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Background. Ischemia-reperfusion injury is a major cause of early graft dysfunction after liver transplantation. Tauroursodeoxycholic acid (TUDCA), a natural amidated hydrophilic bile salt, protects from cholestasis and hepatocellular damage in a variety of experimental models, as well as from ischemia-reperfusion injury. We investigated in the human liver transplantation setting the effect of the addition of TUDCA at time of liver harvesting and cold storage on the intraand postoperative enzyme release and liver histopathology at the end of cold storage, at reperfusion, and 7 days after transplantation. Methods. Eighteen patients undergoing elective liver transplantation were studied, including 6 serving as controls. In six patients, TUDCA was added to the University of Wisconsin solution used during harvesting and cold storage, to reach final concentrations of 2 mM. In three of these patients, TUDCA (3 g) was infused in the portal vein of the donor before organ explantation; in the other three cases, TUDCA was given through both routes. Results. The use of TUDCA did not cause adverse events. The release of aspartate aminotransferase in the inferior vena cava blood during liver flushing was significantly lower (P=0.05) in TUDCA-treated than in control grafts, as were cytolytic enzyme levels in peripheral blood during the first postoperative week (P

BACKGROUND: Corticosteroids are commonly used in the immunosuppression therapy after liver transplantation, yet are associated with considerable side effects. Retrospective studies have shown that corticosteroids can be safely withdrawn from months to years after transplant. We prospectively investigated the effects of early immunosuppression without the use of corticosteroids on graft outcome and transplant complications. METHODS: Forty-five patients undergoing liver transplantation were randomized to receive immunosuppression composed of cyclosporine microemulsion and azathioprine with (n=22) or without prednisone (n=23), in conventional doses. In those patients who received prednisone, this was withdrawn within 3 months after transplant. The median follow-up of survivors was 14 months (range: 6-24). The study end points were to determine graft survival and function, infectious complications, including hepatitis C virus (HCV)-RNA levels in HCV-infected recipients, acute rejection, kidney function, and metabolic complications. RESULTS: Eleven deaths occurred, 6 of which were in the prednisone group. Two-year survival did not differ between patients treated with or without prednisone (70.2% vs. 78.3%, P=0.83), nor did the causes of death. No differences were observed with regard to graft function, renal function, and infectious complications. In the subset of patients who received transplants for HCV-related cirrhosis, the dynamics of virus replication HCV-RNA was faster among those treated with prednisone. The incidence and severity of acute rejection was similar in the two groups. More than 80% of acute rejections in both groups were classified as mild or moderate and underwent spontaneous resolution. Only two patients in each group had severe acute rejection requiring additional treatment with high-dose steroids. Patients receiving prednisone tended to have greater biochemical signs of cholestasis, higher serum cholesterol and glucose levels, and more frequent insulin requirement than those treated without corticosteroids. CONCLUSIONS: Liver transplantation can be performed safely without using corticosteroids in the early postoperative course, and there is no need for routine aggressive steroid treatment of established acute rejections.

Glycogen storage diseases (GSD) are inherited metabolic disorders of glycogen metabolism due to intracellular enzyme deficiency resulting in abnormal storage of glycogen in tissues. GSD represents an indication for liver transplantation (OLT) when medical treatment fails to control the metabolic dysfunction and/or there is an high risk of malignant transformation of hepatocellular adenomas (HCA). Herein we have reported two cases of GSD, type Ia and type VI, which were both associated with rapidly growing HCA, and underwent OLT because of suspect changes in their radiological features. Final histological findings in the explanted liver showed the presence of hepatocellular carcinoma (HCC) in both cases. In GSD type Ia and VI, OLT is considered to be the treatment of choice when a liver neoplasm is suspected. While the association of HCC with GSD type Ia is well known, this is the first case of HCC in GSD type VI so far reported to the best of our knowledge.

