University of Modena experience in HIV-positive patients undergoing liver transplantation.

INTRODUCTION: Highly effective antiretroviral therapy in the last decade has increased the survival rates of HIV-positive patients, yielding a greater number of HIV patients suffering from liver-related disease. Liver transplantation (LT) is the only curative treatment for end-stage liver disease (ESLD) associated or not with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: From June 2003 to September 2010, 23 patients underwent cadaveric donor LT for ESLD at our institution. Inclusion criteria followed the Italian Protocol for LT in HIV-positive patients. Immunosuppressive regimens were based on cyclosporine or tacrolimus, eventually switched to Rapamycin. RESULTS: The median CD4 T-cell count was 275/mmc (range=119-924). All patients were affected by ESLD, which was associated with HCC in 14 cases. Ten patients were within the Milan criteria and four patients exceeded them but were within the San Francisco criteria. Conversion from calcineurin inhibitors (CNI) to rapamycin occurred in ten cases. Hepatitis C virus (HCV) recurrence occurred in 13/21 HCV-positive patients. Acute cellular rejection occurred in eight patients with one developing chronic cellular rejection. Overall patient and graft survivals at 80 months were 50% and 45% respectively. DISCUSSION: LT in HIV-positive patients is a feasible procedure, even if in our experience was burdened by a greater incidence of complications including HCV recurrence and infection compared with HIV-negative patients.

Pulmonary hypertension as a predictor of postoperative complications and mortality after liver transplantation.

Most transplant centers consider severe pulmonary hypertension (PHT) to be an absolute contraindication for orthotopic liver transplantation (OLT). We retrospectively examined the outcome of 24 patients with PHT (group 1) who underwent OLT compared with 24 matched patients (group 2) without PHT, who also underwent OLT. Based on right cardiac catheterization measurements made after the induction of anesthesia for OLT, PHT was defined as mild or moderate-to-severe if the mean pulmonary arterial pressure exceeded 25 or 35 mm Hg, respectively. The incidence of PHT was 9.8% (24/244); 21/24 PHT patients showed mild and 3/24 moderate PHT. Kaplan-Meier survival analysis did not show a significant difference between the two groups. The incidence of pulmonary infections was significantly greater in group 1 (P < .05). The duration of ventilation and intensive care unit stay was similar in the two groups. Echocardiography detected only the three moderate cases of PHT and not the twenty-one cases of mild PHT. Our analysis suggested that mild PHT was common and did not affect patient outcomes after OLT; moderate or severe PHT was uncommon. The two patients with moderate PHT survived OLT and did not succum to PHT during long-term follow-up.

Novel genetic mutation in apolipoprotein E2 homozygosis and its implication in organ donation: a case report.

Disorders in lipoprotein metabolism do not contraindicate liver procurement and transplantation (LT). In this circumstance, LT provides an intriguing opportunity to assess the in vivo contribution of the liver to the synthesis and degradation of genetically polymorphic plasma proteins. Apolipoprotein (APO) E exists with several common phenotypic differences due to gene polymorphism. Some authors have shown that the APOE phenotype of the recipient was virtually completely converted to that of the donor, providing evidence that >90% of plasma APOE arises from the liver. Homozygosis for APOE2 (E2-E2) is related to an increased incidence of type III hyperlipoproteinemia (HLP). Recently, some authors have identified 4 new APOE mutations that are strongly linked to a unique entity of renal lipidosis called lipoprotein glomerulopathy (LPG). At present, 65 cases of LPG have been reported worldwide, although most patients have been discovered in Japan and other East Asian countries. We have herein reported a case of LT in a patient with advanced hepatocarcinoma who received a liver from a caucasian donor affected by type III HLP due to homozygous E2-E2. The LPG was due to a novel genetic mutation in APOE. After the LT, the recipient, developed de novo severe lipid abnormalities despite good graft function. To our knowledge this is the first report of an LT using a graft from a non Asian donor with homozygous E2-E2 with the presence of a novel APOE mutation.

Early withdrawal of calcineurin inhibitors and everolimus monotherapy in de novo liver transplant recipients preserves renal function.

We designed a randomized trial to assess whether the early withdrawal of cyclosporine (CsA) followed by the initiation of everolimus (Evr) monotherapy in de novo liver transplantation (LT) patients would result in superior renal function compared to a CsA-based immunosuppression protocol. All patients were treated with CsA for the first 10 days and then randomized to receive Evr in combination with CsA up to day 30, then either continued on Evr monotherapy (Evr group) or maintained on CsA with/without mycophenolate mofetil (CsA group) in case of chronic kidney disease (CKD). Seventy-eight patients were randomized (Evr n = 52; CsA n = 26). The 1-year freedom from efficacy failure in Evr group was 75% versus 69.2% in CsA group, p = 0.36. There was no statistically significant difference in patient survival between the two groups. Mean modification of diet in renal disease (MDRD) was significantly better in the Evr group at 12 months (87.7 ± 26.1 vs. 59.9 ± 12.6 mL/min; p < 0.001). The incidence of CKD stage ≥ 3 (estimated glomerular filtration rate < 60 mL/min) was higher in the CsA group at 1 year (52.2% vs. 15.4%, p = 0.005). The results indicate that early withdrawal of CsA followed by Evr monotherapy in de novo LT patients is associated with an improvement in renal function, with a similar incidence of rejection and major complications.

