Factors affecting graft survival after adult/child split-liver transplantation: analysis of the UNOS/OPTN data base.

When considering advocacy of split-liver transplantation, it is important to understand whether comparable outcomes can be achieved. The goal of this study was to identify donor and transplant characteristics predictive of comparable outcomes by risk factor analysis. Using the United Network for Organ Sharing/ Organ Procurement and Transplantation Network data base between January 1996 and May 2006, first time adult/child split cases (568 adults, 508 children) were examined. In multivariate analysis, recipient medical condition (hospitalization), status 1 assignment, ABO incompatibility, donor age (>40 years), donor body weight (< or = 40 kg), calculated whole graft volume to recipient body weight ratio (cGRWR < or = 1.5%) and no sharing between centers were significant risk factors in adult recipients. Recipient diagnosis of tumor, dialysis prior to transplant, recipient body weight (< or = 6 kg), donor age (>30 years), donor history of cardiac arrest after declaration of death and cold ischemia time (CIT > 6 h) increased the risk of graft failure in pediatric recipients. The livers from young donors showed comparable outcomes to whole deceased liver transplantation (LT) when other transplant-related risk factors were minimized in adult recipients. Reducing CIT is important to obtain comparable outcomes to living donor LT in pediatric recipients.

Effect modification in liver allografts with prolonged cold ischemic time.

Although prolonged cold ischemia time (PCIT) is generally associated with worse outcomes following liver transplantation, evidence suggests that some recipients and some donors might be more sensitive to PCIT than others. The purpose of this study was to identify factors that predict a higher risk of graft loss after a transplant with PCIT when compared with a similar transplant with average CIT (ACIT). 14 637 recipients reported to United Network for Organ Sharing (UNOS) in the model for end-stage liver disease (MELD) era were studied by interaction term analysis in proportional hazards models. Recipient diabetes, obesity and donor African American (AA) ethnicity were found to significantly amplify the adverse effects of PCIT. Graft loss was 1.85-fold higher in diabetic or obese PCIT recipients compared with diabetic or obese ACIT recipients, (vs. 1.17 for the same comparison in non-diabetic non-obese recipients). Similarly, graft loss was 1.80-fold higher in AA PCIT donors compared with AA ACIT donors, (vs. 1.31 for the same comparison in non-AA donors). Other factors may also exist, but current clinical practices might already mitigate the risks from those factors. As such, we recommend expanding clinical practice to include our findings, but not abandoning current judgment based on factors already perceived to amplify the adverse effects of PCIT.

Liver transplantation: preoperative CT evaluation.

Liver transplantation is a successful therapeutic option for patients with chronic liver disease and liver failure in that 1-year survival is greater than 80%. Orthotopic transplantation is usually performed from a cadaveric or living adult donor. The necessary evaluation of recipients and donors prior to transplantation can be successfully performed with computed tomography (CT). CT is useful in determining clinically relevant information for recipients such as size of the caudate lobe, exclusion of advanced hepatocellular carcinoma and other malignancy, patency of the venous system, presence of perihepatic varices, patency of the celiac artery, exclusion of splenic artery aneurysm, and position of iatrogenic venous shunts. CT in living donors may help to determine clinically relevant information about variant hepatic arterial anatomy, source of the artery to segment IV, intraparenchymal anatomy of the hepatic veins and accessory hepatic veins, trifurcation of the portal vein or hepatic duct, liver volume, and fatty change of the parenchyma. Surgical approaches and the imaging findings that influence management are reviewed.

Donor horseshoe kidneys for transplantation.

BACKGROUND: Experience with donor horseshoe kidneys for transplantation is very limited. Currently, horseshoe kidneys may be underutilized for transplantation because of the greater incidence of vascular anomalies, associated renal anomalies, and predisposition to renal disease. METHODS: In this report, we review five transplantations using horseshoe kidneys: the largest reported institutional experience. In addition, a review of all published cases in the English literature is performed. RESULTS: All five patients underwent successful renal transplantations with a median follow-up of 35 months. One patient lost his kidney from recurrent disease soon after transplantation. CONCLUSION: With appropriate reconstruction of the vessels, careful division of the isthmus, and avoidance of ureteral obstruction, long-term data revealed good graft survival of donor horseshoe kidneys in renal transplantation.

