摘要:

Background.The quality of life, psychologic sequelae, and functional status of liver transplant recipients with recurrent hepatitis C virus (HCV) hepatitis have not been well defined.Methods.Perceived quality of life, psychologic distress, depression, adaptive coping, and functional status were prospectively assessed in 59 liver transplant recipients at baseline (before transplantation) and 6 and 12 months after transplantation; comparisons were made between patients with recurrent HCV hepatitis and all other patients.Results.Recurrent HCV hepatitis developed in 41% (14/34) of the patients with HCV. At 6 months, the patients with recurrent HCV hepatitis had significantly lower functional status (P=0.013) and experienced less gain in physical functioning from baseline than other patients (P=0.02). Quality of life, depression, and psychologic distress were not different at 6 months for patients with recurrent HCV hepatitis compared with all other patients. At 12 months, the patients with recurrent HCV hepatitis had significantly lower quality of life (P=0.003), greater depression (P=0.045), higher psychologic distress (P=0.05), and lower physical functioning (P=0.008) than all other patients.Conclusion.Recurrent HCV hepatitis in liver transplant recipients is associated with impairment in quality of life, functional status, and greater depression compared with patients who did not have HCV and those without HCV recurrence.

ISSN:0041-1337    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Background.Cadaveric liver donors are scarce in Hong Kong, and the application of liver transplantation to high-urgency patients is limited. We evaluated the use of grafts from living donors in this setting.Methods.From July 1994 to January 1998, 49 consecutive adult patients who were intensive care unit-bound because of acute or chronic liver failure were put on a high-urgency list for liver transplantation. Family members were not solicited for living donation, and the initiation and decision for living donor liver transplantation (LDLT) was based on the donor's voluntary intent. Assessment of the living donor, including blood tests, computed tomographic volumetry, and angiography, was performed only after informed consent was executed.Results.In 25 of 49 (51%) patients, no family member volunteered as living donor; 23 died awaiting donor organs, and 2 received a cadaveric graft. Twenty-four (49%) patients had 36 family members who volunteered as living donors. Before evaluation of living donor was completed, two patients received a cadaveric liver transplant. LDLT was not performed in nine patients because of recipient contraindications (n=4), ABO blood group incompatibility (n=3), and withdrawal of donor (n=2). Eight of these nine patients died, and one received a cadaveric liver graft. The remaining 13 (27%) patients received grafts from living donors. Four of 5 (80%) patients who underwent cadaveric liver transplantation and 11 of 13 (85%) who underwent LDLT survived. Thus, emergency transplantation from living donors increased the applicability of liver transplantation from 10% to 37%, and the survival rate after emergency LDLT (85%) was superior to that of the remaining patients (11%).Conclusions.When cadaveric organ donation is scarce, emergency liver transplantation from living donors can be applied to high-urgency adult patients.

ISSN:0041-1337    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Background.Liver transplant recipients for hepatitis C virus (HCV)-related cirrhosis usually remain anti-HCV-seropositive after transplantation. The aim of this study was to characterize, longitudinally, the profile of HCV-specific antibodies and cryoglobulins in liver transplant recipients with recurrent HCV infection.Methods.Serial serum samples were collected prospectively before, at 1 month after, and at 12 months after transplantation for HCV cirrhosis in 30 patients infected with genotype 1. The antibodies against HCV envelope proteins (E1 and E2) were quantitated by enzyme-linked immunosorbent assay and antibodies against core, E2/hypervariable region I (HVRI), NS3, NS4, and NS5A antigens by a line immunoassay. Sera were also tested for cryoglobulins.Results.The titer of each anti-HCV antibody had fallen at 1 month after transplantation (P<0.05) with the exception of anti-E1 levels, which had risen in 16 patients with acute hepatitis C at that time (P=0.01). Anti-E1 and anti-E2 titers, but not antibodies against other HCV antigens, increased to pre-transplantation levels or higher at 12 months, which correlated with serum HCV RNA levels. Cryoglobulinemia was present in nine patients after transplantation (30%) and was associated with lower anti-E1 levels (P=0.04) and more severe graft damage.Conclusions.The early increase in antibodies to HCV envelope proteins in correlation with viremia suggests that the envelope-specific humoral immune response may be directly stimulated by HCV replication. Anti-E1 levels may be a useful marker in monitoring patients with recurrent HCV infection.

