Outcome of Transplantation Using Organs From Donors Infected or Colonized With Carbapenem-Resistant Gram-Negative Bacteria.

Donor-derived infections due to multidrug-resistant bacteria are a growing problem in solid organ transplantation, and optimal management options are not clear. In a 2-year period, 30/214 (14%) recipients received an organ from 18/170 (10.5%) deceased donors with infection or colonization caused by a carbapenem-resistant gram-negative bacteria that was unknown at the time of transplantation. Among them, 14/30 recipients (47%) received a transplant from a donor with bacteremia or with infection/colonization of the transplanted organ and were considered at high risk of donor-derived infection transmission. The remaining 16/30 (53%) recipients received an organ from a nonbacteremic donor with colonization of a nontransplanted organ and were considered at low risk of infection transmission. Proven transmission occurred in 4 of the 14 high-risk recipients because donor infection was either not recognized, underestimated, or not communicated. These recipients received late, short or inappropriate posttransplant antibiotic therapy. Transmission did not occur in high-risk recipients who received appropriate and prompt antibiotic therapy for at least 7 days. The safe use of organs from donors with multidrug-resistant bacteria requires intra- and inter-institutional communication to allow appropriate management and prompt treatment of recipients in order to avoid transmission of infection.

The first report of orthotopic liver transplantation in the Western world.

Until the present time, the first experimental liver transplant which led to the development of human liver transplantation is attributed to C. Stuart Welch who performed a heterotopic transplant in the canine species in 1955. In 1956, Jack Cannon is credited with the first animal orthotopic liver transplant although the species was not disclosed. This report is intended to set the historical record straight by acknowledging that Vittorio Staudacher in 1952 was the first to perform a liver transplant in a large animal model.

Fully covered metallic stents in biliary stenosis after orthotopic liver transplantation.

BACKGROUND AND STUDY AIMS: Data from a preliminary study suggested that the placement of a fully covered metal stent may be a valid alternative to surgery in patients who do not respond to standard endoscopic treatment. The aims of the current study were to evaluate the clinical success of self-expandable metallic stents (SEMS) in a large cohort of patients and with a long followup,and the effectiveness of SEMS placement as a first-line procedure. MATERIALS AND METHODS: Between January 2008 and August 2010, 54 consecutive patients with biliary complications following orthotopic liver transplantation were treated with SEMS placement:39 after failure of conventional endoscopic therapy (Group I), and 15 with no previous endoscopic treatment who were undergoing SEMS placement as first-line treatment for complications(Group II). RESULTS: In Group I, resolution after SEMS removal was observed in 71.8% of patients. Mean followup after resolution was 22.1 ±10 months. Recurrence of the complication was observed in 14.3%of patients after a mean of 8.5 months and SEMS migration was observed in 33.3% of patients. In Group II, resolution was observed in 53.3% of patients.Mean follow-up after resolution was 14.4±2.2 months. Recurrence was observed in 25% of patients and SEMS migration was observed in 46.7 %. CONCLUSIONS: For endotherapy of biliary complications after orthotopic liver transplantation, metallic stents should not be used as the primary modality. In patients in whom the standard approach fails, treatment with temporary SEMS placement can solve biliary complications in almost three-quarters of cases; however stent migration(33 %) remains a problem.

Primary and reactivated HHV8 infection and disease after liver transplantation: a prospective study.

Human herpesvirus 8 (HHV8) is pathogenic in humans, especially in cases of immunosuppression. We evaluated the risk of HHV8 transmission from liver donors, and its clinical impact in southern Italy, where its seroprevalence in the general population is reported to be as high as 18.3%. We tested 179 liver transplant recipients and their donors for HHV8 antibodies at the time of transplantation, and implemented in all recipients a 12-month posttransplant surveillance program for HHV8 infection. Of the 179 liver transplant recipients enrolled, 10.6% were HHV8 seropositive before transplantation, whereas the organ donor's seroprevalence was 4.4%. Eight seronegative patients received a liver from a seropositive donor, and four of them developed primary HHV8 infection. Two of these patients had lethal nonmalignant illness with systemic involvement and multiorgan failure. Among the 19 HHV8 seropositive recipients, two had viral reactivation after liver transplantation. In addition, an HHV8 seronegative recipient of a seronegative donor developed primary HHV8 infection and multicentric Castleman's disease. In conclusion, primary HHV8 infection transmitted from a seropositive donor to a seronegative liver transplant recipient can cause a severe nonmalignant illness associated with high mortality. Donor screening for HHV8 should be considered in geographic areas with a high prevalence of such infection.

