Showing papers in "Clinical Transplantation in 2006"

Infectious complications after kidney transplantation: current epidemiology and associated risk factors.

Abstract: Background: The impact of newer immunosuppressive and antimicrobial prophylactic agents on the pattern of infectious complications following kidney transplantation has not been well studied. Methods: This is an observational study in 127 adult recipients transplanted from 2001 to 2004. Patients received thymoglobulin (ATG) (50%) or basiliximab (50%) for induction and were maintained on mycophenolate mofetil, either tacrolimus (73%) or sirolimus (SRL) (27%), and prednisone (79%). Antimicrobial prophylaxis included perioperative cefazolin, trimethoprim/sulfamethaxazole for six months, valganciclovir for three months and nystatin for two months. Regression models were used to examine the association of various factors with infections. Results: We observed 127 infections in 65 patients, consisting of urinary tract infection (UTI) (47%), viral infections (17%), pneumonia (8%) and surgical wound infections (7%). UTI was the most common infection in all post-transplant periods. Enterococcus spp. (33%) and Escherichia coli (21%) were the most prevalent uropathogens. Of six patients with cytomegalovirus infection, none had tissue-invasive disease. There were no cases of pneumocystis pneumonia or BK nephropathy. Six patients developed fungal infections. Two deaths due to disseminated Rhizopus and Candida albicans accounted for a 1.5% infection-related mortality. Retransplantation and ureteral stents were independently associated with UTI (OR = 4.5 and 2.9, p = 0.06 and 0.03, respectively), as were ATG and SRL with bacterial infections (OR = 3.3 and 2.5, p = 0.009 and 0.047, respectively). Conclusion: This study suggests that the use of newer immunosuppressive agents in recent years is associated with some changes in the epidemiology of post-transplant infections. Enterococci have become the predominant uropathogen. Invasive fungal infections, although rare, are often fatal.

Wound complications following kidney and liver transplantation

Abstract: Advances in surgical techniques and immunosuppression (IS) have led to an appreciable reduction in postoperative complications following transplantation. However, wound complications as probably the most common type of post-transplantation surgical complication can still limit these improved outcomes and result in prolonged hospitalization, hospital readmission, and reoperation, consequently increasing overall transplant cost. Our aim was to review the literature to delineate the evidence-based risk factors for wound complications following kidney and liver transplantation (KTx, LTx), and to present the preventive and therapeutic modalities for this bothersome morbidity. Generally, wound complications are categorized as superficial and deep wound dehiscences, perigraft fluid collections and seroma, superficial and deep wound infections, cellulitis, lymphocele and wound drainage. The results of several studies showed that the most important risk factors for wound complications are IS and obesity. Additionally, there are surgical and/or technical factors, including type of incision, reoperation, and surgeon's expertise, as well as comorbidities such as advanced age, diabetes mellitus, malnutrition, and uremia. Preventive management of wound complications necessitates defining their etiological factors so that their detrimental effects on healing processes can be addressed and reduced. IS modalities and agents, especially sirolimus (SRL), and steroids (ST) should be adjusted according to the patient's co-existing risk factors. SRL should be administered three months after transplantation and ST should be tapered as soon as possible. A body mass index (BMI) lower than 30 kg/m2 is advisable for inclusion in a transplantation program, but higher BMIs do not exclude recipients. Surgical risk factors can be prevented by applying precise surgical techniques. Therapeutic modalities must focus on the most efficient and cost-effective medications and/or interventions to facilitate and improve wound healing.

Supporting medication adherence in renal transplantation (SMART): a pilot RCT to improve adherence to immunosuppressive regimens.

Abstract: Background Although non-adherence to an immunosuppressive regimen (NAH) is a major risk factor for poor outcome after renal transplantation (RTx), very few studies have examined non-adherence intervention in this context. This pilot randomized controlled trial (RCT) tested the efficacy of an educational-behavioural intervention to increase adherence in non-adherent RTx patients. We also assessed how NAH evolves over time. Methods Eighteen RTx non-adherent patients (age: 45.6 +/- 1.2 yr; 78.6% male) were randomly assigned to either an intervention group (IG) (n = 6) or an enhanced usual care group (EUCG) (n = 12), the latter receiving the usual clinical care. The IG received one home visit and three telephone interviews. We assessed NAH through electronic monitoring (EM) of medication intake during a nine-month period (three months intervention, six months follow-up). Results Five of 18 patients withdrew. Inclusion in the study resulted in a remarkable decrease in NAH in both groups over the first three months (IG chi(2) = 3.97, df = 1, p = 0.04; EUCG chi(2) = 3.40, df = 1, p = 0.06). The IG showed the greatest decrease in NAH after three months, although this did not reach statistical significance (at 90 d, chi(2) = 1.05, df = 1, p = 0.31). Thereafter, NAH increased gradually in both groups, reaching comparable levels at the end of the six-month follow-up (i.e. at nine months). Conclusion Our findings suggest an inclusion effect. Although the intervention in this pilot RCT appeared to add further benefit in medication compliance, a lack of statistical power prevented us from making a strong statistical statement.

Surgical strategies for liver transplantation in the case of portal vein thrombosis--current role of cavoportal hemitransposition and renoportal anastomosis.

