2010 - TTS International Congress


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Immunosuppression for Liver Transplantation

91.5 - Single centre experience in conversion of calcineurin inhibitor to sirolimus-based immunosuppression following liver transplantation.

Presenter: Simon, Harper, Cambridge,
Authors: Harper S., Gelson W., Harper I., Alexander G., Gibbs P.

SINGLE CENTRE EXPERIENCE IN CONVERSION OF CALCINEURIN INHIBITOR TO SIROLIMUS-BASED IMMUNOSUPPRESSION FOLLOWING LIVER TRANSPLANTATION.

IMMUNOSUPPRESSION FOR LIVER TRANSPLANTATION

S. Harper1, W. Gelson1, I. Harper2, G. Alexander1, P. Gibbs1
1, Cambridge University, Cambridge/UNITED KINGDOM, 2Department Of Surgery, Addenbrooke's Hospital, University of Cambridge, Cambridge/UNITED KINGDOM

Body: Introduction The use of sirolimus remains limited in liver transplantation in comparison with renal transplantation. The potential advantage of the low nephrotoxicity of sirolimus balances against significant side effects. The aim of this study is to report extensive experience in conversion of CNI to sirolimus-based immunosuppression in liver transplantation. Methods A retrospective review of 148 patients converted from CNI to sirolimus following liver transplantation was undertaken using patient records. Results Ninety-four patients were male and 54 female and the median age was 61 years old. The most common indications for transplantation were hepatitis C virus (HCV) (33%) and alcoholic liver disease (23%). The most common indications for sirolimus use were renal impairment (52%), HCV (32%) and CNI intolerance (9%). One hundred and eleven (75%) patients remained on sirolimus after median follow up of 1006 days (range 30 – 2759). The mean (+/- S.D.) GFR of patients just prior to conversion was 59 +/- 29 ml/min increasing to 69 +/- 36, 70 +/- 37 and 72 +/- 39 ml/min at 6 months, 3 years post-conversion and follow up respectively (p<0.05). No significant change in liver function tests, haematological parameters, HbA1C or mean arterial pressure was observed following conversion. Biopsy proven acute rejection occurred in 4 patients following conversion. A total of 112 side effects attributed to sirolimus occurred in 101 (68%) patients and included peripheral oedema (21%), mouth ulceration (15%) and pneumonitis (5%). Sirolimus was withdrawn in 20 patients (14%) due to drug intolerance after a median treatment period of 345 days (range 10 – 2097). Mean serum LDL was 4.4 +/-1.1 mmol/L pre-conversion, increasing to 5.5 +/- 1.3 at 6 months and levelling at 4.9 +/- 0.8 at 5 years (p<0.05). Mean serum triglyceride levels followed a similar pattern. Statins were commenced in 83 (51%) patients. The percentage of patients with detectable proteinuria pre-conversion, 1 month, 6 months and 5 years post-conversion was 45%, 68%, 72%, 58% respectively. Proteinuria was not associated with deterioration in renal function. Pre and post-conversion biopsies were available in 33 patients with HCV over a median follow up of 708 days. Fifteen (45%) patients had documented improvement in terms of liver fibrosis, 13 (39%) were unchanged and 5 (16%) had deteriorated. Conclusions This study demonstrates that in liver transplantation, conversion from calcineurin inhibitor to sirolimus-based immunosuppression results in a significant improvement in renal function unaffected by an increased incidence of proteinuria. Sirolimus-related side effects are common but can usually be managed conservatively. Sirolimus may offer additional benefits in attenuating graft fibrosis in HCV patients.

Disclosure: All authors have declared no conflicts of interest.


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