort study: 31 patients with HCC transplanted between 2004 and 2007 who received sirolimus as part of their immunosuppression (group A) were compared with a control group of 31 patients (group B) transplanted in the same period who had the same prognostic factors but were given standard immunosuppression based on tacrolimus.


RESULTS
Three-year recurrence-free survival was 86% in group A and 56% in group B (P=0.04). Although the prevalence of microvascular invasion G3-G4 grading and alpha-fetoprotein more than 200 ng/mL was identical in the two groups, exposure to tacrolimus was significantly higher in patients of group B (median, 8.54; range, 5.5-13.5) in comparison with those of group A (median, 4.6; range, 1.8-9.1) (P=0.0001).


CONCLUSIONS
By using sirolimus, exposure to calcineurin inhibitors can be minimized, reducing the risk of HCC recurrence.
Vivarelli
Marco
M
Department of Surgery and Transplantation, University of Bologna, S.Orsola Hospital, Bologna, Italy. marco.vivarelli@aosp.bo.it
Dazzi
Alessandro
A
Zanello
Matteo
M
Cucchetti
Alessandro
A
Cescon
Matteo
M
Ravaioli
Matteo
M
Del Gaudio
Massimo
M
Lauro
Augusto
A
Grazi
Gian Luca
GL
Pinna
Antonio Daniele
AD
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000601:surgery*; D015331:Cohort Studies; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006509:Hepatitis B / Q000150:complications; D006526:Hepatitis C / Q000150:complications; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000209:etiology / Q000601:surgery*; D016031:Liver Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology* / Q000517:prevention & control; D012307:Risk Factors; D020123:Sirolimus / Q000008:administration & dosage / Q000627:therapeutic use*; D017741:Survivors; D016559:Tacrolimus / Q000008:administration & dosage / Q000627:therapeutic use*; D055815:Young Adult
D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D020123:Sirolimus; D016559:Tacrolimus