Abstract: Portal vein thrombosis (PVT), a common complication of end stage liver disease, is no longer considered a definite contraindication for liver transplantation (LTx). The clinical decision to perform an LTx in the case of PVT depends on the degree of PVT and the experience of the surgeon. Eversion thromboendovenectomy was suggested by most authors as the surgical technique of choice for PVT grade 1, 2, and 3. If PVT obstructs more extended parts of the porto-mesenteric venous circulation, surgical options would include different types of venous jump graft reconstructions or arterialization of the portal vein. Combined liver and small bowel transplantation is another possible alternative. Cavoportal hemitransposition (CPHT) and renoportal anastomosis (RPA) were recently particularly advocated as creative surgical strategies in case of diffuse PVT. In this work, we focus on CPHT and RPA surgical techniques during LTx, which attempts to secure the portal flow to the liver graft in case of pre-existent diffuse PVT. We provide a review of all reported clinical experience at international clinical centers using these techniques. According to our meta-analysis a total of 15 studies were published on this topic between 1996 and 2005. In summary, a total of 56 orthotopic LTx have been performed in 53 patients (28 men, 25 women) combined with either CPHT or RPA, for the purpose of providing the donor graft with adequate inflow. Mean age was 44 yr including two patients who were infants, with the youngest recipient being two yr old. Main indications for LTx were liver cirrhosis caused by viral hepatitis, alcoholic cirrhosis and cryptogenic cirrhosis. CPHT was performed in 46 cases, and RPA in 10 cases. Thirty-five of 53 patients (66%) had surgery previous to LTx. Of these, 13 patients (37%) [corrected] presented with a history of other previous surgical procedures for decompression of portal hypertension or treatment of associated complications (portocaval shunts, splenectomy, etc). Ascites, renal dysfunction, lower extremity and torso edema and variceal bleeding were dominant post-operative complications after CPHT or RPA noted in 22 cases (41.5%), 18 cases (34%), 17 cases (32%) and 13 cases (24.5%) respectively. Patients' follow-up ranged from two to 48 months. Thirty nine of 53 patients [corrected] (74%) survived [corrected] and 14 patients died (26%) [corrected] during the course of observation. Based on the literature, we conclude that the ideal technique to overcome PVT during LTx is still controversial. Short-term follow-up results of both methods are promising, however, long-term results are unknown at present. Furthermore, clinical follow-up and basic experimental work is required to evaluate the influence of systemic venous inflow to the liver graft with respect to long-term liver function and liver regeneration.

A systematic review of barriers in access to renal transplantation among African Americans in the United States.

Abstract: Background: African-American patients with end-stage renal disease are less likely than white patients to undergo renal transplantation. The development of strategies to address this disparity requires an evidence-based understanding of the barriers that impede access to renal transplantation among African Americans in the United States. Methods: In September 2005, we searched MEDLINE, EMBASE, and CENTRAL for articles that identified the barriers that impeded African Americans’ access to renal transplantation. Two reviewers independently extracted relevant data from the included studies. Barriers were broadly divided under two categories: (i) patient-related barriers; and (ii) healthcare-related barriers. Results: We obtained 76 potentially relevant articles of which 11 studies were included in the final review. Several patient-related barriers – personal and cultural beliefs about transplantation, lower socioeconomic status and levels of education, and healthcare-related barriers – physician perception about survival of African Americans post-transplantation, inadequate transplant work-up despite being referred, and HLA-mismatching were identified at different stages of the transplantation process. Personal and cultural beliefs of African-American patients were consistently identified as patient-related barriers among several studies. Physicians’ perception about post-transplantation survival of African Americans was the most commonly identified healthcare-related barrier. Conclusions: A wide spectrum of patient-related barriers including their personal and cultural beliefs about transplantation and several healthcare-related barriers at different stages of the transplant process impedes access to renal transplantation among African Americans in the United States. A multisectoral approach focusing on these barriers needs to be evaluated to reduce disparities in renal transplantation in the United States.

Donor polymorphisms in Toll-like receptor-4 influence the development of rejection after renal transplantation

Abstract: a Medicine, b Surgery, c Abstract: Background: Although innate immunity is crucial to host defense against pathogens, the extent to which innate immune mechanisms participate in the rejection of allogenic tissues in humans is unknown. We hypothesize that activation of innate immunity through Toll-like receptors (TLRs) critically regulates the development of renal allograft rejection. We have recently demonstrated decreased acute rejection in lung transplant recipients heterozygous for either of two functional polymorphisms in TLR4 associated with endotoxin hyporesponsiveness. In the present investigation, we sought to evaluate the role of innate immune activation through TLR4, in either donor or recipient, upon the development of renal allograft rejection. Methods: Patients and donors were screened for the TLR4 functional polymorphisms (Asp299Gly and Thr399Ile) by polymerase chain reaction (PCR) using sequence-specific primers. Results: The incidence of biopsy-proven acute renal allograft rejection was significantly reduced in patients receiving donor grafts heterozygous for the Asp299Gly or Thr399Ile alleles, when compared with wild type (22% vs. 0%, respectively, p 5 0.02). There was no association with recipient TLR4 allele and rejection. Conclusions: The results suggest activation of innate immunity through TLR4 in the donor kidney contributes to the development of acute rejection after renal transplantation.

Quality of life after organ transplantation in type 1 diabetics with end-stage renal disease.

Abstract: UNLABELLED: Quality of life (QOL) should be an important consideration while choosing therapeutic options for patients with type 1 diabetes mellitus (DM) and end-stage renal disease (ESRD) including dialysis, cadaver (CKT) or living kidney transplant (LKT) or simultaneous pancreas-kidney (SPK) transplant. METHODS: QOL was assessed in four groups of patients with history of type 1 DM and ESRD: recipients of SPK (n = 43), CKT (n = 43), LKT (n = 11) and wait listed (WL) patients (n = 23). Diabetes Quality of Life (DQOL), Short Form-36 (SF-36) and Quality of Well-Being (QWB) questionnaires were utilized. A subset of SPK (n = 19) and CKT (n = 12) recipients underwent longitudinal QOL evaluation. RESULTS: On DQOL questionnaire, SPK group had better satisfaction subscore compared with CKT (1.8 +/- 0.5 vs. 2.2 +/- 0.6, p < 0.01) LKT (1.8 +/- 0.5 vs. 2.4 +/- 0.7, p < 0.05) and WL (1.8 +/- 0.5 vs. 2.6 +/- 0.6, p < 0.001) groups and better impact subscore compared with CKT (1.7 +/- 0.6 vs. 2.1 +/- 0.6, p < 0.05) and WL (1.7 +/- 0.6 vs. 2.3 +/- 0.6, p < 0.01) groups. There were no significant differences on physical/mental composite scores of SF-36. QWB score was better in SPK group vs. WL group (0.62 +/- 0.11 vs. 0.55 +/- 0.04, p < 0.05). Longitudinal decline in satisfaction (2.3 +/- 0.5 vs. 2.6 +/- 0.9, p = 0.058) and impact (2.0 +/- 0.5 vs. 2.2 +/- 0.5, p = 0.019) subscores of DQOL were noted in CKT group. There were no significant changes in the composite scores of SF-36 in both groups. QWB scores declined in the CKT group (0.67 +/- 0.10 vs. 0.61 +/- 0.05, p = 0.01). CONCLUSION: QOL was better in type 1 diabetics with ESRD following transplantation when compared with remaining on WL. SPK transplantation had significant positive effect on diabetes-related QOL which was sustained longitudinally but it was difficult to show an overall improvement in general QOL.

