Liver transplantation using controlled donation after cardiac death donors: an analysis of a large single-center experience.

The use of donation after cardiac death (DCD) donors may provide a valuable source of organs for liver transplantation. Concerns regarding primary nonfunction (PNF) and intrahepatic biliary stricture (IHBSs) have limited the enthusiasm for their use. A retrospective analysis of 1436 consecutive deceased donor liver transplants performed between December 1998 and October 2006 was conducted. These included 108 DCD liver transplants, which were compared to 1328 transplants performed with organs from donors meeting the criteria for donation after brain death (DBD). The median follow-up was 48 months. The 1-, 3-, and 5-year patient survival and graft survival for DCD donors were 91.5%, 88.1%, and 88.1% and 79.3%, 74.5%, and 71.0%, respectively. The 1-, 3-, and 5-year patient survival and graft survival for DBD donors were 87.3%, 81.1%, and 77.2% and 81.6%, 74.7%, and 69.1%, respectively. Patient survival and graft survival were not significantly different between DCD donors less than 60 years old, DCD donors greater than 60 years old, and DBD donors. Causes of graft loss included IHBSs (n = 9), PNF (n = 4), recurrent hepatitis C virus (n = 4), hepatic artery thrombosis (n = 1), rejection (n = 2), and patient death (n = 13). Contrary to previously published data, excellent long-term patient survival and graft survival can be obtained with DCD allografts, and in our experience, they are equivalent to those obtained from DBD allografts.

Surgical site infection after liver transplantation: risk factors and association with graft loss or death.

BACKGROUND: Risk factors for surgical site infection (SSI) after liver transplantation and outcomes associated with these infections have not been assessed using consensus surveillance and optimal analytic methods. METHODS: A cohort study was performed of patients undergoing first liver transplantation at Mayo Clinic, Jacksonville, Florida, in 2003 and 2004. SSIs were identified by definitions and methods of the National Nosocomial Infections Surveillance System. Measures of known or suspected risk factors for SSI, graft loss, or death were collected on all patients. Associations of SSI with these factors and also with the primary composite endpoint of graft loss or death within 1 year of liver transplantation were examined using Cox proportional hazards models; relative risks (RRs) were estimated along with 95% confidence intervals (CIs). RESULTS: Of 370 patients, 66 (18%) had SSI and 57 (15%) died or sustained graft loss within 1 year after liver transplantation. Donor liver mass-to-recipient body mass ratio of less than 0.01 (RR 2.56; 95% CI 1.17-5.62; P=0.019) and increased operative time (RR 1.19 [1-hr increase]; 95% CI 1.03-1.37; P=0.018) were associated with increased SSI risk. SSI was associated with increased risk of death or graft loss within the first year after liver transplantation (RR 3.06; 95% CI 1.66-5.64; P<0.001). CONCLUSION: SSI is associated with increased risk of death or graft loss during the first year after liver transplantation. Increased operative time and decreased donor liver-to-recipient body mass ratio showed evidence of association with SSI.

Long-term outcomes of donation after cardiac death liver allografts from a single center.

Organ shortage continues to be a major challenge in transplantation. Recent experience with controlled non-heart-beating or donation after cardiac death (DCD) are encouraging. However, long-term outcomes of DCD liver allografts are limited. In this study, we present outcomes of 19 DCD liver allografts with follow-up >4.5 years. During 1998-2001, 19 (4.1%) liver transplants (LT) with DCD allografts were performed at our center. Conventional heart-beating donors included 234 standard criteria donors (SCD) and 214 extended criteria donors (ECD). We found that DCD allografts had equivalent rates of primary non-function and biliary complications as compared with SCD and ECD. The overall one-, two-, and five-yr DCD graft and patient survival was 73.7%, 68.4%, and 63.2%, and 89.5%, 89.5%, and 89.5%, respectively. DCD graft survival was similar to graft survival of SCD and ECD in non hepatitis C virus (HCV) recipients (p > 0.370). In contrast, DCD graft survival was significantly reduced in HCV recipients (p = 0.007). In conclusion, DCD liver allografts are durable and have acceptable long-term outcomes. Further research is required to assess the impact of HCV on DCD allograft survival.

Pancreas transplant venous thrombosis: role of endovascular interventions for graft salvage.

