Neuropsychiatric complications after liver transplantation: role of immunosuppression and hepatitis C.

Neuropsychiatric complications are an important source of morbidity following orthotopic liver transplantation. Etiology of liver disease and type of immunosuppression are possible related factors. The aim of this study was to describe the prevalence of neuropsychiatric complications after liver transplantation, the role of immunosuppression, and the association between these and specific liver diseases such as hepatitis C. One hundred twenty-eight patients with liver transplants were studied. Tacrolimus was the primary immunosuppressant in 101 patients and cyclosporine in 27 patients. Seventy-five complications in 49 patients (38.2%) were reported. In 43 patients, the etiology was associated with immunosuppression: 36 on tacrolimus and 7 on cyclosporine (P = 0.34). Seventeen and four-tenths percent of patients with hepatitis C and 4.6% of patients without hepatitis C developed depression (P = 0.02). There is no difference between types of primary immunosuppression and neuropsychiatric complications. There is a significantly greater incidence of depression in patients transplanted for hepatitis C.

Observations regarding the use of sirolimus and tacrolimus in high-risk cadaveric renal transplantation.

BACKGROUND: Balancing the risk of acute rejection (AR) with drug-induced toxicities complicates the selection of the optimal immunosuppressive regimen, especially in the high-risk renal transplant recipient. This study was designed to determine the optimal dosage combinations of tacrolimus and sirolimus in a high-risk cadaveric renal transplant population. METHODS: Primary cadaveric renal transplant recipients were randomly assigned to receive either standard tacrolimus (trough levels of 10-15 ng/mL) plus reduced sirolimus (trough levels of 5-10 ng,mL) (Group I) or to receive reduced tacrolimus (trough levels of 5-10 ng,mL) plus standard sirolimus (trough levels of 10-15 ng/mL) (Group II). All patients received Thymoglobulin induction and steroids. RESULTS: Thirty-nine (16 in Group I and 23 in Group II) high-risk renal transplant recipients (100% cadaveric donors, 79% African-American recipients, and 59% delayed graft function) are the subjects of this report. At 6 months, the patient survival rate was 94 and 100% and the graft survival rate was 94 and 83% in Groups I and II, respectively. The incidence of biopsy-proven AR was 6 and 5% in Groups I and II, respectively. Eight patients (50%) in Group I required discontinuation of tacrolimus, seven because of biopsy-proven tacrolimus nephrotoxicity and one secondarily to interstitial pneumonitis. Wound complications were the most frequent adverse event reported in both groups. CONCLUSIONS: The combination of tacrolimus and sirolimus was associated with a low risk of AR in this cohort of high-risk renal transplant recipients. However, 50% of patients who received standard tacrolimus and reduced sirolimus combination had to be discontinued from the regimen because of biopsy-proven nephrotoxicity. These preliminary results provide evidence that sirolimus should not be added to tacrolimus without dosage adjustments. We have discontinued recruitment of patients to the standard tacrolimus and reduced sirolimus combination and we have tightened our criteria for selection of marginal donor kidneys with our high-risk renal transplant recipients.

Liver transplantation for acute Budd-Chiari syndrome in identical twin sisters with Factor V leiden mutation.

BACKGROUND: Budd-Chiari syndrome (BCS) is uncommon in the children. The cause of BCS comprises several diseases leading to thrombophilia. Activated protein C resistance as a result of a single gene mutation in factor V, the so called factor V Leiden (FVL), is the most common cause of thrombophilia. METHODS: We report a simultaneous occurrence of BCS in identical twin sisters of 13 years of age with heterozygous FVL mutation. RESULTS: One sister presented with acute BCS leading to fulminant hepatic failure. She underwent liver transplantation with subsequent normalization of activated protein C resistance. The other twin sister, who was diagnosed with extensive thromboses of the inferior vena cava, portal vein, and hepatic veins, was successfully managed by aggressive chemical and mechanical thrombolysis followed by therapeutic anticoagulation. Genomic DNA studies confirmed heterozygosity of FVL mutation in the sisters' father and older brother. CONCLUSIONS: The exact cause of the BCS in children should be thoroughly and rapidly investigated, and, if necessary, immediate family members should also be tested for genetic defects in factor V or concomitant thrombophilia.

