摘要:

Background.Chronic viral hepatitis averages 15% to 20% in heart transplant patients. Several studies have shown that ursodiol may improve liver biochemistry in patients with chronic hepatitis. We used a double-blind randomized controlled trial to evaluate the effect of ursodiol in heart transplant patients with chronic viral hepatitis.Methods.Thirty heart patients with chronic viral hepatitis B, C, or non-A-G received ursodiol, 800 mg per day (group 1), and 30 received placebo (group 2) for 12 months. Endpoints were improvement in liver biochemical tests and in total Knodell score. Intent-to-treat and per-protocol analyses were performed.Results.At entry, both groups were comparable for all of the studied parameters. During the study period, serum alanine aminotransferase, aspartate aminotransferase, and &ggr;-glutamyl transpeptidase variations were not different between group 1 and group 2 patients. Knodell score improved in 20% of group 1 patients and in 43% of group 2 patients (NS). Adverse events or mortality were not different in the two groups during the study period. Similar results were observed by intent-to-treat and per-protocol analyses.Conclusions.A 12-month course of ursodiol therapy had no effect on liver enzymes or liver histology in heart transplant patients with chronic hepatitis.

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background.A more rapid and aggressive course of hepatitis B virus (HBV)-related and hepatitis C virus (HCV)-related infection in organ transplant recipients has been described. Interferon alfa is the most accepted drug for treating HBV and HCV chronic infections. However, the use of interferon alfa-N3 has been contraindicated in heart transplant (HTx) recipients because of the hypothesized greater risk of triggering acute cellular rejection. The aim of this clinical pilot study was to evaluate tolerability, safety, and efficacy of natural leukocyte interferon alfa in the treatment of chronic HBV and HCV in HTx recipients.Methods.Seven HTx recipients were enrolled in the study: two with HBV, four with HCV, and one with combined HBV-HCV chronic infection. The patients had a mean follow-up after heart transplantation of 8.5±3 years, before starting interferon alfa-N3 treatment at a dose of 6 MU three times per week, intramuscularly for 12 months.Results.All patients completed the treatment with no major side effects. No unexpected episodes of acute cellular rejection were observed during the treatment. Mean aminotransferase serum levels were significantly lower than before transplantation at 3 (P<0.03), 6 (P<0.02), and 12 (P<0.02) months of treatment and at the 12-month follow-up (P<0.02). A complete and sustained response was achieved in all subjects with HBV-related chronic hepatitis, whereas sustained virologic response was observed in one of four HCV patients.Conclusions.The preliminary data emerging from our study indicate that natural leukocyte interferon alfa-N3 can be safely administered in HTx recipients with chronic HBV or HCV viral hepatitis. Further studies with larger numbers of patients are needed to assess the efficacy of interferon alfa-N3 on HCV virologic response.

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background.Previous studies have suggested an increased risk of Epstein-Barr virus-associated posttransplant lymphoproliferative disorder (EBV-PTLD) in patients receiving tacrolimus for immunosuppression. We hypothesized that after correction for confounding variables, immunosuppression with tacrolimus is not associated with an increased risk of EBV-PTLD.Methods.Potential cases of EBV-PTLD, identified by chart review, were independently ascertained by three clinicians and defined using published criteria. Agreement in diagnosing EBV-PTLD was measured using Kappa coefficients. Unadjusted and adjusted relative risk estimates were determined using proportional hazards regression.Results.Twenty-three cases of EBV-PTLD were identified in 221 patients, a proportion of 10.4% (95% confidence interval [CI]: 6.4%–14.4%). Multivariable analysis revealed that immunosuppression with tacrolimus was associated with an increased risk of EBV-PTLD (relative risk 3.10: 95% CI: 1.21–7.92), as was age at transplantation as a continuous variable (parameter estimate −0.15,P=0.03). Kappa coefficients in diagnosing EBV-PTLD and subclassifying as neoplastic and non-neoplastic EBV-PTLD were 0.73 (95% CI: 0.54–0.93) and 0.54 (95% CI: 0.40–0.68), respectively. Patients with neoplastic PTLD demonstrated a lower probability of survival than patients with non-neoplastic PTLD and non-cases.Conclusions.Immunosuppression with tacrolimus and young age at transplantation are associated with an increased risk of EBV-PTLD in children undergoing liver transplantation, although we cannot exclude detection bias as an explanation for this observed increase. Good agreement between observers can be achieved using previously published criteria for defining EBV-PTLD. Patients with neoplastic EBV-PTLD may have a worse prognosis, and thus identification of risk factors for the development of this subtype of the disorder may be more important.