Liver transplantation in patients with severe portopulmonary hypertension treated with preoperative chronic intravenous epoprostenol.

Portopulmonary hypertension (PPHTN) is no longer an absolute contraindication to orthotopic liver transplantation (OLT). The pre-OLT management of patients with PPHTN requires early diagnosis and chronic therapy with intravenous epoprostenol to decrease pulmonary vascular resistance (PVR). Close follow-up is necessary to reassess pulmonary artery pressures (PAPs) and evaluate right ventricular (RV) function. This assists in the optimal timing of OLT. Successful management also necessitates reassessment of pulmonary artery hemodynamics just before OLT, with clearly defined parameters used to determine whether to proceed. Even with the intraoperative and postoperative availability of potent pulmonary vasodilators, clinical management may be suboptimal in reducing PAP. Adequate reduction in PVR and improvement in RV function in response to chronic epoprostenol therapy may facilitate successful OLT. We present a case report and review the limited experience with this treatment.

Measurement of mycophenolate mofetil effect in transplant recipients.

BACKGROUND: Immunosuppression involves the nature of the immunosuppressive agents and individual differences in patient factors. We investigated whether the effect of mycophenolate mofetil (MMF) is measurable using an in vitro measure of immunocompetence and related its effects to cyclosporine (CsA) in vitro. METHODS: Liver or kidney transplant recipients receiving prednisone; CsA or tacrolimus; and MMF, azathioprine (AZA), or neither, were studied. Immunocompetence was assessed by one-way mixed lymphocyte culture using patients' peripheral blood leukocytes (PBL) and three validated stimulators. The effect of immunosuppressive agents added in vitro on normal PBL stimulation by Staphylococcus enterotoxin B was determined by the carboxyfluorescein diacetate succinimidyl ester measurement of division. RESULTS: Patients receiving MMF had an average immunocompetence level of 12+/-23, compared with 39.7+/-65 and 25.5+/-42 for those receiving AZA or neither AZA nor MMF, respectively. Thus, there was an approximately 80% suppression of the response in the MMF group. Assessment of normal cell division revealed that CsA allowed multiple cell generations but suppressed the numbers of cells in each, whereas MMF blocked proliferation into subsequent generations. Addition of clinically relevant levels of mycophenolic acid, the active agent for MMF, added to more moderate levels of CsA, was required to achieve greater than 80% suppression, consistent with the degree of immunocompetence depression measured in patients. CONCLUSIONS: These data provide the novel finding that the effect of MMF treatment on patients is measurable in their PBL as decreased immunocompetence in vitro. The effect of MMF on normal PBL approximates the 80% inhibition that we found in patients. Moreover, the effect of MMF on cell division provides a rationale for the superior effectiveness of regimens including MMF.

Human monocytic ehrlichiosis: an emerging pathogen in transplantation.

BACKGROUND: The spectrum of disease caused by Ehrlichia spp. ranges from asymptomatic to fatal. Awareness and early diagnosis of the infection is paramount because appropriate therapy leads to rapid defervescence and cure. If left untreated, particularly in immunosuppressed patients, ehrlichioses may result in multi-system organ failure and death. METHODS: We report the second case of human monocytic ehrlichiosis (HME) in a liver transplant recipient, and review the literature. RESULTS: The patient presented with fever and headache, had negative cultures, and despite broad-spectrum antimicrobial coverage appeared progressively septic. After eliciting a history of tick exposure we treated the patient empirically with doxycycline. The diagnosis of HME was confirmed by 1) polymerase chain reaction (PCR) for Ehrlichia chaffeensis, 2) acute and convalescent serum titers, and 3) in vitro cultivation of E chaffeensis from peripheral blood. CONCLUSION: Although human ehrlichioses are relatively uncommon, they are emerging as clinically significant arthropod-borne infections. Although epidemiological exposure is responsible for infection, immunosuppression makes patients more likely to succumb to disease. A high index of suspicion and early treatment results in a favorable outcome.

Postoperative morbidity, mortality, costs, and long-term survival in severely obese patients undergoing orthotopic liver transplantation.