Advagraf is a new modified-release once-daily formulation of tacrolimus. The aim of this study was to define the efficacy and safety of switching from Prograf to Advagraf immunosuppression in kidney transplant recipients. The switched dose ratio of Prograf to Advagraf was 1:1. Forty-one patients (34 men and 7 women) were switched at 36.6 ± 16.1 months after kidney transplantation. All patients maintained stable renal function and the conversion. In 16 subjects it was possible to withdraw steroid administration after obtaining adequate Advagraf blood levels, among whom 14 remained steroid free. Adverse events, including dizziness and tinnitus, were reported in 1 patient, who was reverted to Prograf. One patient who was receiving triple therapy with low tacrolimus blood levels experienced are acute rejection episode. The switch to Advagraf was safe and efficacious in kidney transplant recipients with or without steroid administration. Moreover, interruption of steroid was possible and well tolerated after achieving adequate stable blood levels with Advagraf.

Herein, we report the case of a 52-year-old man with a spermatic cord liposarcoma that developed 4 years after renal transplantation. The patient was admitted with a diagnosis of inguinal hernia. During surgical exploration, a solid mass was found arising from the spermatic cord. Histologic analysis demonstrated a well-differentiated sclerosing liposarcoma.

Liver transplantation is a life-saving procedure for end-stage liver disease. In liver transplant recipients, morbid obesity influences post-operative survival and graft function. In 1996, our patient underwent a successful liver transplantation because of a HCV-related liver failure (body mass index (BMI) 31). Follow-up showed a functional graft and the development of severe obesity up to a BMI of 61 in January 2006. In January 2007, he was submitted to intragastric balloon therapy for 6 months, reaching a BMI of 54. In September 2007, he underwent a biliopancreatic diversion. During follow-up to March 2008, he reached a BMI of 42 with ameliorations of comorbidities. In May 2008, during a hospital admission, he suddenly died of a heart attack. Post mortem study revealed a myocardial infarction. This is the first world case report for this approach. According to our opinion, patient's death was not related to bariatric surgery.

The hemolytic uremic syndrome (HUS) is a severe disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. We herein report our experience with a 43-year-old female patient who underwent a second cadaveric kidney transplantation in February 2005, for adult-onset HUS. The first renal transplantation, which was performed in 1996, required removal after 3 weeks for probable recurrence of HUS. The immunosuppressive regimen for the second transplant included basiliximab, tacrolimus, mycophenolate mofetil, and steroids. On postoperative day (POD) 7, she received steroid treatment for an acute rejection episode with improved renal function. On POD 19 due to worsening renal function, a graft biopsy showed HUS recurrence, thus we instituted hemodialysis and then plasmapheresis treatments. At two months after transplantation, the patient continued under plasmapheresis treatment due to clinical evidence of HUS. On POD 80, cytomegalovirus infection was diagnosed and intravenous gancyclovir treatment started for 3 weeks. After 110 days from transplant, a deterioration in renal function was evident: the graft was swollen and painful with Doppler ultrasound showing patency of both the renal artery and vein but, low blood flow. After 2 weeks of hemodialysis, the patient underwent transplantectomy. In adult-onset HUS the recurrence rate reduces graft survival, particularly among patients undergoing second transplantation.

Biliary lipids output is reduced after liver transplantation and tends to normalize thereafter. Cyclosporine A (CyA) is reported to interfere with the normal bile-restoring process after liver grafting, but data are inconclusive, in particular regarding the comparison with the other widely used calcineurin inhibitor tacrolimus (TCR). Furthermore, previous researches were conducted in patients taking multiple immunosuppressive therapies and with a short follow up. In this study we readdressed this issue by comparing biliary lipids in the first 3 months after liver transplant, in 20 patients randomized to receive immunosuppression with CyA or TCR monotherapy. Bile samples, harvested through a T-tube at days 1, 3, 7, 15, 30, 60 and 90 were assessed for cholesterol, phospholipids, and total and individual concentrations of bile acids (BA). Liver and kidney function tests were evaluated as well. We found no differences between CyA and TCR in biochemical findings or in total biliary BAs, cholesterol, and phospholipids. However, CyA-treated patients showed lower levels of glycochenodeoxycholic acid at day 15, compared to those treated with TCR (P < 0.04). This difference normalized thereafter, without any biochemical or clinical effect at 3-month follow up.