Long-term follow-up after recurrence of primary biliary cirrhosis after liver transplantation in 100 patients.

Abstract: Orthotopic liver transplantation (OLT) is the only effective curative therapy for end-stage primary biliary cirrhosis (PBC). Survival after OLT is excellent, although recent data have shown a recurrence rate of PBC of up to 32% after transplantation. The aim of this study is to investigate the course after disease recurrence, particularly with regard to liver function and survival in a long-term follow-up. Between April 1989 and April 2003, 1,553 liver transplantations were performed in 1,415 patients at the Charite, Virchow Clinic. Protocol liver biopsies were taken after one, three, five, seven, 10 and 13 yr. One hundred (7%) patients suffered from histologically proven PBC. Primary immunosuppression consisted of cyclosporine (n = 54) or tacrolimus (Tac) (n = 46). Immediately after OLT, all patients received ursodeoxycholic acid. Corticosteroids were withdrawn three to six months after OLT. The median age of the 85 women and 15 men was 55 yr (range 25-66 yr). The median follow-up after liver transplantation was 118 months (range 16-187 months) and after recurrence 30 months (range 4-79 months). Actuarial patient survival after five, 10 and 15 yr was 87, 84 and 82% respectively. Ten patients (10%) died after a median survival time of 32 months. Two of these patients developed organ dysfunction owing to recurrence of PBC. Histological recurrence was found in 14 patients (14%) after a median time of 61 months (range 36-122 months). Patients with Tac immunosuppression developed PBC recurrence more often (p < 0.05) and also earlier (p < 0.05). Fifty-seven patients developed an acute rejection and two patients a chronic rejection episode. Liver function did not alter within the first five yr after histologically proven PBC recurrence. Multivariate analysis of the investigated patients showed that the recipient's age and Tac immunosuppression were significant risk factors for PBC recurrence. Long-term follow-up of up to 15 yr after liver transplantation, owing to PBC, in addition to maintenance of liver function, shows excellent organ and patient survival rates. Although protocol liver biopsies revealed histological recurrence in 14 (14%) patients, only two patients developed graft dysfunction. Tac-treated patients showed more frequently and also earlier histologically proven PBC recurrence; however, in our population we could not observe an impact on graft dysfunction and patient's survival.

FTY720 (fingolimod) in renal transplantation.

Abstract: FTY720 (Fingolimod) is a novel immunomodulator with a mode of action that is completely different from classical immunosuppressants. FTY is a structural and functional analogue of the natural serum lipid, sphingosine, and is the first in a new class of drugs called sphingosine 1-phosphate receptor (S1P-R) modulators. This review discusses the recent findings on the mechanism of action, preclinical models and outlines the results of the ongoing clinical development program. FTY is highly effective in prolonging allograft survival in preclinical models of transplantation and in experimental models of autoimmune diseases. In clinical trials, this novel compound was investigated in de novo renal transplantation and in multiple sclerosis. Pharmacokinetics are characterized by a prolonged absorption phase, a large volume of distribution, and a long elimination half-life. FTY induces a rapid and transient decrease in lymphocyte counts, which supports the modulatory effects of the drug on lymphocyte sequestration. The most common adverse event was asymptomatic transient bradycardia, a pharmacodynamic effect modulated by atrial S1 P-R. FTY failed to show an improvement in efficacy for the prevention of renal allograft rejection in two large phase III studies. FTY treatment regimens were associated with impaired renal function and the development of macula edema. Consequently, the further development in renal transplantation was stopped. Because initial clinical studies strongly suggest that FTY is highly effective in multiple sclerosis FTY is now being explored in phase III studies for the treatment of demyelinating diseases, Ongoing studies in multiple sclerosis are eagerly awaited because they may provide novel therapeutic options for patients with autoimmune diseases.

Antifibrotic actions of mycophenolic acid

Abstract: Mycophenolic acid (MPA) is a highly selective, non-competitive and reversible inhibitor of the inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme in the de novo biosynthesis of guanosine nucleotides. Mycophenolate mofetil (MMF, the ester prodrug of MPA) strongly inhibits both T- and B-lymphocyte proliferation and has now been widely used in the prevention of acute and chronic allograft rejection. Recent evidence, however, suggests that MMF is also capable of inhibiting the proliferation of non-immune cells. In various cell lines, e.g. smooth muscle cells, renal tubular cells, mesangial cells, and fibroblasts, MPA reduced or even abrogated proliferation in response to proliferative stimuli. In animal studies, MMF ameliorated renal lesions in immune-mediated disease, e.g. in the Anti-Thy 1.1 model and experimental lupus nephritis, but was also effective in non-immune-mediated renal damage, e.g. in the rat remnant kidney model or in a model of chronic cyclosporine nephrotoxicity in the rat. In humans, MMF reduced proteinuria in steroid-resistant nephrotic syndrome and had beneficial effects in the prevention and treatment of chronic allograft nephropathy and calcineurin inhibitor toxicity through the reduction of immune- and non-immune-mediated renal damage. MMF is well tolerated and has proven to be a relatively safe drug. Taken together, there is a growing body of evidence pointing to therapeutic applications of MMF other than immunosuppression, in particular the prevention of fibrosis.