OBJECTIVE: Severely obese patients who undergo orthotopic liver transplantation are likely to have higher morbidity, mortality, costs, and a lower long-term survival. METHODS: This case-control study was done at a university hospital. One hundred twenty-one consecutive patients who underwent liver transplantation between 1994 and 1996 were studied. Severe obesity was defined as body mass index (BMI) more than 95th percentile (>32.3 for women and >31.1 for men), and moderate obesity was defined as BMI between 27.3 and 32.3 for women and 27.8 and 31.1 for men. The outcome measures were intraoperative complications, postoperative complications (wound infections, bile leak, vascular complications), length of hospital stay, costs of transplantation, and long-term survival RESULTS: The baseline characteristics, UNOS status, and cause of liver disease at the time of transplantation were similar in severely obese (n = 21, BMI = 37.4+/-4.8 kg/m2), obese (n = 36, BMI 28.7+/-0.9 kg/m2), and nonobese patients (n = 64, BMI 23.8+/-2.5 kg/m2). The intraoperative complications and transfusion requirements were similar in all three groups. The postoperative complications such as respiratory failure (p = 0.009) and systemic vascular complications (p = 0.04) were significantly higher in severely obese patients. The overall perioperative complication rate was 0.61 (39 of 64 patients) in nonobese patients, 0.77 (28 of 36 patients) in obese patients, and 1.43 (30 of 21 patients) in severely obese patients (p = 0.01). Infections were the leading cause of death in all groups accounting for 57-66% of deaths. The length of hospital stay was significantly higher in obese patients. The hospital costs of transplantation were higher ($30,000-$40,000) in severely obese patients than in nonobese patients. The long-term patient survival was similar between the groups (Kaplan-Meier analysis). CONCLUSIONS: Despite higher postoperative complications, severely obese patients have an acceptable long-term survival, which is comparable to nonobese patients. The cost of transplantation is higher among severely obese patients. There was no increased incidence of cardiovascular mortality among severely obese patients during the follow-up period.

Positive effect on T-cell regulatory apoptosis by mycophenolate mofetil.

The regulatory benefit of apoptosis (activation-induced cell death, AICD) in T cells may be impacted by immunosuppressive agents. We examined this for mycophenolate mofetil (MMF) compared with cyclosporine (CYA). Peripheral blood leukocytes (PBL) were stimulated by either Staph enterotoxin B (SEB) or by anti-CD3 plus anti-CD28. Cell division analysis (sequential reduction in carboxyflourescein diacetate succinimidyl ester, CFSE) was used to measure proliferation and determine status of different cell generations. Apoptosis was measured by annexin V staining, and FasL expression by anti-FasL antibody staining, of activated cells using flow cytometry. CSA and mycophenolic acid (MPA, the active agent of MMF) were added in titration in 3-day cultures. We found that CSA caused diminution in apoptosis but MPA increased it with SEB stimulation. The CSA effect on apoptosis was present when a more calcineurin-dependent stimulus. anti-CD3+ anti-CD28, was used but the MPA effect was less, producing a decrease only in the undivided cells. To look more directly at the differential effect on calcineurin-dependent AICD gene induction of the two agents, we measured Fas-L expression with anti-CD-3 + CD28 stimulation, and confirmed that CYA caused a major decrement in appearance of Fas-L, whereas MPA caused a converse accumulation of it. This seems to be explained by the block more distal in cell activation, resulting in a build-up of a precursor in the activation pathways. We conclude that MMF treatment may be rationale as an adjunct to calcineurin inhibitor treatment because of its converse effect on T cell regulatory apoptosis.

Plasmapheresis and intravenous immune globulin provides effective rescue therapy for refractory humoral rejection and allows kidneys to be successfully transplanted into cross-match-positive recipients.