Impact of thrombocytopenia on survival of baboons with genetically modified pig liver transplants: clinical relevance.

A lack of deceased human donor livers leads to a significant mortality in patients with acute-on-chronic or acute (fulminant) liver failure or with primary nonfunction of an allograft. Genetically engineered pigs could provide livers that might bridge the patient to allotransplantation. Orthotopic liver transplantation in baboons using livers from alpha1,3-galactosyltransferase gene-knockout (GTKO) pigs (n = 2) or from GTKO pigs transgenic for CD46 (n = 8) were carried out with a clinically acceptable immunosuppressive regimen. Six of 10 baboons survived for 4-7 days. In all cases, liver function was adequate, as evidenced by tests of detoxification, protein synthesis, complement activity and coagulation parameters. The major problem that prevented more prolonged survival beyond 7 days was a profound thrombocytopenia that developed within 1 h after reperfusion, ultimately resulting in spontaneous hemorrhage at various sites. We postulate that this is associated with the expression of tissue factor on platelets after contact with pig endothelium, resulting in platelet and platelet-peripheral blood mononuclear cell(s) aggregation and deposition of aggregates in the liver graft, though we were unable to confirm this conclusively. If this problem can be resolved, we would anticipate that a pig liver could provide a period during which a patient in liver failure could be successfully bridged to allotransplantation.

Successful lung transplantation in an HIV- and HBV-positive patient with cystic fibrosis.

Prior to the advent of highly active antiretroviral therapy (HAART), HIV-infected patients were usually not considered as transplant candidates because of the poor prognosis of their underlying disease and concerns regarding the potential detrimental effects of immunosuppression on viral load and immune status. However, with the significant HAART-associated improvements in morbidity and mortality, good short-term outcomes after liver and kidney transplantation for patients with HIV infection have been reported. Nevertheless, HIV infection is currently considered a contraindication to lung transplantation in most transplant centers worldwide. The results of a double lung transplant performed in an HIV and HBV co-infected patient with cystic fibrosis (CF) and end-stage respiratory failure (ESRF) are presented after a 2-year follow-up. Approval of and recommendations for the management of this patient were obtained from the Italian National Center for Transplantation as an extension of the ongoing Italian protocol for liver and kidney transplantation in HIV-infected individuals. The operation was successful and the patient recovered rapidly after surgery. A cautious infectious and immunosuppressive management allowed so far the avoidance of major infectious complications and rejection. To the best of our knowledge, this is the first report of lung transplantation in an HIV and HBV co-infected patient.

Clinical burden of screening asymptomatic patients for coronary artery disease prior to liver transplantation.

The aim of this study is to assess the clinical burden of silent coronary artery disease (CAD) in cirrhotic candidates for liver transplantation (LT), and to evaluate the usefulness of a CAD screening approach. Between July 1999 and January 2006, we evaluated 627 LT candidates. All of them underwent a detailed clinical history. Sixteen had a previous diagnosis of CAD or symptoms suggestive (2.5%). The remaining 611 underwent further tests according to a predefined protocol, including EKG, echocardiogram and, on the basis of CAD risk factors, heart stress tests. Selective coronary angiography (SCA) was performed in the 30 patients with positive heart stress test: in only 2 did SCA show any CAD, and in both it was subcritical disease requiring neither intervention nor contraindicating LT. The 611 screened patients continued their follow-up until study closure or death. No coronary events occurred in the study population in a mean follow-up of 32.50 months (+/- 23.67 DS). No perioperative mortality related to CAD occurred in the 233 transplanted patients. In conclusion, no prognostic advantage was achieved by following a strict CAD screening protocol, leading us to believe that the cost-effectiveness of a similar screening can be unacceptably high in our setting.