ISSN:0041-1337    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Background.The clinical significance of biopsies showing both rejection and isometric tubular vacuolization has not been well defined in the literature.Methods.The clinical picture, sequential histopathologic findings, and response to therapy were compared between 24 renal allograft biopsies showing both tubular vacuolization and rejection and 14 biopsies showing vacuolization alone.Results.The rejection was categorized as grade 1 in 4/24 (16.6%), grade 2A in 10/24 (41.6%), and grade 2B in 10/24 (41.6%) cases (Banff schema, 1993-1995). Treatment with additional steroids and tacrolimus led to a decrease in the interstitial inflammation score (2.6±0.1 to 1.3±0.1,P<0.001), tubulitis score (2.6±0.1 to 1.1±0.1,P<0.001), and serum creatinine (4.4±2.2 mg/dl to 3.3±2.6 mg/dl,P=0.001). Complete response, partial response and no response to antirejection therapy were observed in 16/24 (66.7%), 3/24 (12.5%), and 5/24 (20.8%) patients, respectively. Although there was a rise in the plasma (1.4±0.2 ng/ml to 2.8±0.3 ng/ml,P<0.001) and whole blood (16.5±2.8 ng/ml to 31.2±5.7 ng/ml,P<0.001) tacrolimus levels, repeat biopsy showed no change in the size or extent of tubular vacuolization (mean score 2.88±0.19 vs. 2.83±0.21). The morphologic characteristics of the tubular vacuoles in these cases did not differ from those observed in 14 cases of tacrolimus nephrotoxicity not complicated by rejection.Conclusion.Patients with concurrent acute rejection and tubular vacuolization usually benefit from increased immunosuppression. The pathogenesis of the vacuolization in this clinical setting is not clear, but may reflect immune-mediated tubular injury.

ISSN:0041-1337    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Background.The prevalence and clinical significance of antiphospholipid antibodies (APAs) have not been extensively studied in non-systemic lupus erythematosus (non-SLE) renal transplant recipients.Methods.To further define the prevelance and clinical significance of APAs in non-SLE renal transplant recipients and the appearance of dialysis-related APAs after renal transplantation, we conducted a retrospective study on 178 renal transplant recipients. Documentation of anticardiolipin antibodies (ACAs) and lupus anticoagulant in non-SLE renal transplant recipients, retrospective documentation of ACAs on pretransplant frozen plasma and standardized collection of demographic characteristics and posttransplant history of thrombosis were assessed.Results.Fifty of 178 patients (28.1%) had APAs. Transplantation duration was shorter and hemodilysis duration was longer in patients with APAs. A posttransplant history of both venous and arterial thrombosis was more frequent in patients with posttransplant APAs (respectively, 18% vs. 6.2% [P<0.001] and 8% vs. 2.3% [P<0.001]). Pretransplant sera were available from 55 patients. Most of patients with posttransplant ACAs had ACAs in the pretransplant period (85%). Pretransplant ACAs were associated with a posttransplant history of venous thrombosis (P<0.001).Conclusions.Our study demonstrates a high prevalence of APAs in non-SLE renal transplant recipients. Most of them have been acquired in the pretransplant period. Both pretransplant ACAs and posttransplant APAs are associated with posttransplant episodes of thrombosis. Further studies are required to determine the interest of prophylactic measures.