BACKGROUND: Hyperacute rejection (HAR) and acute humoral rejection (AHR) remain recalcitrant conditions without effective treatments, and usually result in graft loss. Plasmapheresis (PP) has been shown to remove HLA- specific antibody (Ab) in many different clinical settings. Intravenous gamma globulin (IVIG) has been used to suppress alloantibody and modulate immune responses. Our hypothesis was that a combination of PP and IVIG could effectively and durably remove donor-specific, anti-HLA antibody (Ab), rescuing patients with established AHR and preemptively desensitizing recipients who had positive crossmatches with a potential live donor. METHODS: The study patients consisted of seven live donor kidney transplant recipients who experienced AHR and had donor-specific Ab (DSA) for one or more mismatched donor HLA antigens. The patients segregated into two groups: three patients were treated for established AHR (rescue group) and four cross-match-positive patients received therapy before transplantation (preemptive group). RESULTS: Using PP/IVIG we have successfully reversed established AHR in three patients. Four patients who were cross-match-positive (3 by flow cytometry and 1 by cytotoxic assay) and had DSA before treatment underwent successful renal transplantation utilizing their live donor. The overall mean creatinine for both treatment groups is 1.4+/-0.8 with a mean follow up of 58+/-40 weeks (range 17-116 weeks). CONCLUSIONS: In this study, we present seven patients for whom the combined therapies of PP/IVIG were successful in reversing AHR mediated by Ab specific for donor HLA antigens. Furthermore, this protocol shows promise for eliminating DSA preemptively among patients with low-titer positive antihuman globulin-enhanced, complement-dependent cytotoxicity (AHG-CDC) cross-matches, allowing the successful transplantation of these patients using a live donor without any cases of HAR.

Successful liver transplantation in a patient with Budd-Chiari syndrome caused by homozygous factor V Leiden.

Budd-Chiari syndrome (BCS) is a rare form of portal hypertension characterized by hepatic venous outflow obstruction. Although hematologic disorders are the most common cause of this syndrome, to date, 30% of the cases have been classified as idiopathic. Resistance to activated protein C caused by factor V Leiden is the most common cause of thrombophilia; its role in the pathogenesis of BCS is now becoming apparent. We report successful liver transplantation in a patient with BCS caused by homozygous factor V Leiden. The patient was administered standard heparin anticoagulation until activated protein C resistance was normalized by the liver allograft. Liver transplantation corrected the thrombophilic state. The patient has excellent graft function, is not on anticoagulation therapy, and has had no recurrent venous thrombosis at 5 months posttransplantation. Activated protein C resistance caused by the factor V Leiden mutation may be responsible for idiopathic cases of BCS. To avoid unnecessary long-term anticoagulation after liver transplantation, factor V Leiden should be considered as a pathogenic factor in BCS. In addition, because of the high prevalence of factor V Leiden in the world population, cadaveric organ donors with a history of venous thrombosis should be screened for activated protein C resistance lest thrombophilia be transmitted to the recipient.

Shorter waiting times for hepatitis C virus seropositive recipients of cadaveric renal allografts from hepatitis C virus seropositive donors.

INTRODUCTION: The purposes of this study were: 1) to analyze the early results of cadaveric renal transplantation from either hepatitis C virus seropositive (HCV+ ) or hepatitis C virus seronegative (HCV-) donors into HCV + recipients; and 2) to determine whether HCV+ patients with end-stage renal disease (ESRD) might benefit from receiving renal allografts from HCV + donors. METHODS: From January 1997 to June 1999, 28 patients with ESRD and HCV infection underwent 29 cadaveric renal transplants. The data were reviewed retrospectively. Nineteen of the renal transplants were performed with allografts obtained from 15 HCV + donors and 10 with allografts obtained from 10 HCV- donors. The median follow-up was 16.2 months, with an average of 15.4+/-2 months. RESULTS: Recipients of HCV + renal allografts had shorter waiting times for transplantation. On average, patients who received a kidney from HCV + donors were transplanted 9+/-3 months after being placed on the transplant list, compared to 29+/-3 months for patients who received a kidney from a HCV- donor. Shorter waiting times were noted in every blood type group. There were no significant differences in rejection episodes, infectious complications, renal function, liver function, graft survival, or patient survival. CONCLUSIONS: The use of renal allografts from HCV + donors for HCV + recipients shortens the waiting time for these patients, with no short-term differences in renal and liver function, graft loss, or patient survival.

Plasmapheresis: an effective therapy for primary allograft nonfunction after liver transplantation.