Perceptions of the donation process from adult-to-adult living liver donors.

BACKGROUND: Donor safety and the impact on quality of life continue to concern transplant centers as living liver transplantation increases. METHODS: Living liver donors participated in a focus group to discuss their perceptions of the donation process. RESULTS: The decision to donate was a personal choice made before the request by the recipient or transplant service. Spouses verified their support, but indicated that they were not included in the process. No donors felt coerced. The explanation of the procedure was thorough but excessive. Hospital care was good; however, donors admitted being unprepared for the pain and side effects of pain medications. Ongoing incisional discomfort continued beyond 6 weeks and prevented donors from feeling normal. Donors felt conflicted about competing with the "true" patient for healthcare. CONCLUSIONS: Donors were positive about the need and willingness to donate. Sensitivity to the order of the disclosure process is identified.

Improving results in solitary pancreas transplantation with portal-enteric drainage, thymoglobin induction, and tacrolimus/mycophenolate mofetil-based immunosuppression.

Advances in surgical techniques and clinical immunosuppression have led to steadily improving results in pancreas transplantation (PTX). The purpose of this study was to analyze retrospectively the outcomes in patients undergoing solitary PTX with portal-enteric (P-E) drainage and contemporary immunosuppression. From June 1998 through December 2000, we performed 28 solitary PTXs with antibody induction and tacrolimus/mycophenolate mofetil maintenance therapy. The first 13 patients received daclizumab (DAC) induction, while the next 15 received thymoglobulin (rabbit anti-human thymocyte gamma globulin; Thymo) induction. The study group included 13 pancreas alone (PA) and 15 sequential pancreas-after-kidney-transplantations (PAKT). Solitary PTX was performed with P-E drainage in 18 patients and systemic-enteric (S-E) drainage in ten. Patient and pancreas graft survival rates were 96% and 79%, respectively, with a mean follow-up of 22 (range 1-39) months. The 1-year actual death-censored pancreas graft survival rate was 89%. One PAKT patient died with a functioning graft at 1 month; three patients (11%) experienced early graft loss due to thrombosis and were excluded from the immunological analysis, leaving 24 evaluable patients. The incidence of acute rejection was 54%, including 50% in PA and 58% in PAKT recipients ( P=NS). In patients receiving Thymo induction, the rate of acute rejection was slightly lower (43% Thymo vs 70% DAC). Moreover, P-E drainage was associated with a slightly lower rate of acute rejection (44% P-E vs 75% S-E; P=NS). In patients with both Thymo induction and P-E drainage ( n=11), there was a tendency toward less rejection (the incidence of acute rejection was 36%). Two immunological graft losses occurred (one due to non-compliance), both in patients with P-E drainage. Only one patient had a cytomegalovirus (CMV) infection. Event-free survival (no rejection, graft loss, or death) was slightly higher in patients receiving Thymo (47%) than in those on DAC (23%) induction ( P=NS). We can conclude that solitary PTX with P-E drainage and Thymo induction may be associated with improved intermediate-term outcomes and a possible immunological advantage.

Impact of long-term immunosuppressive therapy on psychosocial and physical well being in liver transplant recipients.

To achieve the fullest potential of transplantation, continuing concern for the recipients' quality of life must be a part of the process. Database records of patients who are currently alive and received transplants between 1982 and 1991 were retrospectively analyzed. Recipients were contacted and asked to answer a quality-of-life questionnaire. Of 105 liver transplant recipients, 51 died within 10 years after transplantation; 47 were contacted. Posttransplant complications included hypertension (64%), posttransplant diabetes mellitus (17%), osteopenia (40%), osteoporosis (26%), and heart disease (17%). Most recipients reported all aspects of their life to be average, if not better than their age-matched peers. Although most recipients complained about side effects of immunosuppressive agents, they were all happy to be alive and agreed that their quality of life showed an impressive favorable change to a level exceeding that of the general population. These results suggest that liver transplantation not only improved survival but also quality of life.

Thymoglobulin for induction or rejection therapy in pancreas allograft recipients: a single centre experience.