Venous thrombosis of pancreas transplant allografts often leads to graft loss. We evaluated the efficacy of emergent endovascular techniques to salvage thrombosed pancreatic allografts in a series of six patients. Of the 76 pancreas transplants performed between 2002 and 2006, six patients were diagnosed with venous thrombosis on MRI between 2 and 28 days posttransplant (mean, 9 days). Five patients were systemic-enteric (donor portal vein anastomosis to recipient iliac vein) and one patient was portal-enteric (donor portal vein anastomosis to recipient superior mesenteric vein). Conventional venography confirmed the diagnosis of venous thrombosis in all patients. One patient was treated with catheter-directed venous thrombolysis and balloon thrombectomy. Another patient was treated with rheolytic thrombectomy alone. The remaining four patients were treated with a combination of these mechanical and thrombolytic techniques. Completion venography revealed >50% clot reduction and resumption of venous drainage in all patients. One patient required additional intervention 16 days later for recurrent thrombosis. Two patients required metal stent placement for anastomotic stenoses or kinks. One patient required pancreatectomy 36 h after attempted salvage secondary to a major hemorrhage and graft necrosis. Two patients recovered pancreatic function initially but lost graft function at 8 and 14 months, respectively, from severe chronic rejection. Patient survival was 100%, long-term graft survival was 50%, rethrombosis rate was 16.6%, and graft loss from rejection was 33%. In conclusion, early recognition and treatment of venous thrombosis after pancreas transplantation has acceptable morbidity and no mortality using short-term endovascular pharmacomechanical therapy.

Excellent renal allograft survival in donor-specific antibody positive transplant patients-role of intravenous immunoglobulin and rabbit antithymocyte globulin.

BACKGROUND: Timely transplantation of sensitized kidney recipients remains a challenge. Patients with a complement-dependent cytotoxicity negative and flow cytometry (FC) positive crossmatch carry increased risk of antibody-mediated rejection and thus graft loss. Solid phase assays are available to confirm donor specificity for antibody identified by FC crossmatch. Treatment using induction therapy with rabbit antithymocyte globulin (RATG) and intravenous immunoglobulin (IVIG) may allow successful transplant of these high-risk patients. METHODS: A retrospective study of 264 consecutive patients after exclusions yielded 94 complement-dependent cytotoxicity anti-human globulin crossmatch-negative patients, including group 1: 58 primary transplants with panel-reactive antibody (PRA) less than 20%, group 2: 16 retransplants and PRA more than 20% who were FC crossmatch-negative, and group 3: 20 retransplants and PRA more than 20% who were FC crossmatch-positive. All were treated with RATG induction and maintenance therapy with tacrolimus, mycophenolate mofetil, and corticosteroids. Only group 3 received IVIG at 500 mg/kg daily in three doses. RESULTS: Eighteen of 20 patients in group 3 had donor-specific antibody identified by solid phase assay. Cellular- and antibody-mediated rejections were statistically higher in group 3. Two-year serum creatinine and glomerular filtration rate along with 3-year patient and graft survival were comparable between the groups. CONCLUSIONS: Sensitized patients with positive FC crossmatch and donor-specific antibody identified by solid phase assays can be successfully transplanted using standard RATG induction, IVIG, and maintenance immunosuppression with equal renal function and graft survival to immunologically lower risk recipients. Given these results, this patient group should not be excluded from transplantation based on antibody specificities determined by virtual crossmatch techniques.

Peritonitis after liver transplantation: Incidence, risk factors, microbiology profiles, and outcome.

Peritonitis occurring after liver transplantation (PLT) has been poorly characterized to date. The aims of this study were to define the incidence, risk factors, microbiology profiles, and outcome of nonlocalized PLT. This was a retrospective study of 950 cadaveric liver transplantation (LT) procedures in 837 patients, followed for a mean of 1,086 days (range, 104-2,483 days) after LT. PLT was defined as the presence of at least one positive ascitic fluid culture after LT. There were 108 PLT episodes in 91 patients occurring at a median of 14 days (range, 1-102 days) after LT. Significant risk factors associated with the development of PLT by multivariate analysis included pre-LT model for end-stage liver disease score, duration of LT surgery, Roux-en-Y biliary anastomosis, and renal replacement therapy after LT. Biliary complications, intra-abdominal bleeding, and bowel leak/perforation were associated with 34.3%, 26.9%, and 18.5% of episodes, respectively. Multiple organisms, gram-positive cocci, fungus, and multidrug-resistant bacteria were isolated in 61.1%, 92.6%, 25.9%, and 76.9% of ascitic fluid cultures, respectively. The 28 fungal PLT episodes were associated with bowel leak/perforation and polymicrobial peritonitis. Patients who developed PLT after their first LT had a significantly greater risk of graft loss or mortality compared to unaffected patients. Parameters significantly associated with these adverse outcomes by multivariate analysis were recipient age at LT and bowel leak or perforation after LT. In conclusion, PLT is a serious infectious complication of LT, associated with significant intra-abdominal pathology and reduced recipient and graft survival.