Aetiology of cirrhosis of the liver has an impact on survival predicted by the Model of End-stage Liver Disease score.

BACKGROUND: Originally, aetiology of liver disease has been incorporated into the computation of the Model of End-stage Liver Disease (MELD) score. Clinical observations prompted us to hypothesize that patients with viral and alcoholic cirrhosis may differ in predicted survival rates. Until now, no large representative studies evaluated the impact of aetiology on long-term survival predicted by the Child-Pugh and MELD scores. MATERIALS AND METHODS: Four hundred and ninety-three patients who underwent transjugular intrahepatic portosystemic shunt implantation in Vienna, Austria, and Palermo, Italy, were included in this retrospective study. The main analyses were a logistic regression model and a Cox proportional hazards regression model calculating the interaction of the aetiology with the scores. RESULTS: Both groups had similar survival rates (median 1377 and 1721 days for viral and alcoholic cirrhosis, respectively; P = 0.58), but patients with viral cirrhosis had significantly lower MELD scores (P = 0.002). In the Cox analysis, aetiology had a significant impact on the prediction of overall survival by MELD score. For 3-month survival, MELD score was adequately predictive for both groups. For 1-year survival, aetiology had a significant impact on survival, indicating that patients with identical scores but different aetiologies differed in survival rates. When stratifying patients into high- and low-risk patients (MELD < 16 vs. MELD >or= 16), aetiology of cirrhosis had no impact on the predictive value for low-risk patients; high-risk-patients (MELD >or= 16) with viral cirrhosis had significantly lower survival rates than patients with alcoholic cirrhosis and identical scores. With regard to Child-Pugh Score, no significant differences between the two patient groups and in the prediction of 3-month and 1-year survival could be observed. CONCLUSIONS: Our study suggests that aetiology of cirrhosis has an impact on 1-year survival predicted by the MELD score. This becomes more apparent in patients with advanced stage of liver disease (MELD >or= 16). Since MELD score is used for ranking patients for liver transplantation and waiting times are regularly longer than 3 months, our observations suggest that with increasing time on the waiting list and severity of disease, patients with viral cirrhosis may have a disadvantage in the current allocation policy.

The recipient with portal thrombosis and/or previous surgery.

INTRODUCTION: Portal vein thrombosis (PVT) has been considered to be an absolute contraindication to liver transplantation (OLT) and previous upper abdominal surgery was considered to render it a high-risk procedure. Currently, these are only conditions considered risk factors increasing recipient morbidity and mortality. The objective of this study was to compare OLT perioperative morbidity, mortality, blood product consumption, and length of hospital stay among patients with or without PVT or with or without previous surgery. MATERIALS AND METHODS: Among 366 OLTs performed between July 1999 and November 2007, 33 liver transplant recipients displayed previous PVT while 34 had undergone previous surgery. The two groups of marginal recipients were compared with a cohort of 33 patients without PVT or previous surgery. RESULTS: The groups were homogeneous in terms of epidemiological variables, surgical techniques, and donor-related variables. In the PVT group, all analyzed parameters were the same as the control group; surgical time, anhepatic phase duration, early surgical complication, intensive care unit and hospital length of stay, and overall mortality. The only significant difference was the incidence of portal rethrombosis (P < .035). Among the previous surgery group, we did not observe significant differences. CONCLUSIONS: PVT and previous surgery should no longer be considered contraindications for OLT.

The role of basiliximab induction therapy in adult-to-adult living-related transplantation and deceased donor liver transplantation: a comparative retrospective analysis of a single-center series.