PURPOSE: To review the safety and efficacy of thymoglobulin in pancreas transplant patients receiving tacrolimus and mycophenolate mofetil. METHODS: Retrospective, single centre analysis of 45 patients transplanted between 1995 and 2000 who received 54 courses of thymoglobulin, including 36 courses in 29 solitary pancreas transplant recipients (16 pancreas alone, 13 pancreas after kidney transplants) and 18 courses in 16 simultaneous kidney-pancreas transplant patients. Thirty-two patients (71%) were primary pancreas transplants, 10 (22%) were second transplants and three (7%) were third transplants. Of the 54 treatment courses, 19 (35%) were for induction, 27 (50%) were for primary rejection and eight (15%) were rescue therapy for rejection. All rejection episodes were biopsy-proven in at least one organ. RESULTS: The median thymoglobulin dose was 1.5 mg/kg/d with a mean of six doses (range 3-10). Dose reduction or interruption was required in 28 courses (52%), most often due to leukopenia (n = 24), fever (n = 2) and thrombocytopenia (n = 2). Thymoglobulin was resumed in all but three patients, two with persistent fever and one with infection. Infectious complications (n = 25) occurred in 17 patients (38%) within 30 days and included bacterial (n = 16), cytomegalovirus (n = 4), polyoma (n = 1), fungal (Candida albicans, n = 1), toxoplasmosis (n = 1) and ehrlichiosis (n = 2). Post-transplant lymphoproliferative disease occurred in two patients (4%) at a mean of 70 d post-thymoglobulin treatment. In the 19 patients that received thymoglobulin induction, one simultaneous kidney-pancreas transplant, two pancreas alone and four pancreas after kidney transplant recipients developed rejection (37% incidence), while all remaining patients followed by surveillance protocol biopsies were rejection-free. In the 35 patients that received thymoglobulin for rejection, reversal occurred in 26 of the patients (74%). Rejection recurred within 30 d in five patients and post-treatment biopsies revealed persistent rejection in three of 20 pancreas and two of eight renal biopsies. After a mean follow-up of 6 months, the actual patient and pancreas graft survival rates were 93% and 71%, respectively. CONCLUSION: Thymoglobulin was effective as induction therapy in high-risk pancreas transplant recipients, and resulted in initial reversal of rejection in 74% of patients. Dose adjustments were required in over half the cases and were usually due to leukopenia. Infections occurring subsequent to thymoglobulin were not uncommon and reflected the immunosuppressive burden of the patient population.

Impact of hepatitis C virus status in pancreas transplantation: a case controlled study.

Available data suggest that hepatitis C virus positive (HCV+) renal transplant patients may be at an increased risk of morbidity and mortality compared with HCV- patients. Limited data are available regarding the impact of HCV status in pancreas transplant patients. We compared the outcomes of 10 HCV+ patients undergoing pancreas transplantation (seven simultaneous kidney-pancreas, one pancreas after kidney, two pancreas alone) between 1/96 and 10/99 with 20 HCV- recipients that were matched for age, race, gender, timing of transplant, type of pancreas transplant, and surgical technique. Length of follow-up was not significantly different between the HCV+ group compared with the HCV- group (24 +/- 14 vs. 20 +/- 13 months; p=0.45). There was a trend toward a higher incidence of all cause mortality in HCV+ recipients compared with HCV- recipients, 30 vs. 10%, respectively (p=0.17). Additionally, the HCV+ recipients had a trend toward a higher incidence of sepsis-related mortality compared with HCV- recipients, 20 vs. 5%, respectively (p=0.19). Renal allograft survival was 50% in the HCV+ group compared with 94% in the HCV- group (p=0.02). Pancreas allograft survival was not significantly different between the groups, 60 vs. 80%, respectively (p=0.24). At 3, 6, 12 months, and end of follow-up, there were no differences in serum creatinine, amylase, C-peptide, or fasting glucose levels. However, there was a significantly higher incidence of proteinuria at last follow-up in the HCV+ recipients with a renal allograft when compared with HCV- recipients, 50 vs. 12.5%, respectively (p=0.05). In order to maintain comparable glycemic control between the groups, there was a significant increase in oral hypoglycemic requirement in HCV+ recipients compared with HCV- recipients, 33 vs. 0%, respectively (p=0.01). These data suggest that HCV+ pancreas transplant patients may be at an increased risk of graft dysfunction and morbidity. Further studies with more patients and longer follow-up are needed to fully define the impact of HCV status on pancreas graft survival and function.