BACKGROUND: The role of plasmapheresis in liver failure and hepatic coma remains controversial. Also, its use as a salvage strategy for patients with severe allograft dysfunction after liver transplantation has not been defined. This report reviews the use of plasmapheresis in primary hepatic allograft nonfunction (PNF). METHODS: From May of 1997 to October of 1998, five patients underwent plasmapheresis for PNF after other causes of immediate allograft dysfunction were excluded. These patients underwent two to five plasmapheresis procedures during which one plasma volume was removed and replaced with fresh frozen plasma (FFP) or with 50% FFP and 50% albumin. RESULTS: All recipients who underwent plasmapheresis had restoration of liver function. There was one death from pulmonary embolism, for an overall survival rate of 80%. The four surviving patients all had functioning allografts 1 year after liver transplantation. In contrast, during the same period, there were two patients in whom PNF was treated by retransplantation, and both died within 3 months after surgery with functioning allografts. CONCLUSIONS: Plasmapheresis provides an effective treatment option for PNF immediately after liver transplantation and may obviate the need for retransplantation.

Laparoscopic live donor nephrectomy: the recipient.

BACKGROUND: Laparoscopic live donor nephrectomy offers advantages to the donor in terms of decreased pain and shorter recuperation. Heretofore no detailed analysis of the recipient of laparoscopically procured kidneys has been performed. The purpose of this study was to determine whether laparoscopic donor nephrectomy had any deleterious effect on the recipient. METHODS: A retrospective review was conducted of all live donor renal transplantations performed from January 1995 through April 1998. The control group received kidneys procured via a standard flank approach (Open). Rejection was diagnosed histologically. Creatinine clearance was calculated using the Cockroft-Gault formula. RESULTS: A total of 110 patients received kidneys from laparoscopic (Lap) and 48 from open donors. One-year recipient (100% vs. 97.0%) and graft (93.5% vs. 91.1%) survival rates were similar for the Open and Lap groups, respectively. A similar incidence of vascular thrombosis (3.4% vs. 2.1%, P=NS) and ureteral complications (9.1% vs. 6.3%, P=NS) were seen in the Lap and Open groups, respectively. The incidence of acute rejection for the first month was 30.1% for the Lap group and 31.9% for the Open group (P=NS). The rate of decline of serum creatinine level in the early posttransplantation period was initially greater in the Open group, but by postoperative day 4 no significant difference existed. No difference was observed in allograft function long-term. The median length of hospital stay was 7.0 days for both groups. CONCLUSIONS: Laparoscopic live donor nephrectomy does not adversely effect recipient outcome. The previously demonstrated benefits to the donor, and the increased willingness of individuals to undergo live kidney donation, coupled with the acceptable outcomes experienced by recipients of laparoscopically procured kidneys justifies the continued development and adoption of this operation.

Cumulative experience with pediatric living related liver transplantation.

PURPOSE: This study reports the authors' cumulative experience with pediatric living related orthotopic liver transplantation. METHODS: The charts of all patients who received living-related liver transplantation to study complications of transplant surgery, immunosuppression, rejection, and overall survival rate were reviewed retrospectively. RESULTS: Between November 1992 and October 1998, 30 children underwent living-related liver transplantation. Patients were between the ages of 3 months and 7 years of age (mean, 28 months). All received left lateral segmental living-related transplants. At the time of transplant, 14 of 30 patients were listed as United Network of Organ Sharing (UNOS) status 3, 11 were listed as UNOS status 2B, and 5 were listed as UNOS status 1. Indications for transplant included biliary atresia (n = 21), alpha-1-antitrypsin deficiency (n = 2), hepatitis C (n = 2), giant cell hepatitis (n = 2), hepatoblastoma (n = 1), valproic acid toxicity (n = 1), and hemangioendothelioma (n = 1). All donors were parents except for one uncle. There were no major donor complications. Minor complications included wound infection (n = 4), ventral hernia (n = 2), postoperative gastric dysmotility (n = 2), and 1 case of central line-related pneumothorax (n = 1). All but 4 recipients received primary tacrolimus immunosuppressive regimens, and the other 4 underwent conversion from cyclosporine. Initial tacrolimus therapy was begun at 0.15 mg/kg/dose PO/NG every 12 hours. Concomitant immunosuppression included methylprednisolone and mycophenolate mofetil. Fifty-three percent of patients experienced at least 1 episode of rejection, and 27% experienced multiple episodes. Immediate postoperative complications included primary nonfunction (n = 2), vascular thrombosis (n = 3), biliary leaks (n = 3), and infections (n = 17). Two patients (n = 2) required retransplantation. Complications of immunosuppressive therapy included persistent systemic hypertension (n = 6), renal tubular acidosis (n = 3), short-term hyperglycemia (n = 2), neurotoxicity (n = 2), nephrotoxicity (n = 2), food allergies (n = 8), and posttransplant lymphoproliferative disease (n = 4). All patients with PTLD were treated with immunosuppression reduction or withdrawal. Two of 4 had disease progression requiring chemotherapy. The majority of complications were treated with dose adjustments. There were 4 early deaths (13%): 1 of primary nonfunction, 2 of sepsis, and 1 of arrhythmia and renal failure. There was 1 late death of recurrent disease. Twenty-five patients (83%) are alive at 3 months to 6 years post-transplant. CONCLUSION: Living-related orthotopic liver transplantation is an effective intervention for pediatric patients with end-stage disease.

