Complete weaning off immunosuppression in HCV liver transplant recipients is feasible and favourably impacts on the progression of disease recurrence.
OBJECTIVE
HCV-related disease recurrence progresses rapidly after liver transplantation. We hypothesised that withdrawal of immunosuppression might favourably impact on disease progression.


METHODS
Weaning off immunosuppression was attempted in 34 HCV-RNA positive patients (mean age 62+/-6.4 years) transplanted 63.5+/-20.1 months earlier, under cyclosporine A monotherapy. Patients were followed for 3 years including yearly protocol liver biopsies. Primary endpoints were feasibility of weaning off immunosuppression and its impact on disease progression. Secondary endpoint was to identify predictors of an immunosuppression-free state and fibrosis progression.


RESULTS
Complete and permanent immunosuppression withdrawal was achieved in 8 patients (23.4%), whereas 14 (41.2%) developed rejection within eight months despite an initial response and 12 (35.2%) rejected during tapering. After a mean follow-up 45.5+/-5.8 months weaned patients showed stabilisation/improvement of histological fibrosis (P<0.01), lower necro-inflammation (P<0.02) and improved liver function (P<0.05) compared to weaning-intolerants. Multiple logistic regression identified low blood cyclosporine A trough levels during the first post-transplant week (P=0.004) and initial steroid-free immunosuppression (P<0.008) as independent predictors of sustained weaning. Achievement of immunosoppression freedom (P=0.02) and baseline staging score (P<0.0001) were independently associated with stabilisation/improvement of histological fibrosis.


CONCLUSIONS
Reconstitution of immune-competence in the host improves the natural history of HCV recurrence in the graft.
Tisone
Giuseppe
G
Liver Transplant Unit, Surgical Clinic, University of Rome Tor Vergata, S. Eugenio Hospital, Viale dell'Umanesimo 10, 00144, Rome, Italy. tisone@med.uniroma2.it
Orlando
Giuseppe
G
Cardillo
Andrea
A
Palmieri
Giampiero
G
Manzia
Tommaso Maria
TM
Baiocchi
Leonardo
L
Lionetti
Raffaella
R
Anselmo
Alessandro
A
Toti
Luca
L
Angelico
Mario
M
D000368:Aged; D016572:Cyclosporine / Q000276:immunology / Q000627:therapeutic use; D018450:Disease Progression; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology; D006526:Hepatitis C / Q000188:drug therapy* / Q000601:surgery*; D006801:Humans; D007121:Immunocompetence / Q000502:physiology; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000276:immunology; D008099:Liver / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology / Q000821:virology; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D012008:Recurrence; D012044:Regression Analysis
D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D012367:RNA, Viral; D016572:Cyclosporine