Background/Aims: 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. (c) 2006 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

The training of the transplant surgeon is one of the most difficult paths in medicine. The transplant surgeon must be trained as a general and a vascular surgeon; he has to be skilled and upgraded in transplant surgical technique; he has to decide the suitability of the donor and of the organs as well as the immunosuppressive therapy for each recipient; he must know the intensive care unit, hepatology, and nephrology. The transplant surgeon has to deal with surgical, infectious, and metabolic complications after organ transplantation. Thus, clinical formation of the transplant surgeon is multifactorial and always upgraded. However, transplants never happen in the morning; retrivals are more likely to be in the night (expecially the holidays ones). "Weekend" is a word not frequently used by transplant surgeons. Morover, when the transplant procedure happens, the normal activity of the ward and of the outpatient clinic were have to be done. The transplant surgeon must have a sort of "vocation" for such a job. Organ harvesting setting is a good proof of adaptability, always during nighttime, often in small hospitals with operating room nurses unfamiliar with the procedure, sometimes waiting for some colleagues or delaying the surgery. This vocation is enhanced by enthusiasm, but incentives are necessary to feed this love. Incentives should be professional and economic; transplant surgeons should be allowed to make clinical decisions, to choose the surgical technique of transplantation, to control the decision process. Lastly, due to the "total on call," the surgeon should profit from a right salary avoiding extramural activities.

Cirrhosis' and complications (a) Pathophysiology $71 Methods: Patients admitted for ALF to Saint-Luc's Hospital liver unit in Montreal between 1991 and 2002 were included in this retrospective study.Clinical and biochemical data were recorded form patients' charts review.During the study period, there was no systematic policy regarding the use of prophylactic antibiotics in patients with ALF in our institution.Patients were divided into two groups according to whether they received prophylactic intravenous antibiotics or not.Statistical analysis was performed using Chi-square, Student's t, Mann Whitney and Log-rank tests as appropriate.Results: 115 patients with ALF were identified.3 patients were excluded from the study because they were infected and treated with antibiotics before their transfer to our unit.Group 1 (no prophylactic antibiotics) included 88 patients and group 2 (prophylactic antibiotics) included 24 patients.The proportion of patients with hyperacute, acute and subacute liver failure was not statistically different in the two groups.The etiology of ALE patient age, gender, INR, creatinine and grade of hepatic encephalopathy on admission did not differ significantly between the two groups.69% of group 1 patients and 71% of group 2 fulfilled King's College Hospital criteria for liver transplantation (p 0.89).51% of group 1 patients developed an infection compared to 33% in group 2 (p 0.12).The cumulative incidence of infection, determined using the Kapla~Meier method, was similar in both groups (72% at 1 month in group 1 and 71% in group 2, p 0.67).A similar proportion of patients of the two groups died, was transplanted or survived without transplantation.Conclusion: Among patients with ALF who received prophylactic intravenous antibiotics, the proportion developing an infection tended to be lower than in patients who did not receive antibiotics but the patients' outcomes were similar.

A 37-year-old male liver transplant recipient developed hemorrhagic shock from massive rectal bleeding a few hours after a protocol liver biopsy. Conservative treatment was not possible and the patient underwent a radiological investigation of the celiac and mesenteric arterial trunks, which showed active bleeding from a branch of the middle colic artery. Embolization with Tabotamp (Ethicon, Neuchatel, CH Switzerland) particles led to successful hemostasis. We thus discuss the possible mechanisms of injury. To our knowledge, no other cases of major rectal bleeding following percutaneous liver biopsy have been reported in the literature. We emphasize the need for Doppler ultrasound assistance, in terms of either preoperative examination with or without marking or guidance. The latter is the safest and most reliable technique, given the low risk of puncture of other organs and the low probability of obtaining an inadequate sample.

Mycophenolate mofetil (MMF) is an immunosuppressive drug, exhibiting its effect through inhibition of proliferation of T and B lymphocytes. Standard primary immunosuppressive therapy after orthotopic liver transplantation (OLT) is based on a calcineurin-inhibitor (CNI): cyclosporine or tacrolimus. Renal failure with arterial hypertension, due to CNI side-effects, is a major cause of morbidity and mortality after OLT. Several studies have shown the efficacy of MMF to improve CNI-induced nephrotoxicity, blood pressure, and uric acid concentration in liver transplant patients with concomitant reduction or withdrawal of CNI. Predose plasma mycophenolic acid concentrations (MPA) are related to adverse events, drug dose, and clinical status. Blood level values outside the suggested MPA therapeutic range are associated with acute rejection episodes and side effects, which have been described in about half of the patients treated with MMF. Most authors have described gastrointestinal and hematological side-effects, whereas these appear usually dose related, responding quickly to reduction.MMF is potent and safe immunosuppressive agent, and replacement of CNI by MMF in liver transplant patients with renal dysfunction may improve not only kidney function but also other CNI-associated side-effects, such as hypertension and hyperuricemia, with a low risk of rejection.

O439 Aims: Long-term side effects of immunosuppressive therapy with calcineurin inhibitors (CNI) in liver transplant patients are major causes of morbidity. Methods: We undertook a prospective study to assess the safety and efficacy of CNI withdrawal and replacement by mycophenolate mofetil. 38 patients with a minimum follow-up of 2 years after liver transplantation were included in the study. They were all on monotherapy of one of the two CNI. Of these 33 had renal dysfunction attributable to suspected CNI toxicity and 5 had hyperlipidaemia. 12 of these patients had both renal dysfunction and hyperlipidaemia. 22 of these patients had also arterial hypertension. Renal function, blood pressure and lipid profile were measured before and 12 months after study entry. A sequential renal scintigraphy was also performed on every patients before and 12 months after study entry, to appraise renal damage and possible improvement. Side effects of medication and graft function were recorded during the study. Results: After 15 months there was a significant decrease in serum creatinine (by 28%) and urea levels (by 36%). Blood pressure improved significantly with a systolic decrease of 20% and diastolic decrease of 12%. There was also an improvement of cholesterol (decrease of 21%) and triglyceride (decrease of 56%). None of the patients had to stop the study because of side effects of the new therapy. No episodes of active graft rejection occurred during the convertion period and after remaining on mycophenolate mofetil monotherapy. Conclusions: Substitution of CNI by mycophenolate mofetil can improve renal function, blood pressure and cholesterol and triglyceride concentration of liver transplant patients without an increased rejection risk with mycophenolate mofetil monotherapy.