Liver transplantation in infants younger than 1 year of age.

OBJECTIVE: The authors report on experience with liver transplantation for infants younger than 1 year of age. SUMMARY BACKGROUND DATA: Over the last 15 years, orthotopic liver transplant has become the only lifesaving procedure available for infants with end-stage liver disease. Many transplant centers initially required infants to reach a specific weight or age to minimize morbidity and mortality. Size-appropriate infant donors also were uncommon. As a result, many children, in the first few years of life, died of their disease. The availability of reduced-size cadaveric and living-related liver transplants has offered the ability to transplant the young infant with liver failure. METHODS: The authors instituted a program to aggressively transplant infants with liver failure in the first year of life using both cadaveric and living-related liver donors. RESULTS: Between June 1991 and January 1995, 13 infants were transplanted for rapidly progressive liver failure. Infant age ranged from 4 to 11 months (mean, 7.5 months). The cause of liver failure included biliary atresia (11), alpha 1-antitrypsin deficiency (1), and liver failure secondary to echovirus 7 (1). The United Network for Organ Sharing status at the time of transplant ranged from status 4, intensive care unit bound (4 patients); status 3, hospitalized (4 patients); or status 2, failing at home (5 patients). Six patients (46%) received cadaveric whole organ (2) or segmental transplants (4). Seven patients (54%) received left lateral segment living-related transplants from parental donors. After operation, patients received cyclosporine or FK506-based immunosuppression. Three patients (23%) required four retransplants (two cadaveric for primary nonfunction; one living-related for graft thrombosis in the face of fungal infection and bile leak). Postoperative complications included primary nonfunction (15%), rejection (85%), graft vascular thrombosis (15%, two of three revascularized successfully), bacterial and fungal infections (77%), and viral infections (46%). Epstein-Barr virus-associated lymphoproliferative developed in two patients (15%). Intestinal perforation requiring reoperation developed in two patients (15%). Bile leaks requiring reoperation or transhepatic stinting or both developed in three patients (23%). Two patients died in the perioperative period (< 1 month) from a combination of primary nonfunction or graft thrombosis and sepsis. Overall survival was 85%, ranging from 11.0 months to 4.5 years. CONCLUSIONS: Orthotopic liver transplantation in infants younger than 1 year of age poses significant challenges from technical and infectious complications. Despite these barriers, overall patient survival is comparable to that of older children and adults.

Update on vascular access for hemodialysis.

Dialysis as a therapy has become nearly universally available and the ability to provide dialysis and dialysis access over long periods of time has become well established. Unfortunately, technology has yet to provide the perfect dialysis access conduit, one which will not stenose, thrombose, or be prone to infection. Native cephalic vein remains the superior dialysis conduit even 30 years after it was first described. At present, the emphasis in constructing dialysis access must be to attempt to reserve native vein, both in the arm and centrally. The most important decisions remain the ones made at the initiation of dialysis: avoiding subclavian catheters that may lead to subclavian vein stenosis and loss of that extremity for later access; nephrologists making every effort to shelter one extremity for later access formation in the patient who presents with signs of eventual need for dialysis; and if at all possible constructing a native fistula, either forearm or upper arm, which will serve the patient better in the long term, rather than the simpler course of placing a prosthetic graft. Dialysis access planning may need to look 15 to 20 years into the future for the patient who, if not a potential transplant candidate, may remain on dialysis for a very long time. The ability to keep dialysis access functional has improved markedly with the evolution of radiologic methods for thrombolysis and intervention. However, as in other areas of surgery performing the best operation first and avoiding complications is the path that best serves the patient.