Liver transplantation in patients aged 65 and over: a case-control study.

INTRODUCTION: The average age of patients undergoing liver transplantation (LT) is consistently increasing. The aim of this case-control study is to evaluate survival and outcome of patients ≥65 yr compared to younger patients undergoing LT. MATERIALS AND METHODS: From 10/00 to 4/08 we performed 330 primary LT, 31 (9.4%) of these were in patients aged 65-70. Following a case-control approach, we compared these patients with 31 patients aged between 41 and 64 yr and matched according to sex, LT indication, viral status, cadaveric/living donor, LT timing, and Model for End-Stage Liver Disease (MELD) score. RESULTS: There were no statistically significant differences in demographic and surgical donor characteristics. The mean MELD score was under 18 in both groups. Post-LT complications occurred with a similar incidence in the two groups. one-, three-, and five-yr survival was 83.9%, 80.6%, and 80.6%, respectively, for the elderly group, and 80.6%, 73.8%, and 73.8%, respectively, for the young group (p = 0.61). DISCUSSION: Patients aged between 65 and 70 with low MELD score who undergo LT have the same short- and middle-term survival expectancy, morbidity, and outcome quality as younger patients with the same indication and same pre-LT pathology severity, whatever they might be. Thus, chronological age alone should not deter LT workup in patients >65 and <70.

Liver transplantation utilizing grafts from donors with genitourinary cancer detected prior to liver implantation.

Expansion of the donor pool has led to reconsideration of selection criteria to obtain the largest number of grafts without compromising recipient outcomes. This reconsideration concerns the utilization of donors with malignancies. Herein we have analyzed the outcomes, survivals, and risks of cancer transmission among patients who received a liver transplant from a donor with a genitourinary malignancy. Six of 363 patients (1.5%) who underwent transplantation at our center received an organ from a donor with a genitourinary cancer which was detected prior to the surgical harvest. Donors affected by low-grade renal cell carcinoma (Fuhrman grade 1 or 2) or low-grade intraprostatic prostate carcinoma (Gleason score

Temporary porto-caval shunt utility during orthotopic liver transplantation.

INTRODUCTION: In liver transplantation (OLT) a porto-caval shunt is a well-defined technique practiced by many surgeons in several centers. METHODS: We considered 186 cadaveric OLT patients who underwent a cavo-cavostomy-type reconstruction; they were divided into two groups: those in whom we performed a porto-caval shunt (group A) and those in whose we did not (group B). We evaluated several variables: warm and total ischemia time, intraoperative blood and fresh frozen plasma transfusions, crystalloid and colloid requirements, blood loss, operative duration, hemodynamic intraoperative changes and diuresis, length of hospital stay, and creatinine values at days 1 and 2, and at discharge day. RESULTS: Total and warm ischemic time differed significantly between the two groups. Infusion of blood, fresh frozen plasma, colloid, and crystalloid did not significantly differ. Blood loss was lower, and intraoperative diuresis was not significantly increased in group A subjects. Postoperative hospitalizations were 16.5 and 17.8 days and operative times, 504 and 611 minutes in the two groups. Both cardiac index and ejection fraction values during the anhepatic phase were significantly greater among group A than group B patients. PAD at the two phases was greater in group B. The PAS was significantly different only at reperfusion time. Creatinine values were significantly different at discharge. Better survival was shown for group A patients over group B subjects. CONCLUSION: The results presented herein confirmed that a porto-caval shunt during OLT was a safe, useful expedient contributing to an improved hemodynamic status and a better time distribution in the various phases of liver transplantation.

Effects of everolimus monotherapy on hematological parameters and iron homeostasis in de novo liver transplant recipients: preliminary results.

INTRODUCTION: Anemia after orthotopic liver transplantation (OLT) is a common complication due to several reasons. Immunosuppressive drugs play an important role in anemia occurring at 1 month or more after OLT. Several studies describe myelosuppression immunosuppressants such as the mammalian target of rapamycin inhibitors. METHODS: We performed a single-center, prospective trial consisting of a short 30-day course of cyclosporine (CsA) associated with everolimus (EVL) from postoperative day 10 (Group EVL) versus a CsA immunosuppressive regimen (Group CsA) in de novo OLT patients. We explored the influence of immunosuppressive drugs on hematological parameters comparing EVL versus CsA. RESULTS: Twenty-eight patients were enrolled in the EVL and 12 in the CsA Groups. After OLT, hemoglobin (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), white blood cell (WBC), platelets (PLT), transferrin saturation (TSAT), iron, ferritin, and transferrin did not differ significantly between the 2 groups at any time point. Among the patients who reached 6-months of follow-up, 5 (41.7%) EVL and 4 (80%) CsA subjects were anemic (P=not significant [NS]). Only anemia in patients enrolled in Group EVL showed a trend toward the features of microcytic, hypochromic anemia. DISCUSSION: Our results demonstrated that de novo anemia in OLT patients treated with EVL monotherapy showed the same incidence as in patients treated with CsA. Hb values remained similar during the entire follow-up. Moreover, overall myelosuppression in the EVL Group was not significantly different from patients in the CsA Group.