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background.Cardiovascular disease is the most common cause of death among renal transplant recipients (RTRs). Impaired fibrinolytic capacity caused by an increase in plasminogen activator inhibitor type 1 (PAI-1) levels is involved in the onset of atherosclerosis and thrombotic complications. Long-term steroid treatment may induce arterial hypertension and metabolic and prothrombotic changes (including up-regulation of PAI-1 synthesis), which increase the cardiovascular risk. We evaluated plasma fibrinolytic behavior in two groups of RTRs treated with different immunosuppressive regimens.Methods.Twenty-seven RTRs were randomized to receive long-term (17 patients) or perioperative short-term (10 patients) steroids in addition to immunosuppression with cyclosporine A plus everolimus (Certican; Novartis, Basel, Switzerland) (7 patients) or FK506 plus mycophenolate mofetil (20 patients). In each patient, fibrinolytic capacity was studied with the 20-min venous occlusion test 1 and 6 months after transplantation. The following were assayed: euglobulin lysis time, tissue-type plasminogen activator antigen, and PAI-1 antigen and activity.Results.One month after transplantation, a severe impairment of fibrinolytic capacity, mainly caused by an increase in PAI-1 antigen and activity levels, was seen in patients with and without steroid treatment. Six months after transplantation, an improvement in fibrinolytic potential as the result of a decrease in PAI-1 levels was observed only in patients without steroid therapy. None of the steroid-treated patients demonstrated PAI-1 values correlating with body mass index, blood pressure, and metabolic parameters, thus confirming the effect of exogenous factors on PAI-1 expression. Moreover, all patients revealed a slight impairment of stimulated endothelial tissue-type plasminogen activator release, regardless of any steroid treatment, which was probably attributable to calcineurin inhibitor-induced endothelial dysfunction.Conclusions.Our study suggests that steroid-free immunosuppression is associated with a better fibrinolytic capacity in RTRs. This finding may contribute toward reducing the risk of cardiovascular events.

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background.Chronic allograft nephropathy (CAN) represents the most common cause of late graft loss. Nephrotoxicity from chronic use of calcineurin inhibitors (CNI) has the potential to contribute to CAN. The present investigation aimed to evaluate the impact of early CNI withdrawal on kidney graft function and structure at 1 year in sirolimus (SRL)-treated patients.Methods.Forty consecutive kidney transplant recipients were initially treated with corticosteroids, cyclosporine A (CsA), and SRL (2 mg/day). After 3 months, patients were randomly assigned to either continue the same treatment (group I) or to withdraw CsA and continue SRL (group II). All patients underwent kidney graft biopsy immediately after graft reperfusion (0-hr biopsy) and 12 months after engraftment.Results.Baseline graft biopsy showed a higher degree of renal damage in group II patients (total score, 4±1.6 vs. 2±0.9;P<0.05). Twelve months after engraftment, CAN was diagnosed in 55% of all patients, of whom 64% were in group I and 36% in group II. CAN lesions were scored as moderate to severe in 90% of group I patients but only 32% of group II patients (P<0.05). A vascular score greater than or equal to 2 occurred in 90% of group I patients and in 38% of group II patients (P<0.05). At 1 year, group I patients showed a significantly worse kidney graft function (serum creatinine, 2.0±0.3 vs. 1.3±0.3 mg/dL; creatinine clearance, 54±14 vs. 66±17 mL/min; bothP<0.002).Conclusions.These results suggest that early withdrawal of CsA is a safe option, which allows a significant reduction of chronic histologic damage, particularly vascular injury, of cadaveric kidney allografts.