Background In gallbladder bile, lipids aggregate as micelles and vesicles, yet the presence of lamellae remains controversial. Little is known on lipid assembly in dilute hepatic bile. Liver transplantation represents a condition in which bile is diluted immediately after transplant and tends to normalize thereafter. Aim To study biliary lipidic carriers after liver transplantation in relation to the increasing bile lipid concentration. Methods Three bile samples were harvested from six patients (3M/3F) with normal post-transplant outcome: sample 1 at days 2–3, sample 2 at 1 week, and sample 3 at 2 weeks after transplant. Samples were analyzed by biochemical, morphological and quasi-elastic light scattering methodology. Results Lipid concentration increased from 0.6 g/dl at day 2–3 to 3.6 g/dl at week 2. Electron microscopy showed the presence of unilamellar vesicles in all samples. Large amorphous particles interpreted as proteic aggregates were also present at day 2–3, while lamellae coexisted with vesicles later. Quasi-elastic light scattering data were consistent with electron microscopic findings. Liquid crystals were observed at polarizing microscopy with increasing bile lipid concentration. Conclusions Normalization of biliary lipid secretion after liver transplantation is associated with: (i) increased proportion of vesicles and reduction of their size; (ii) presence of lamellae.

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.

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.

s of the 46th A.I.S.F. Annual Meeting 2013 / Digestive and Liver Disease 45S (2013), S1–S48 S7 the increase of HRR. The analysis of survival benefit comparing the risk of waiting list drop-out with the mortality of the 170 transplanted patients with same HRR, showed an important benefit for LT in patients with HRR>16.3. Conclusions: In patients with MELD

Background: To avoid Calcineurin Inhibitor (CI) nephrotoxicity, a CI-freeprotocol was introduced in our centre, as immunosuppressive therapy (IT) indual kidney transplantation (DKT) from marginal donors.Methods: Donor kidneys were histologically evaluated according to Remuzziscore (J Am Soc Nephrol 1999). Fifteen DKT were performed since February2009 with the following IT: basiliximab, steroids, mycophenolate sodium(1440 mg/die), sirolimus (n = 12) or everolimus (n = 3). Mean age of recipientswas 66 years (range 61-71) whereas mean donors age was 68.5 years (range55-78). All patients were analyzed for donor specific HLA-antibodies (HLA-DSA) by solid phase Luminex Single Antigen bead assay, at 1 and 6 monthsfrom KT and then yearly.Results: Median follow up was 35.7 months (range 1-73). Cumulativeincidence of acute rejection (AR) was 33.3% (5/15). ARs were biopsy proven,within 90 postoperative days and responsive to steroids treatment. The mediancreatinine at last follow-up was 1.5 mg/dl (range 0.8-2.8). Steroids werestopped in 7 recipients due to new onset diabetes. No deaths or graft lossesoccurred throughout the follow-up. No patient developed HLA-DSA throughoutthe follow-up.Discussion/Conclusions: AR episodes occurred when recipients wereunder-immunosuppressed for IT adverse events: sirolimus/everolimus bloodlevel under 5 ng/ml (n = 3), early steroid withdrawal (n = 1), or during acutetubular necrosis (n = 1). In our experience CI free IT provides good results inDKT, with excellent long term graft function. Special care should be taken insuch aged recipients with several comorbidity factors. Dual KT is oftenperformed with low HLA compatibility and adequate IT should be constantlyachieved. Hence we recommend sirolimus/everolimus trough levels on the highside of their therapeutic range in the first 6 months post KT.