AIM: The aim of this study was to report our single-center experience with the use of basiliximab, in combination with a steroid and tacrolimus-based regimen in adult to adult living-related liver transplantation (ALRLT) and in deceased donor liver transplantation (DDLT). MATERIALS AND METHODS: Seventy-seven consecutive ALRLT recipients (group 1) and 244 DDLT recipients (group 2) were analyzed. All patients received 2 20-mg doses of basiliximab (days 0 and 4 after transplantation) followed by tacrolimus (0.15 mg/kg/d; 10-15 ng/mL target trough levels) and a dose regimen of steroids. Follow-up ranged from 4-1972 days after transplantation in group 1 and from 1-2741 days in group. RESULTS: In group 1, 89.32% of the patients remained rejection-free during follow-up, with an actuarial rejection-free probability of 93.51% within 3 months. Actuarial patient survival rate at 3 years was 84.49%. In group 2, 86.07% of the patients remained rejection-free during follow-up, with an actuarial rejection-free probability of 93.04% within 3 months. Actuarial patient survival rate at 3 years was 87.69%. We observed 14 cases of hepatitis C virus (HCV) recurrence in group 1 (prevalence of 26.92%) and 80 cases in group 2 (prevalence of 54.05%). CONCLUSION: Basiliximab in association with tacrolimus and steroids is effective in reducing episodes of acute cellular rejection (ACR) and increasing ACR-free survival after ALRLT and DDLT. No difference in patient and graft survival was found between group 1 and 2, nor was there any difference in the incidence of ACR between the 2 groups. However, less risk of HCV recurrence was present in the LRLT group.

Liver transplantation using donors older than 80 years: a single-center experience.

AIM: The shortage of organs for orthotopic liver transplantation (OLT) has forced transplantation centers to expand the donor pool by using donors traditionally labeled as "extended criteria donors." One such example is OLT using a donor with advanced age. MATERIALS AND METHODS: We retrospectively evaluated 10 patients who received a liver graft from cadaveric donors older than 80 years. We analyzed pretransplantation donor and recipient characteristics, as well as the evolution of the recipients. RESULTS: All 10 donors were older than 80 years (median age, 83.5; range, 80-93). No steatosis (>30%) was accepted in the older donor group. Medium follow-up was 19.5 months. The most frequent cause for OLT was hepatitis C virus (HCV) cirrhosis (8/10 patients). We had 1 case of primary nonfunction, 1 patient died immediately after surgery because of extrahepatic complications (cardiac arrest), and 2 other patients had a severe HCV recurrence and died after 1 and 2 years from OLT, respectively. Five patients had HCV recurrence and biliary complications were present in 60% of the patients. No cases of acute or chronic rejection were described. Overall survival rates after 1 and 3 years were 80% and 40%, respectively. CONCLUSIONS: Old donor age is not an absolute contraindication to OLT. Liver grafts from donors older than 80 years can be used knowing that there is a high risk of postoperative complications. Furthermore, the increased risk of developing severe HCV recurrence, related to older donor age, suggests that such livers should be used in HCV-negative recipients.

Adult to adult living-related liver transplant: report on an initial experience in Italy.

INTRODUCTION: Living-related liver transplantation has become the treatment of choice for many liver diseases. We present our initial analysis of 53 cases of adult to adult living-related liver transplantation performed in a single institute in Italy. MATERIALS AND METHODS: From January 2002 to September 2006, we performed 53 adult to adult living-related liver transplantations. The donors (age 18-53) all had genetic or emotional relationships; they were all ABO identical or compatible. Recipients (ages 18-68) suffered from cirrhosis secondary to viral etiology (18), hepatocellular carcinoma with viral cirrhosis (24), cystic fibrosis (2), primary biliary cirrhosis (2), hepatocellular carcinoma with non-viral cirrhosis (2), alcoholic cirrhosis (1), ornithine transcarbamylase deficiency (OTC), (1) criptogenic cryptogenic cirrhosis, (1) primary sclerosing cholangitis, (1) biliary atresia and metastatic carcinoid (1). Donor liver resection resulted in 51 right hepatectomies and two left hepatectomies. Graft body weight ratio was always above 0.8%; graft implantation was performed with the piggy back technique and, in 43 cases, with the use of veno-venous bypass. RESULTS: There was neither donor mortality nor need of blood transfusion. Actuarial recipient survival rate at 3 years was 82.66% and graft survival rate was 75.34%. Six patients underwent retransplantation: in four cases due to hepatic artery thrombosis, and in two, due to graft dysfunction. Three patients had one episode each of acute cellular rejection. CONCLUSION: Adult to adult living-related liver transplantation represents a resource to be used in confronting organ shortage, and is a valuable option for decreasing mortality and drop out from the waiting list.