ISSN:0041-1337    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Background.With the introduction of ganciclovir, the clinical pattern of cytomegalovirus (CMV) disease has changed; CMV disease recurrence after successful treatment of the initial episode has emerged as a more common problem. We studied CMV disease recurrence in kidney transplant (KTx) and simultaneous kidney-pancreas transplant (SPK) recipients, and identified risk factors for recurrence.Methods.Between January 1987 and December 1995, of 1272 KTx and 287 SPK recipients, 332 developed CMV disease and were treated with a 14-day course of i.v. ganciclovir, followed by a 10-week course of oral acyclovir. Among these 332 recipients, 103 (31%) developed CMV disease recurrence more than 30 days after treatment for the initial episode; this group was compared with those recipients who did not develop recurrence (n=229). Risk factors examined were age, presence of diabetes, type of transplant (KTx vs. SPK), donor source (cadaver vs. living donor), treatment for acute rejection, pretransplant CMV serologic status, evidence of tissue-invasive CMV, and treatment of the initial episode with human immune globulin in addition to ganciclovir.Results.Univariate analysis found that patients with recurrence were more likely to be diabetic (70.9% vs. 53.7%;P=0.04), to have undergone an SPK (39.8% vs. 20.5%;P=0.004), to have received a cadaver organ (78.6% vs. 61.6%;P=0.002), and to have received treatment for acute rejection (78.6% vs. 59.8%;P=0.001). Using multivariate analysis, two statistically significant risk factors were found: receiving a cadaver organ (relative risk [RR]=1.90;P=0.03) and treatment for acute rejection (RR=2.02;P=0.008). Diabetes (RR=1.44;P=0.18) and a cadaver SPK transplant (RR=1.55;P=0.12) tended toward increased risk for recurrence, but the difference did not reach statistical significance. The remaining variables were not significant. Interestingly, CMV recurrence did not significantly diminish 5-year graft survival (52.0% vs. 54.4%;Pnot significant) or patient survival (67.0% vs. 68.3%;Pnot significant) rates.Conclusions.CMV disease recurs in roughly one-third of KTx and SPK recipients after treatment of the initial episode with ganciclovir. A cadaver organ source and treatment for acute rejection were the most significant clinical risk factors for recurrence. Clinical predictors of recurrence such as these may help to identify those recipients who need more intensive therapeutic and prophylactic regimens.

ISSN:0041-1337    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Background.Renal allografts are a frequent site of subclinical cytomegalovirus (CMV) infection diagnosed by culture, but histologic inclusions occur in less than 1% of biopsies. The natural history of this subgroup of patients has been reported only occasionally, mostly before the availability of ganciclovir therapy.Methods.We analyzed the clinical parameters and pathologic findings in 10 patients with CMV inclusions at allograft biopsy.Results.The patients were 29-72 years old, and 9 of 10 (90%) had previous episodes of acute rejection, 3 of whom needed OKT3 administration. Histopathologic examination of the allografts showed interstitial inflammation with tubulitis in 7 of 10 (70%) patients; in 3 of 10 (30%) patients, viral inclusions were present in the glomerular capillary endothelia without any associated inflammatory response. Morphologic criteria for acute transplant glomerulopathy or proliferative glomerulonephritis were not satisfied. Extrarenal viral inclusions were documented in the gastrointestinal tracts of 2 of 10 (20%) patients. The patients were treated with reduced immunosuppression and ganciclovir. Five patients lost their grafts 56.6±86.6 days (range, 4-210 days; median, 21 days) after initial diagnosis. The serum creatinine in the remaining five patients was 3.3±2.0 mg/dl (range, 1.2-6.5 mg/dl; median, 2.5 mg/dl) 77±16 days (range, 56-101 days; median, 77 days) after transplantation. Histopathologic examination showed no residual viral inclusions in 5 of 7 (71.4%) follow-up specimens available for examination.Conclusions.CMV inclusions in renal allograft biopsies typically occur after treatment for rejection. Ganciclovir eradicates replicative virus, but graft outcome is determined by coexisting acute rejection and chronic allograft nephropathy. Graft loss primarily attributable to CMV was not observed.

ISSN:0041-1337    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Background.Asymptomatic polyoma virus infection documented by urine cytology or serology is well known, but the clinical course of biopsy-proven interstitial nephritis is not well defined.Methods.Twenty-two cases were identified by histology, immunostaining, in situ hybridization, electron microscopy, or polymerase chain reaction.Results.The clinical features mimicked acute rejection (n=19), chronic rejection with incidental diagnosis at nephrectomy (n=2), or drug toxicity (n=1). Histology showed homogenous intranuclear inclusions. In situ hybridization showed BK virus (BKV) to be the predominant species, but polymerase chain reaction documented JC virus co-infection in one of five cases so tested. Electron microscopy in seven cases showed 20-51-nm virions. The two cases diagnosed at nephrectomy received no therapy. Initial antirejection therapy in 12 cases led to clearance of the virus in 1/12 (8%), partial therapeutic response in 3/12 (25%), and graft loss in 8/12 (67%) cases. The last recorded creatinine in patients with functional grafts ranged from 1.9 to 7.0 (median: 4.5) mg/dl, 0.4-45 (median: 4.0) months after initial diagnosis. The remaining eight cases treated by reduction of immunosuppression at the outset have been free of graft loss for 0.2-10.0 (median: 4.8) months since diagnosis, and clearance of virus has been documented in three of six (50%) cases. The serum creatinine in these patients is 1.7-6.0 (median: 2.4) mg/dl, 0.2-10 (median: 4.8) months after diagnosis. Follow-up biopsies performed 1-23.5 months after diagnosis show chronic allograft nephropathy.Conclusions.Polyoma virus tubulo-interstitial nephritis-associated graft dysfunction usually calls for judicious decrease in immunosuppression and monitoring for acute rejection. Development of methods to serially quantify the viral load in individual patients could potentially improve clinical outcome.