Impact of stress, distress and feelings of indebtedness on adherence to immunosuppressants following kidney transplantation.

Abstract: In order to ensure transplantation's long-term success, transplant recipients need to comply with a strict regimen of immunosuppressant medication on a daily basis for the rest of their lives. Nonadherence is one of the major causes of organ rejection. Because compliance is voluntary, it is likely to be influenced by an individual's beliefs and feelings. This study examined the impact on compliance of the following factors: (1) transplant-related stress; (2) general perceived stress; (3) psychosocial distress and (4) feelings of indebtedness and guilt towards the donor. Fifty kidney recipients (34 men, 16 women) filled out self-report questionnaires. The results indicate that 46% acknowledged sub-optimal compliance in the last month; patients more often reported not taking the medication exactly as prescribed than forgetting to take it. The results also suggest that psychological distress and general perceived stress affect compliance negatively, whereas feelings of indebtedness improve it. These results have implications for the understanding and management of compliance following organ transplantation.

Hepatitis B prophylaxis post-liver transplant without maintenance hepatitis B immunoglobulin therapy.

Abstract: Background: We examined outcomes in recipients who underwent a liver transplant for HBV-induced liver disease and received a protocol for prophylaxis that did not use HBIG maintenance. Results: Between October 2002 and July 2005, a total of 14 liver transplant recipients were identified that met the study criteria. Mean recipient age was 47.6 yr; mean donor age was 37.2 yr. Category of transplant was as follows: cadaveric liver (n=10, 71%), cadaveric split-liver (n=2, 14%), and cadaveric liver–kidney (n=2, 14%). Liver disease was diagnosed at a mean of 7.3 yr before transplant; three (21%) had a coexisting hepatocellular cancer at the time of transplant. Pre-transplant, all 14 (100%) recipients were hepatitis B surface antigen (HBsAg) positive, and 11 (79%) were HBV DNA positive (mean viral load of 251.2 pg/mL). Three (21%) were E antigen positive, and one (7%) was D antigen positive. Pre-transplant, seven patients (50%) were on anti-viral therapy and there was documented diminution in viral loads after initiating anti-viral therapy in 3 cases. Three (21%) were hepatitis C virus (HCV) antigen positive and all had low-RNA titers. With mean follow-up of 14.1 months, all 14 patients are alive with a functioning graft. Mean ALT, AST and total bilirubin values are currently at 43.2, 32.2, and 0.84, respectively. One recipient remains HBsAg surface antigen positive post-transplant but has normal lab values. The remaining recipients have no evidence of HBV recurrence by serology and protocol biopsies. The regimen has been well tolerated without the need for drug reduction or discontinuation because of side-effects. Conclusion: Longer follow-up is needed, but this regimen may represent an alternative to chronic HBIG maintenance therapy.

UNOS Liver Registry: ten year survivals.

Abstract: 1. This is a retrospective study using the UNOS database to examine the effects of various recipient, donor and transplant factors on 10-year liver graft survivals. A total of 68,776 adult liver transplants were reported to OPTN/UNOS from September 1987 to July 2006. Recipient, donor and transplant characteristics were compared using the paired t test for continuous variables. The chi-square tests were used to compare categorical variables. We calculated actual liver graft survival rates using the Kaplan-Meier methods. For statistical comparisons of survival curves, we used log-rank analysis. 2. The number of recipients who were older than 65 years of age has been steadily increasing each year. Since 1998, more than 10% of all recipients were over 65 years old, and in 2003 it reached 15.3%. The 1-, 5- and 10-year graft survival rates of liver transplant recipients who were younger than 65 years were 82.1%, 67.8% and 52.6%, respectively; for recipients who were 65 years or older they were 77.5%, 59.7% and 41.2%, respectively. 3. The impact of recipient, donor and transplant factors on liver graft survivals changed over time after liver transplantation. Recipient age, sex, having diabetes or angina and being positive against HCV antibody had both short- and long- term effects on transplant grafts. Pre-transplant dialysis and cold ischemia time had only short-term effects. 4. Our results showed that the transplants from older donors, DCD donors, HCV antibody-positive donors and diabetic donors had poorer graft survival than the transplants from other types of donors. 5. When the grafts which failed within one year were excluded from analyses, recipients whose serum total bilirubin at transplantation was higher than 7 mg/dL or recipients who were on mechanical ventilation at transplantation had better liver graft survival compared to other recipients. The better prognosis among recipients with higher total bilirubin or recipients on mechanical ventilation is partially explained by younger recipient age in these recipient groups. 6. The present allocation policy, the MELD-based deceased donor liver allocation system, mainly assigns a donor to a recipient depending on recipient pre-transplant medical status. However, to optimize the use of limited organs, not only pre-transplant recipient status but also expected liver graft outcome based donor assignment to recipients should be incorporated. 7. In conclusion, our study on ten-year liver graft survival showed that impacts of recipient, donor and transplant factors on liver graft survivals changed over time after liver transplantation.