Efficacy of interventional radiology procedures for the treatment of early ureteral complications after kidney transplantation.

UNLABELLED: Ureteral stricture and ureteral leakage are the most common early urological complications after kidney transplantation causing decreased urine output and increased serum creatinine and blood urea nitrogen. We report our experience with internal-external ureteral stent placement and ureteroplasty. MATERIALS AND METHODS: From August 1999 to January 2005, we treated nine patients presenting with stricture or leak. After an anterograde pyelogram, an internal-external nephrostomy catheter was inserted in all patients; in four patients we also performed ureteroplasty. RESULTS: The stricture and leak appeared from 12 to 93 days after kidney transplantation (mean = 39 +/- 29 days). After a mean of 80 +/- 43 days (range 25-141 days), the stent was successfully removed in seven patients (77%); no patient had a recurrence. The success was confirmed by a decline in serum creatinine (from 3.7 +/- 1.4 to 1.6 +/- 0.7 mg/dL) and blood urea nitrogen (from 54 +/- 24 to 28 +/- 7 mg/dL) with resolution of hydronephrosis on sonography. No procedure-related complications were observed. Surgical correction was necessary in two patients due to the persistence of a stricture. At long-term follow-up (50 +/- 17 months), seven kidneys were still functioning and two had failed due to chronic rejection. CONCLUSION: Nephrostomy catheter placement and ureteroplasty are safe, effective alternatives to surgery to treat early ureteral complications after kidney transplantation. Interventional radiology procedures reducing the morbidity and the likelihood of loss of graft function may improve graft and patient survival.

In situ split liver transplantation for adult and pediatric recipients: an answer to organ shortage.

BACKGROUND: We report our initial experience with in situ split liver transplantation (SLT) for adult and pediatric patients. PATIENTS AND METHODS: From June 2003 to August 2005, 177 liver transplantations in 165 patients, 133 adults (81%) and 32 children (19%), were performed at our institution. Over this period, 45 liver transplantations (25%) were performed with an in situ split liver technique in 44 patients: 17 (39%) were adults and 27 (61%) children. All of the adult split liver recipients were transplanted with an extended right graft (ERG; segments I + IV-VIII), while pediatric recipients received in 23 cases a left lateral segment (LLS; segments II-III) and in 4 cases an ERG from a pediatric donor. The 45 split liver grafts (21 ERGs and 24 LLSs) were generated from 35 donors. In 10 cases we used both grafts generated with an in situ split procedure to transplant our patients, while in 25 cases the procurement procedure was performed in collaboration with other transplant centers. RESULTS: After a median follow-up of 9 months (range, 1-27 months), the overall patient survival rate was 88% for adult patients and 82% for pediatric patients. Graft survivals were 88% and 79%, respectively. Two adult patients (12%) died from sepsis in the early postoperative period. Five children (18%) died after their transplantations. Only one pediatric recipient (2%) of primary SLT underwent retransplantation. Vascular complications were absent in adult recipients, whereas 4 arterial (14%) and 4 venous (14%) complications developed in the pediatric population. The incidence of biliary complications was 23% in adult and 18% in pediatric recipients. CONCLUSIONS: The use of in situ SLT for adult and pediatric populations allowed us to expand the cadaveric donor pool, significantly eliminating pediatric waiting list mortality without penalizing the adult population.

Corticosteroid-free immunosuppression in pediatric liver transplantation: safety and efficacy after a short-term follow-up.