ISSN:0041-1337    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Background.Acute rejection is still a major problem in renal transplantation and is one of the most important causes of chronic graft dysfunction and late graft loss. Selective immunosuppression with a humanized antibody against the α-chain of the interleukin (IL)-2 receptor (CD25) was evaluated to demonstrate the efficacy of this type of immunoprophylaxis in combination with dual immunosuppression.Methods.We studied the effect of daclizumab, a humanized monoclonal antibody against the α-chain of the IL-2 receptor, in a randomized double-blind, prospective phase III clinical trial in 275 patients receiving a first cadaveric renal allograft. Among them 111 (83%) in the placebo arm and 116 (82%) in the daclizumab arm received the full regimen of five doses (1.0 mg/kg) every other week. Baseline immunosuppression consisted of cyclosporine and corticosteroids.Results.At 6 months, 39 (28%) of the patients in the daclizumab group had biopsy-proven rejections, as compared with 63 (47%) in the placebo group (P=0.001). The need for additional antilymphocyte therapy, antithymocyte globulin, antilymphocyte globulin (ATG, ALG, OKT3) was also lower in the daclizumab group (8% vs. 16%,P=0.02), and they required significantly lower mean (± SD) cumulative doses of prednisone (3750±1981 mg vs. 4438±2667 mg in the placebo group,P=0.01). Graft function was significantly better (P=0.02) in the daclizumab group (graft function rate: 58 vs. 51 ml/min, mean) as was patient survival (P=0.01, 99% vs. 94%). No specific adverse events were observed in daclizumab-treated patients. Patients receiving daclizumab experienced fewer cytomegalovirus infections (18% vs. 25%), and none died from severe infectious complications, compared to four patients in the placebo arm. No patient in the daclizumab group had a lymphoproliferative disorder or any other form of immunosuppression-related tumor during the first year after transplant.Conclusions.Administration of daclizumab in addition to dual immunosuppression therapy significantly reduced biopsy-proven acute rejection after renal transplantation, improved patient survival, and did not add to the toxicity of the immunosuppressive regimen.

ISSN:0041-1337    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Background.Pretransplantation injection of freshly heparinized donor blood (donor-specific blood transfusion, or DST) significantly prolongs the survival of hepatic allografts from ACI(RT1a) to LEW(RT11) rats. We investigated hepatocyte growth factor (HGF) expression in rat hepatic allografts of recipients pretreated with or without DST.Methods.The levels of HGF mRNA and protein in hepatic allografts were determined after transplantation. The localization of HGF+cells was identified with a rat anti-HGF monoclonal antibody.Results.Plasma HGF concentrations in transplanted rats treated with DST were significantly and persistently increased compared to untreated rats with hepatic allografts. The number of HGF+cells in hepatic allografts of recipients pretreated with DST on day 14 was significantly greater than that in allografts of untreated recipients on day 7. HGF+cells were also found in the marginal zone and red pulp of recipient spleens. Northern blot analysis revealed the presence of three HGF+cell phenotypes: HGF+ED1+, HGF+ED2+, and HGF+ED1-ED2-. Most HGF+cells were ED1-ED2-. In situ hybridization demonstrated HGF mRNA in the mononuclear cells in the portal and sinusoidal areas as well as the marginal zone and red pulp in both DST-treated and untreated recipient spleens.Conclusions.Enhanced HGF expression in rat hepatic allografts is associated with immunologic unresponsiveness induced by DST.

ISSN:0041-1337    

出版商:OVID    

年代:1999

数据来源: OVID