Are personnel in transplant hospitals in favor of cadaveric organ donation? Multivariate attitudinal study in a hospital with a solid organ transplant program

Abstract: Introduction: A considerable number of professionals who work in a hospital could be against organ donation, which means that when the time comes, they could act as an obstacle to donation. The objective of this study was to analyze the attitude of hospital professionals toward organ donation and to determine the factors that influence this attitude in a Spanish center with a transplant program. Materials and methods: The study was carried out in a third-level Spanish hospital with a solid organ transplant program. A random sample was taken (n = 1262) and stratified by job category and type of service. Attitude was evaluated using a validated questionnaire. Contact was made in each service with the person responsible for each of the job categories in order to distribute the survey. The survey was completed anonymously and was self-administered. Student's t-test, the chi-squared test, and logistic regression analysis were applied in the statistical analysis. Results: The survey completion rate was 93% (n = 1168). Most respondents were in favor of donation [69% (n = 808)]. Of those who are not in favor, 29% (n = 105) provide fear of apparent death as the reason whilst most do not give a reason (negative assertion; 57%; n = 206). There are many factors related to this attitude toward donation, which are evident in the multivariate analysis: (i) job category, in which physicians are twice as likely to be in favor of donation than ancillary personnel (OR = 2.02); (ii) a respondent's knowledge of brain death (OR = 1.64); (iii) having discussed the matter of organ donation and transplantation within the family (OR = 1.89); (iv) a preference for other options apart from burial (OR = 3.66); (v) being in favor of the performance of autopsy if it were necessary (OR = 2.76); (vi) not being concerned about mutilation of the cadaver (OR = 2); and (vii) having a partner with a favorable attitude toward donation (OR = 2.2). Conclusions: Attitude toward cadaveric organ donation among personnel in a transplant hospital is similar to that described in the general public and is determined by many factors. The following factors are most noteworthy: (i) job category; (ii) knowledge of the concept of brain death; (iii) consideration of the matter of donation in the family; and (iv) fear of manipulation of the cadaver. In view of this attitude, which is similar to that of the general public, it is necessary to carry out promotion activities if we want to increase cadaveric donation rates.

Management of the sensitized cardiac recipient: the use of plasmapheresis and intravenous immunoglobulin.

Abstract: Previously, we reported that the combination of plasmapheresis (PP) and intravenous immunoglobulin (IVIg) allow sensitized patients to undergo orthotopic heart transplantation (OHT), even across a positive crossmatch. In the current study, the effect of that combination, PP+IVIg, on survival of a larger group of such recipients is investigated. The latter group (I) consisted of 35 sensitized patients who received PP+IVIG together with standard immunosuppressive drugs. Rejection was seen in 11 patients, findings strongly suggestive of a vascular (humoral) being identified in five of those cases. Four deaths occurred, two of them in the immediate post-operative period, one after almost six months, and one after almost two yr post-OHT. Follow-up range 4.5 months to 7.8 yr post-OHT (average=1.1 yr). Patient survival was analyzed after generation of a Kaplan-Meier plot. Comparison with a control OHT group (II) given standard immunosuppressive drugs only (N=276) showed enhanced survival of group I (p=0.0414 by log-rank test). We conclude that the combination of PP and IVIG (i) is associated with declines in T- and B-percent-reactive antibody and in crossmatch positivity, and (ii) is very useful in the management of the sensitized cardiac patient undergoing OHT, often allowing a successful outcome to transplantation in the face of a positive crossmatch.

Biliary complications after liver transplantation.

Abstract: Biliary complications remain a substantial cause of morbidity following liver transplantation. They have been reported to occur in a rate of 10-15% of full-size transplantations and may be higher in living donor, split or reduced size liver transplantations. The most common biliary complications following liver transplantations are leaks and strictures. In both, the incidence varies with respect to type of graft and donor as well as the type of biliary anastomosis. The management of the biliary complications requires a multidisciplinary approach and has changed over the past decade, favoring endoscopic and radiological techniques. Surgical revision including retransplantation is reserved for patients in whom endoscopic and interventional modalities are unsuccessful.

Autologous hematopoietic stem cell transplantation for progressive multiple sclerosis: report of efficacy and safety at three yr of follow up in 21 patients.

Abstract: Objective: To observe the efficacy and toxicity of autologous hematopoietic stem cell transplantation (HSCT) in progressive multiple sclerosis (PMS). Methodology: Twenty-one patients with PMS were treated with autologous HSCT. Stem cells were mobilized with cyclophosphamide (CY) and granulocyte colony-stimulating factor. After conditioning regimen of CY and total body irradiation or BEAM, stem cells were reinfused. CD34+ cell selection of the graft was performed and anti-thymocyte globulin was given for T-cell depletion. The probabilities of confirmed progression-free survival and disease activity-free survival were used to assess the efficacy and the adverse experiences were recorded to detect the toxicities. Results: The median follow-up time was 42 (6–65) months. The probabilities of confirmed progression-free survival and the disease activity-free survival were 75% and 33.3%, respectively. The principal adverse events included allergy, infection, elevation of liver enzymes, transient neurologic deterioration and depression. Two patients died of severe pneumonia and varicella-zoster virus hepatitis, at 4.5 and 15 months post-transplant, respectively. Conclusions: Autologous HSCT seems beneficial to PMS. However, more patients and longer follow up would be required to assess the risk/benefit ratio.

Use of cytokine polymorphisms and Epstein-Barr virus viral load to predict development of post-transplant lymphoproliferative disorder in paediatric liver transplant recipients.

Abstract: Objective Currently there are no tests to accurately identify paediatric liver transplant patients at risk for post-transplant lymphoproliferative disorder (PTLD). Herein we describe the use of cytokine polymorphisms and real-time quantitative polymerase chain reaction (qPCR) Epstein-Barr virus (EBV) viral load to identify patients at risk for PTLD development. Methods Between 2001 and 2004, approximately 1047 patient samples were collected for qPCR for EBV in 59 patients. EBV viral load was reported in three groups: low EBV ( 4000 copies/microg DNA) and biopsy-proven PTLD. All 59 patients also had cytokine polymorphism genotyping performed for six cytokine polymorphisms (transforming growth factor (TGF)-beta, tumor necrosis factor (TNF)-alpha, interleukins (IL)-6, IL-10, IL-2, and interferon (IFN)-gamma) from DNA isolated from peripheral blood mononuclear cells. Positive predictive value (PPV) and negative predictive value (NPV) were calculated using qPCR and cytokine polymorphism results. Data are reported as a mean +/- standard error of the mean. Results There were 35 males and 24 females with a mean follow-up of 34.9 months. EBV viral load had a PPV and NPV of 29 and 95%, respectively. The low IFN-gamma (A/A) polymorphism was found to be present in 4/6 PTLD patients (67%) and only 17/53 (33%) non-PTLD patients. When the low A/A IFN-gamma polymorphism was combined with EBV viral load for prediction of PTLD, PPV and NPV were 57 and 93%, respectively. Discussion Use of cytokine genotyping in conjunction with qPCR for EBV viral load can significantly improve the predictive value of diagnostic tests for identification of patients at high risk for PTLD.