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background.Wilson’s disease associated with severe liver disease is effectively cured by orthotopic liver transplantation (OLT). However, there are also anecdotal reports of improved or resolved neurologic symptoms after OLT in patients with stable or normal liver function. Side effects with conventional chelating agents are common, and it has been suggested that OLT should be considered in patients with severe progressive neurologic symptoms. However, the decision to apply this therapeutic modality to a subgroup of patients without significant liver disease is a quality-of-life issue.Methods.Long-term follow-up and quality-of-life data were obtained prospectively for 24 patients who underwent OLT between 1988 and 2000 for Wilson’s disease associated with severe liver disease. In long-term survivors, quality of life was assessed using the 36-Item Short Form 36 Health Survey Questionnaire.Results.One patient who had multiorgan failure before OLT died within 24 hr of surgery and two patients died within 1 year because of immunosuppressant-related complications. There have been no deaths or graft loss in patients who have undergone transplantation since 1994, and after a median follow-up of 92 months, all survivors have satisfactory graft function (5-year patient and graft survival, 87.5%), with quality-of-life scores (assessed in 86% of survivors) comparable to age- and sex-matched controls from the general population.Conclusions.The authors’ results suggest that liver transplantation can be safely performed in patients with Wilson’s disease, with excellent long-term results and quality of life. Further study of the utility of liver transplantation in the management of patients with severe neurologic symptoms is justified.

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background.The human T-cell lymphotrophic virus (HTLV) causes adult T-cell leukemia-lymphoma, tropical spastic paraparesis-HTLV type I, and associated myelopathy.Methods.An analysis was performed of serum samples from a multiorgan donor and the five recipients. Also studied was the donor’s family and the partner of one of the renal recipients. Serologic detection of anti-HTLV antibodies was carried out by enzyme immunoassay and Western blot to confirm and discriminate between HTLV types. Analysis of proviral DNA was performed by polymerase chain reaction and sequenced in the long terminal repeat region and theenvgene. Peripheral blood mononuclear cell samples from all the recipients of the HTLV-I–positive organs and the donor’s mother were studied.Results.Two years after transplantation, three organ recipients positive for antibodies to HTLV-I were detected (two kidney transplants and one liver). All the recipients’ serum samples were negative at the time of transplantation except those from the multiorgan donor. The donor’s mother was born in Venezuela and was confirmed positive for antibodies to HTLV-I. The remaining family members were negative. HTLV-I DNA sequences were recovered, amplified, and sequenced from all the samples from the HTLV-I–positive recipients and the donor’s mother. The homology of HTLV-I sequences was 100% in all cases.Conclusions.The authors are reporting the first documented case of HTLV-I infection in several transplant recipients sharing the same donor. The donor was infected by vertical transmission. HTLV-I infection has devastating consequences for some immunocompromised organ recipients. This emphasizes the need for a systematic survey of HTLV antibodies in all potential donors.

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background.Preemptive therapy of human cytomegalovirus (HCMV) infections has gained popularity in transplantation centers. However, standardized protocols are not available. In particular, whether a qualitative molecular assay for detection of a late (pp67) HCMV mRNA represents a valuable alternative to quantitative antigenemia remains to be defined.Methods.Overall, 82 heart (HTR) and lung (LTR) transplant recipients were randomized into two arms, where therapy was guided by qualitative pp67 mRNA NASBA (40 patients) or quantitative antigenemia (42 patients). In the NASBA arm, both primary and recurrent infections were treated upon first confirmed positive NASBA result. In the antigenemia arm, primary infections were treated upon first confirmed positive result, while recurrent infections were treated upon cutoff of 100 pp65-positive leukocytes. In both arms, therapy was stopped upon virus disappearance. Primary endpoint was duration of therapy.Results.The number of treated/infected patients was significantly higher in the NASBA arm (25/30 vs. 15/39;P=0.015), as was the number of treated/relapsing patients (5/8 vs. 1/11;P=0.040), whereas the number of HCMV-infected/total number of patients was significantly higher in the antigenemia arm (39/42 vs. 30/40;P=0.026). Thus, in the NASBA arm, although the median duration of therapy was shorter compared to antigenemia (17 vs. 21 days,P>0.05), the overall number of days of therapy was significantly higher. No patient developed HCMV disease.Conclusion.pp67 mRNA NASBA can safely replace antigenemia, with some apparent advantages (semiautomation and objectivity of test results) and disadvantages (overtreatment of patients and greater duration of overall treatment).