Donor age affects fibrosis progression and graft survival after liver transplantation for hepatitis C.

BACKGROUND: The use of liver allografts from an older donor (OD) (age>50 years) is a widespread strategy to manage the disparity between supply and demand of organs for liver transplantation. This study determines the effect of OD allografts on fibrosis progression and graft survival after liver transplantation in patients with and without infection caused by hepatitis C virus (HCV). METHODS: All patients undergoing liver transplantation at our center from March 1998 to December 2001 were analyzed. Protocol liver biopsies were performed at 1, 16, and 52 weeks after transplantation and yearly thereafter. One liver pathologist scored all biopsy specimens for modified hepatic activity index (0-18) and fibrosis (0-6). RESULTS: A total of 402 patients (167 with HCV and 235 without HCV) underwent liver transplantation during the study period. Among patients with HCV, baseline characteristics of OD recipients were similar to younger donor (YD) (age<50 years) recipients. In patients with HCV, graft survival was shorter in OD graft recipients than in YD recipients (P<0.001). In patients without HCV, graft survival was independent of donor age. In patients with HCV, a fibrosis score of 3 or greater was present in 17% of OD recipients at 4 months and in 26% at 12 months after transplantation, compared with 8% of YD recipients at 4 months and 13% at 12 months (P<0.001). CONCLUSIONS: Liver transplantation with OD grafts is associated with rapid progression of fibrosis and decreased graft survival in patients with HCV, but not in patients without HCV. OD grafts should be considered preferentially for patients without HCV.

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.

Long-term experience with simultaneous kidney-pancreas transplantation with portal-enteric drainage and tacrolimus/mycophenolate mofetil-based immunosuppression.

UNLABELLED: Refinements in surgical techniques and advances in clinical immunosuppression have led to steadily improving results in pancreas transplantation (PTX). Although there is renewed interest in enteric exocrine drainage, most PTXs are performed with systemic venous delivery of insulin. To improve the physiology of PTX, we developed a novel technique of portal venous delivery of insulin and enteric drainage of the exocrine secretions (portal-enteric [P-E]). The purpose of the study was to analyse outcomes in patients undergoing PTX with P-E drainage and contemporary immunosuppression. MATERIALS AND METHODS: From January 1997 through September 2002, we performed 67 primary simultaneous kidney-PTXs (SKPT) with P-E drainage. Maintenance immunosuppression consisted of tacrolimus (TAC), mycophenolate mofetil (MMF) and steroids. No antibody induction therapy occurred in 33 patients (49%) with the remainder receiving daclizumab (n = 15), basiliximab (n = 2), or thymoglobulin (n = 14) induction therapy. The patient group included 38 males and 29 females with a mean age of 39.7 year (range 23-58) and a mean duration of pretransplant diabetes of 24.5 year (9-46). Fourteen patients (21%) were African-American. RESULTS: The mean waiting time for SKPT was 3.3 months (range 0.1-10). Mean kidney and pancreas cold ischaemia times were 15.1 and 15.4 h, respectively. Patient, kidney and pancreas graft survival rates were 97%, 92.5% and 82%, respectively, with a mean follow-up of 20 months (range 1-56). Two deaths (one sepsis, one cardiac event) occurred at 1 month after SKPT; both patients died with functioning grafts (DWFG). Three patients (4.5%) had delayed renal allograft function and received temporary dialysis after SKPT. Five kidney graft losses occurred (two DWFG, one thrombosis, two chronic rejection). All but four patients (6%) had immediate PTX function. A total of 12 pancreas graft losses occurred (two DWFG, five thrombosis, five chronic rejection). The incidence of acute rejection was 28%, but no grafts were lost due to isolated acute rejection. The incidence of major infection was 51%, but only five patients (7.5%) developed cytomegalovirus infection. A total of 19 patients (28%) underwent early relaparotomy within 3 months of SKPT. The composite endpoint of no rejection, graft loss, or mortality was attained by 63% of patients. At present, 58 patients (87%) are both dialysis and insulin-independent (including four retransplants). CONCLUSION: These findings suggest that SKPT with P-E drainage and contemporary immunosuppression may result in excellent intermediate-term outcomes.

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.