Long-term renal function after liver transplantation is related to calcineurin inhibitors blood levels.

Abstract: Renal dysfunction is common after liver transplantation (LT). The aim of our study was to assess the prevalence of renal dysfunction 5 yr after LT and to identify risk factors for the development of this complication.

Thirty year trend in kidney transplants: UCLA and UNOS Renal Transplant Registry.

Abstract: After the analysis of the UNOS Renal Transplant Registry database, with more than 138,000 cases, we showed that: 1. The important improvement seen in the last 20 years is basically only in the short-term graft survivals, with the best advances in the first 6 months after transplant. Unfortunately, the graft loss rate after the first year post-transplant remains the same as observed 10 years ago. The development of new immunosuppression has not been sufficient in avoiding chronic graft rejection. 2. Ten year graft survival has remained essentially the same in the period after 1996 as the reference period of 1987 to 1995. The year at which the transplant had been performed had absolutely no effect in the past 5. As to trends, there was an important shift to older recipients and older donors which has been notable in the 30 years. Living unrelated and spouse donors have increased 10 years on the long-term survival of HLA identical sibling donor, parental and cadaver donor grafts. 3. The factors which had a small effect before, and continued to have a similar small effect were: regrafts, high PRA, and sex of recipient. 4. The factors which had a large effect before and continued to influence long-term survival were: living versus cadaver donor, age of the recipient, age of the donor, original disease of the recipient, race of the recipient, immediate kidney function and delayed graft function. HLA matching had approximately a 15% difference in best and worst mismatches in the earlier and 10% in the later periods. 6. Cold ischemia time has relatively little effect on graft survival or percent of nonfunctional kidneys in all groups.

Attitude of kidney patients on the transplant waiting list toward related-living donation. A reason for the scarce development of living donation in Spain.

Abstract: Summary: Introduction: Most Spanish transplant centers have on-going living kidney transplant programs. However, such transplants are not increasing as a proportion of the total number of kidney transplants. The objective of this study is to analyze the attitude of kidney patients on the kidney transplant waiting list toward living kidney donation. Materials and methods: The patients studied were selected from those included on the kidney transplant waiting list from November 2003 until September 2005 (n = 221). Attitude toward living donation was evaluated using a psychosocial questionnaire. It was completed in a direct personal interview with an independent health-care worker from the Transplant Unit. Student's t-test and the chi-squared test were applied. Results: Two hundred and fourteen patients completed the questionnaire (97%), of which 35% would accept a related living kidney if it were offered to them, 60% would prefer to wait on the waiting list and the remaining 5% are undecided. Up to 66% (n = 134) of patients report that a member of their family or a friend have offered them an organ for donation. Eighty-nine percentage believe that there is some risk involved in living kidney donation, although it is not a factor that affects whether an organ would be accepted or not (p = 0.767). The psychosocial variables that affect attitude toward accepting a related living kidney are: (i) age: the youngest are those who are most likely to accept (40 vs. 45-yr-old; p = 0.010); (ii) descendents: patients without descendents are more likely to accept a living organ (56% vs. 27%; p < 0.000); (iii) marital status: a greater percentage of single respondents would be prepared to receive this type of transplant compared to the group of married respondents (55% vs. 30%. p = 0.007); and (iv) level of education: those with a higher level of education are more likely to accept a living organ (43% have secondary or university studies vs. 28% who only have primary education; p = 0.040). Conclusion: Patients on the waiting list for a kidney transplant do not have a very favorable attitude toward receiving a related-living donor organ, although members of their family have offered them one of their organs. The profile of a patient who would accept a related-living donated kidney is a young, single person, without descendents, and with a high level of education.

Limitation of the model for end-stage liver disease for outcome prediction in patients with cirrhosis-related complications.

Abstract: The model for end-stage liver disease (MELD) has been used to prioritize cirrhotic patients awaiting liver transplantation. Bleeding esophageal varices, spontaneous bacterial peritonitis and hepatic encephalopathy are major complications of cirrhosis and traditional indications for liver transplantation evaluation. However, these complications are not included in the MELD and it is not clear if these complications correlate with MELD score in terms of outcome prediction. This study aimed to investigate the feasibility of cirrhosis-related complication as a prognostic predictor in 290 cirrhotic patients. The MELD score and outcome were compared between patients with and without cirrhosis-related complications. There was no significant difference of the MELD score between patients with (n = 67) and without (n = 223) complications (11.6 +/- 2.9 vs. 12.2 +/- 3.2, p = 0.184). The area under the receiver operating characteristic curve was 0.687 for MELD vs. 0.604 for complications (p = 0.174) at six months, and the area was 0.641 for MELD vs. 0.611 for complications (p = 0.522) at 12 months. A high MELD score and presence of complications had a similar profile of predictive accuracy and both were significant predictors of mortality at six and 12 months in multivariate logistic regression analysis. Patients with cirrhosis-related complications at presentation had a decreased survival compared with those without complications (p < 0.0001). In conclusion, the occurrence of cirrhosis-related complications is a predictor of poor prognosis. While early transplantation referral is recommended, these patients do not necessarily have a higher MELD score and could be down-staged in the MELD era.