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background.Although the outcome of liver transplantation has improved significantly during the past two decades, graft loss caused by chronic rejection after liver transplantation still occurs in 2% to 20% of recipients. The overall incidence of chronic rejection is also reported to be low in adult recipients, and risk factors have been identified. Chronic rejection is associated with the inability to maintain baseline immunosuppression. Additionally, the diagnoses of primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis, hepatitis B virus, and hepatitis C virus, common indications for liver transplantation in adults, are associated with a higher incidence of chronic rejection. Fortunately, these diagnoses are rarely seen in children. Little is known about chronic rejection in long-term pediatric liver transplant survivors. The purpose of this longitudinal study was to examine the incidence of biopsy-proven chronic rejection in long-term survivors of primary pediatric liver transplantation under tacrolimus-based immunosuppression.Methods.From October 1989 to December 1992, 166 children (boys=95, girls=71; mean age=5.0±2.9 years) received a primary liver transplant. These patients were followed until March 2000 with a mean follow-up of 9±0.8 (range, 7.4–10.4) years. All liver biopsy specimens and explanted grafts were evaluated for evidence of chronic rejection using the International Banff Criteria.Results.The mortality rate during the follow-up period was 15% (n=25). Retransplantation was required in 11% (n=18) of recipients. Actuarial patient and graft survival rates at 10 years were 84.9% and 80.1%, respectively. There were 535 liver biopsy samples available for evaluation, including the 18 explanted allografts. Biopsy specimens of three other functioning allografts showed evidence of chronic rejection. Immunosuppression had been discontinued or drastically reduced in these recipients because of life-threatening infections, noncompliance, or both. On restoring baseline immunosuppression, all three children had normalized liver function and the allografts were maintained; the liver transplant patients who are alive currently have normal liver functions.Conclusion.The findings of this study suggest that chronic rejection does not occur in pediatric liver transplant recipients receiving tacrolimus-based immunosuppression, provided baseline immunosuppression is maintained.

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background.Patient fitness at the time of organ allocation has an impact on graft survival equivalent to the effect of human leukocyte antigen (HLA) matching. The variation between institutions in assessment of fitness is not known, nor is the potential impact on mean graft survival of incorporating patient fitness into local adult cadaveric-kidney transplant-allocation algorithms.Methods.Data from the Collaborative Transplant Study (CTS, 1985–2000) were reviewed. Quantitative criteria (QC) of patient fitness based on national transplant society guidelines were compared with subjective categorization (SC) of each patient on the current local transplant waiting list (n=109) determined by their supervising nephrologist.Results.Five-year cadaveric graft survival was 70%, 61%, and 53% for good-, moderate-, and poor-risk patients in the CTS data set (n=102, 612), equivalent to half lives of 12.7, 9.8, and 8.7 years, respectively, with similar results from the local program. The distribution of local waiting-list patients into fitness categories A (good), B (moderate), C (poor), and D (unacceptable) was 51%:31%:13%:5% by SC and 25%:40%:27%:8% by QC. At one hospital, 61% (n=51) of patients were classified category A by SC, and falling to 16% by QC (P<.0001). Compared with preferential category A recipient allocation, an unrestricted allocation policy was estimated to sacrifice 1.5 years of overall program-mean graft survival.Conclusions.Use of QC may reduce the variation in subjective patient assessment seen between institutions. Any proposed changes in organ allocation methods should address the “equity versus efficiency” balance in an open fashion and predict the impact on the overall graft survival for the program by quantifying the “equity penalty.”

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID