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.
Liver Transplant Unit, Surgical Clinic, University of Rome Tor Vergata, S. Eugenio Hospital, Viale dell'Umanesimo 10, 00144, Rome, Italy. tisone@med.uniroma2.it
Giuseppe
G
Tisone
Giuseppe
G
Orlando
Andrea
A
Cardillo
Giampiero
G
Palmieri
Tommaso Maria
TM
Manzia
Leonardo
L
Baiocchi
Raffaella
R
Lionetti
Alessandro
A
Anselmo
Luca
L
Toti
Mario
M
Angelico
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