De novo malignancies following liver transplantation: a case–control study with long‐term follow‐up

Abstract: Background: Long-term survival data on de novo malignancy are limited following orthotopic liver transplantation (OLT) when compared with controls without malignancies. Methods: Over a 12 yr period at our institution, 50 of 1043 patients (4.8%) who underwent OLT were identified to have 53 de novo malignancies. The clinical characteristics and survival of these patients were retrospectively reviewed and compared with a control cohort of 50 OLT recipients without malignancy matched with the incidence cases by age, year of OLT, sex, and type of liver disease. Results: Chronic hepatitis C, alcohol and primary sclerosing cholangitis were the three leading causes of liver disease. Skin cancer was the most common malignancy (32%), followed by gastrointestinal (21%), including five small bowel tumors, and hematologic malignancies (17%). The cases and controls were not significantly different in the immunosuppressive regimen (p = 0.42) or the number of rejection episodes (p = 0.92). The five- and 10-year Kaplan–Meier survival rates for the cases were 77% and 34%, respectively, vs. 84% and 70%, respectively, for the controls (p = 0.02 by log-rank test). Patients with skin cancers had survival similar to the controls, but significantly better than non-skin cancers (p = 0.0001). The prognosis for patients with gastrointestinal tumors was poor, with a median survival of 8.5 months after the diagnosis. Conclusion: In this single institutional study, de novo malignancies after OLT were uncommon. Patients with non-skin cancer after OLT had diminished long-term survival compared with the controls. Our results differ from other reports in the high incidence of gastrointestinal malignancies with attendant poor prognosis.

Long-term lamivudine monotherapy prevents development of hepatitis B virus infection in hepatitis B surface-antigen negative liver transplant recipients from hepatitis B core-antibody-positive donors.

Abstract: Background: Liver transplantation from hepatitis B core-antibody (HBcAb)-positive donors to hepatitis B surface-antigen (HBsAg)-negative recipients has been associated with a risk of hepatitis B virus (HBV) infection in the absence of antiviral prophylaxis. The aim of this study is to assess the efficacy of long-term lamivudine monotherapy to prevent development of HBV infection in HBsAg-negative recipients of liver allografts from HBcAb-positive donors. Methods: From 315 cadaveric adult liver transplantations performed at our unit between July 1999 and March 2005, 18 recipients (5.7%) received liver allografts from HBcAb-positive donors, 13 of whom were HBsAg-negative pre-transplantation. The recipients consisted of four females and 14 males, age range 28–65 yr (median 49.5 yr). Post-transplantation, HBsAg-negative recipients were administered lamivudine 100 mg daily long term. HBsAg-positive recipients were administered low-dose hepatitis B immunoglobulin (HBIg) and lamivudine according to our usual protocol. Standard post-transplantation immunosuppression was given. Recipients were followed up regularly (range 2–69 months, median 21 months) for development of de novo HBV infection. Results: Ten HBsAg-negative recipients received long-term lamivudine. One patient (HBcAb and HBsAb positive pre-transplant) did not receive lamivudine and, in two patients, lamivudine was discontinued following urgent re-transplantation for primary graft non-function. All 13 of the HBsAg-negative recipients were still alive, with no evidence of HBV infection at the end of follow-up. Conclusion: Long-term lamivudine monotherapy was effective in preventing development of HBV infection in HBsAg-negative liver transplant recipients from HBcAb-positive donors.

Quantification of a low cellular immune response to aid in identification of pediatric liver transplant recipients at high-risk for EBV infection.

Abstract: Objective Uncontrolled EBV infection leading to lymphoproliferative disease is a significant cause of morbidity in pediatric orthotopic liver transplant (OLT) recipients. Herein, we describe the use of a novel immune assay, which quantifies the lymphocyte immune response and correlates the value to risk for EBV infection. Methods All patient data were prospectively collected between 2003 and 2005. The study included 18 pediatric liver transplant recipients, seven males and 11 females with a mean follow-up of 47 months post-OLT. Patient EBV load was monitored using real-time quantitative PCR (qPCR). The ATP release (ng/mL) of CD3+ lymphocytes after mitogenic stimulation with phytohemagluttinin (PHA; Cylex Corporation) was used to quantitate patient immune response. Patients were stratified by EBV load: low ( 4000 copies/microg DNA). Results Patients with low EBV loads had a significantly (p 1000 copies/microg DNA. Further analysis demonstrated that patients with ATP level 4000 copies/microg DNA, when compared with 22% if the ATP level was between 125 and 400 ng/mL or only 15% if >400 ng/mL (p Conclusion In conclusion, this study investigates the use of a lymphocyte activation assay to closely measure the immunosuppression status of pediatric liver transplant recipients. Because measurement of EBV DNA load as a single parameter has a poor positive predictive value for development of PTLD, the association of these assays may be of help in the identification of patients at risk for PTLD.

Predictors of employment after liver transplantation

Abstract: Employment after orthotopic liver transplantation (OLT) indicates recipients’ physical/psychosocial adjustment. Our aim was to determine clinical, socioeconomic and health-related quality of life parameters influencing employment after OLT. Questionnaire on demographics, medical conditions, alcohol and drug use before/after OLT, and a validated 12-Item Short Form Health Survey (SF-12) were mailed to 126 adult OLT patients. Stepwise logistic regression was conducted to identify best predictors of post-OLT employment. Among non-retirees, 49% were employed after OLT. The predictors of employment were: employment status, income, disability status before OLT and Model of End Stage Liver Disease score. These variables had prediction rate of 82%. Individuals working during the five yr prior to OLT were likely to return to work (p 6 months prior to OLT (p $80 000 before OLT compared with <$30 000 (p = 0.036). Patients receiving Social Security Insurance (SSI) payment for ≥6 months prior to OLT, were less likely to work (p = 0.0005). Severity/duration of liver dysfunction prior to OLT did not correlate with employment. Sense of physical health was poorer in those employed after OLT than in unemployed (p = 0.0003). Socioeconomic factors were the most important predictors of post-OLT employment.