BACKGROUND: We report our results with the use of corticosteroid-free immunosuppression after pediatric liver transplantation, evaluating the efficiency and safety of this protocol in the early posttransplantation period. PATIENTS AND METHODS: From July 2003 to October 2005, 34 liver transplantations were performed in 32 pediatric patients (19 boys, 13 girls) at our institution. Recipient median age was 5 years (range, 0.2-14 years), and median body weight was 10 kg (range, 4-49 kg). Twenty-seven patients received a graft from in situ split liver transplantation, 5 a whole graft. Twenty-nine children (90%) received an immunosuppressive therapy based on methylprednisolone IV bolus at reperfusion (10 mg/kg) plus tacrolimus given at an initial dose of 0.08 mg/kg/d and then adjusted to obtain whole blood trough levels of 10 to 15 ng/mL during the first 3 months and 5 to 10 ng/mL after the 3rd month; basiliximab was given on postoperative days 0 and 4. Biopsy-proven acute rejection episodes were treated by methylprednisone IV boluses. RESULTS: After a median follow-up of 9 months (range, 1-27 months), the overall patient survival rate was 84% and graft survival rate was 79%. Three children (9%) died after their transplantations. Three (9%) experienced episodes of biopsy-proven acute rejection, always treated with IV steroid boluses. Mean RAI score was 4. One patient experienced PTLD that resolved with temporary reduction of immunosuppression. Cytomegalovirus infection rate was 14%. Sepsis occurred in 2 cases (6%). CONCLUSIONS: Initial results with a steroid-free immunosuppressive protocol are encouraging, with low rates of acute rejection and infectious complications as in steroid-based protocols.

A safe immunosuppressive protocol in adult-to-adult living related liver transplantation.

BACKGROUND: In this series of 32 adult-to-adult living related liver transplantations, we assessed the efficacy and safety of basiliximab in combination with a tacrolimus-based regimen. Basiliximab, a chimeric monoclonal antibody directed against the alpha chain of the interleukin-2 (IL-2) receptor (CD25), has been extensively evaluated as induction therapy for cadaveric liver transplant recipients. PATIENTS AND METHODS: Thirty-two adult-to-adult living related liver transplantations were performed in the last 3 years. All patients received two 20 mg doses of basiliximab (days 0 and 4 posttransplantation) followed by tacrolimus (0.15 mg/kg/d; 10-15 ng/mL target trough levels) and steroids (starting with 20 mg IV switched to PO as soon as the patient was able to eat and weaned within 1-2 months). The average follow-up was 395 days after transplantation. RESULTS: Of the patients, 93.75% remained rejection-free during follow-up with an actuarial rejection-free probability of 92.59% within 3 months. Two patients (6%) had one episode of biopsy-proven acute cellular rejection (ACR). Actuarial patient and graft survival rates at 3 years were 86.85% and 81.25%. One patient (3%) experienced one episode of sepsis. There was no evidence of cytomegalovirus infections or side effects related to the basiliximab. We found zero de novo malignancy but we observed two patients with metastatic spread of their primary malignancy during the follow-up. CONCLUSION: Basiliximab in association with tacrolimus and steroids is effective as prophylaxis of ACR among adult living related liver transplant recipients.

Practice of adult liver transplantation in Italy. Recommendations of the Italian Association for the Study of the Liver (A.I.S.F.).

Liver transplantation is an efficient procedure as performed in Italy, yet major differences are present in terms of practice. In an effort to facilitate an homogeneous practice of liver transplantation in Italy, the Italian Association for the Study of Liver Disease has instituted a Commission aimed at providing recommendations on non-urgent liver transplantation in adults, based on current evidence. This nation-wide commission which included experienced hepatologists, surgeons and pathologists with major interest in liver transplantation has drafted a final document in October 2004, approved by the Italian Association for the Study of Liver Governing Board, whose key arguments and main conclusions are summarised in the present paper. The Commission has made specific recommendations on the following topics: the current needs of liver transplantation in Italy; the indications to liver transplantation and re-liver transplantation, with special reference to controversial issues and the minimal listing criteria; the use of marginal donors and the need to optimise donor/recipient matching; the use of living donor liver transplantation; the management of the waiting list and the introduction of Model for End-Stage Liver Disease to define priorities; the clinical management of liver transplantation recipients and disease recurrence; the implementation of audits and outcome monitoring; the training of transplant surgeons and hepatologists and the requirements for Centre accreditation; the pathology of liver transplantation.