Background: The once-daily (QD) formulation of tacrolimus (Tac) showedsimilar efficacy than twice-daily (BD) Tac and seems to improve adherence inkidney transplant (KT) recipients. The aim of our study was to define theefficacy and the safety of "de novo" QD Tac administration in KT recipients whoshowed pre KT high panel reactive antibodies (PRA).Methods: Twentyeight patients with a median PRA of 88.3%(range 64-100)who underwent KT were enrolled in the study. Patients were transplanted with anegative crossmatch performed using both cytotoxic and flow-cytom etricmethods. All patients received following immunosuppress ion: basiliximab,steroids, QD-Tac based at 0.2 mg/kg to reach a trough levels of 7-10 ng/mL;27 patients received mycophenolate and one everolimus also. All patients wereanalyzed for donor specific HLA-antibodies (HLA-DSA) by solid phase LuminexSingle Antigen bead assay, at 1 and 6 months from KT and then yearly.Results: Median follow-up was 26.4 months (range 2-57). The 3 yearspatients and graft survival were 100%. The median creatinine at last follow-upwas 1.5 mg/dl (range 0.9-3.1); no patients showed proteinuria. One patientexperienced acute rejection (category 4 IIA Banff '07) at POD 9; after steroidsbolus he was switched to BD Tac because the difficulties to achieve atherapeutic Tac level. No patient developed HLA-DSA throughout the follow up.Conclusion: QD formulation of Tac showed excellent graft and patientsurvival also in highly sensitized patients. A careful care is mandatory in earlyKT to achieve a therapeutic trough Tac levels.

Prednisone has been commonly considered the mainstay of immunosuppressive therapy after liver transplantation. Recent data suggest that prednisone withdrawal late after transplant reduces complications without affecting graft function. We report here the preliminary results of an open-label, randomized study aimed at investigating whether prednisone therapy can be completely avoided during the first 3 months after transplantation. Twenty-seven consecutive patients were randomized to receive double (group A: cyclosporine and azathioprine) or triple (group B: prednisone, cyclosporine, and azathioprine) immunosuppressive therapy after liver transplantation. Six patients died within the first 3 weeks in each group and were excluded from the calculations. The present results refer to 10 patients in group A and 11 in group B. The actuarial 1-year survival did not differ between the two groups (90.9% vs 88.8%). There were no differences with respect to infectious complications or episodes of histological acute graft rejections. Only one severe acute rejection occurred in group A and two in group B. During the first month after transplant, liver and kidney functions tended to be better in the group of patients treated without prednisone, although there were no differences in the mean cyclosporine blood levels. These data, though preliminary, indicate that early immunosuppression without the use of prednisone is safe and tends to be associated with improved liver and renal functions compared to conventional triple therapy.

In order to reduce bleeding, various surgical maneuvers and devices have been used and radiofrequency (RF)-assisted liver resections have been recently advocated by many authors. We performed a right hemihepatectomy for colorectal liver metastases by using new radiofrequency generator (Surtron SB®) combined with hanging maneuver to facilitate the application of the probe and avoid injuries of the interior vena cava (IVC). Operative time was 245 minutes, intraoperative blood loss was 120 ml, transection blood loss was 70 mL. No blood units were administered at any time. After a regular postoperative (PO) course patient was discharged on 11th PO day with normal liver function tests. In conclusion combined use of a RF generator and hanging maneuver in right hemihepatectomy provide bloodless parenchymal transection. The enhanced exposure contributes to better hemostasis and permits the best allocation of the comb with protection of the IVC from injuries.

THE VENO-VENOUS bypass (VVBP) was introduced in orthotopic liver transplantation (OLTx) to prevent venous stasis in the caval compartment and splanchnic venous pooling during the anhepatic phase. VVBP has made OLT an easier procedure by stabilizing patient hemodynamics; decreasing blood losses; and reducing third space fluid losses, visceral edema, and splanchnic venous pooling. Various alternative techniques have been described for establishing the VVBP. The aim of this prospective randomized study was to compare the results of the percutanous technique versus the traditional open surgical technique in terms of hemodynamics, performance, complications, and operating time in a series of 40 consecutive OLTx performed on 39 patients in our Transplant Unit.