Excellent clinical outcomes in primary kidney transplant recipients treated with steroid-free maintenance immunosuppression.

Abstract: Steroid-free maintenance immunosuppression is desirable to eliminate the side effects of chronic corticosteroid use. Complete steroid avoidance or rapid post-transplant steroid withdrawal has recently been used in renal transplant recipients with encouraging results. The present study evaluated the outcome of a steroid-free maintenance immunosuppressive protocol in kidney transplant recipients with at least one-yr follow up. Between April 2002 and October 2004, a total of 301 primary kidney transplant recipients received steroid-free maintenance immunosuppression. The regimen consisted of induction with thymogobulin and prednisone for the first five d. Patients were maintained on Sirolimus and Neoral. Neoral dose was adjusted to target C2 levels and the Sirolimus dose was adjusted to a target rapamycin trough level. All primary kidney transplants (n = 502) performed in the two yr (starting January 2000) prior to institution of the steroid-free regimen and thus maintained on a steroid-based immunosuppressive protocol were used for comparison. One-year patient and death censored graft survival were 93.1% and 98.1% for the steroid-free group vs. 95.2% and 95.2% for the comparator groups (p = ns). The incidence of biopsy-proven acute rejection was 4.9% in the steroid-free group vs. 9.4% in the comparator group (p < 0.01). Two (0.7%) of 301 patients in the steroid-free group lost their grafts because of acute rejection compared with nine (1.8%) patients in the comparator group (p < 0.05). At one-yr post-transplant the mean serum creatinine level was not different between the two groups. There were no significant differences in mean serum cholesterol and triglycerides levels as well as the percentage of patients on lipid lowering agents between the groups. White blood cell counts, daily doses of Neoral and weight gain were significantly lower in the steroid-free group vs. the comparator group. However, more patients in the steroid-free group required erythropoietin and iron therapy for anemia (p < 0.001). We conclude that excellent graft survival with a significantly lower incidence of acute rejection can be achieved using a steroid-free maintenance immunosuppressive protocol consisting of Neoral and Sirolimus.

Radiofrequency thermal ablation of hepatocellular carcinoma before liver transplantation – a clinical and histological examination

Abstract: Background: Radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) is an optional treatment for patients awaiting liver transplantation (LTX). The study evaluates the efficacy of RFA in the explanted liver and its effect on patient outcome. Material and method: Forty-seven patients underwent RFA and were listed for transplant between January 1998 and May 2003. The patients were divided into two groups: transplanted and non-transplanted. Both groups were evaluated in terms of tumor characteristics, recurrence, mortality rate, and time on the waiting list. The ablation sites in the explanted livers were examined for percentage of necrosis by Hematoxylin & Eosin (H&E) stain and by TUNEL stain. Results: Transplantation was carried out in 35 patients (74.5%). Ten patients (21.3%) died before transplant or were removed from the wait list, while two patients (4.2%) are still listed. Mortality and tumor-related mortality were significantly higher in the non-transplanted group. The time spent on the waiting list was longer in the non-transplanted patients (350 vs. 186 d average, p = 0.0345). Thirty-eight ablation sites were examined in the explanted livers. The percentage of tumor necrosis by TUNEL staining was 19.6% higher than that reported by H&E staining. After TUNEL staining, 28 sites (73.7%) had more than 90% necrosis, eight sites (21.0%) had 50–90%, and two sites (5.3%) had less than 50% necrosis. Conclusions: RFA and LTX can be used successfully in HCC patients, and in most cases, tumor necrosis can be achieved with ultrasound-guided RFA. H&E stain tends to under-represent the amount of tumor necrosis on the ablation sites. Survival of RFA patients after LTX is excellent.

Living-donor kidney transplantation: risks of the donor--benefits of the recipient.

Abstract: For patients with end-stage renal disease, kidney transplantation is the optimal therapy. Due to organ shortage, however, most patients have to wait on dialysis for a considerable period of time prior to transplantation. Living-donor kidney transplantation is a valid option to expand the organ pool and to reduce waiting time. The risk-benefit ratio of living-donor kidney transplantation needs to be evaluated critically, as healthy persons voluntarily donate an organ for transplantation. The available data from the literature seem to prove that the donor operation can be performed with a minimal perioperative risk. Regarding the long-term course after kidney donation, the published data suggest that the risk is minimal for well-selected healthy donors who are closely followed postoperatively. The potential donor, however, needs to be completely informed regarding the potential short- and long-term risks of kidney donation prior to the planned procedure. From the recipient point of view, transplantation of a kidney from a living donor is a very good if not the optimal option, as the short- and long-term outcomes seem to be favorable compared with cadaveric kidney transplantation. With donor safety being constantly monitored, it seems to be justified to further pursue living-donor kidney transplantation programs.

Longitudinal testing of 266 renal allograft patients for HLA and MICA antibodies: Greenville experience.

Abstract: 1. From the analysis of 266 Greenville kidney recipients, we found that almost every patient who had graft failure had HLA antibodies (93%), while less than half of patients with currently functioning graft had antibodies (46%). 2. The difference between failed grafts and successful grafts was even greater for de novo antibodies (60% vs. 14%) and greatest for donor-specific antibodies (75% vs. 9%). 3. The incidence of HLA-DQ antibodies was surprisingly high, and the majority was donor-specific. Now that the improved detection beads are available, the effect of DQ antibodies on transplants should be further studied. 4. MICA antibodies were found in 12% of total 266 patients, and found to be more frequent (21%) in patients with graft failure than in patients with successful graft (7%). Almost all patients with MICA antibodies also had HLA antibodies. 5. From the sequential sera testing, we were able to see that, in most cases, antibodies are produced long before the failure and before the elevation of serum creatinine. 6. Periodic testing of sera by single antigen beads enable us to distinguish de novo antibodies from preformed antibodies and to determine whether they are donor-specific. This is important since de novo DSA are most detrimental to graft.