Risk Factors for Posttransplant Lymphoproliferative Disorder in Pediatric Liver Transplant Recipients With Cytomegalovirus Antigenemia

Epstein-Barr virus (EBV) infections, associated with posttransplant lymphoproliferative disorder (PTLD) are known to develop in cytomegalovirus (CMV)-infected transplant recipients due to the indirect effects of CMV. This study evaluated risk factors for PTLD among pediatric liver transplant recipients with CMV infections. We reviewed the medical records of 119 patients ≤18 years old who underwent liver transplantation between September 1996 and April 2009. Sixty-six subjects (55.5%) displayed CMV antigenemia during the study period; 15 (12.6%) developed PTLD. Of these, 10 developed PTLD after CMV antigenemia. The other patients (n = 5) were excluded due to negative CMV antigenemia. The incidence of PTLD influenced by CMV infection was not significantly different from the incidence of PTLD without underlying CMV (P = .258). There were no differences in age, gender, antiviral prophylaxis, type of liver transplantation, or acute rejection episodes in the incidence of between patients with versus without PTLD. EBV but not CMV high-risk groups were a predictor for the development of PTLD (P = .035). CMV syndrome, tissue-invasive CMV disease, and CMV peak titer were not associated with an increased risk of PTLD. The primary risk factor for PTLD was EBV high-risk patients (donor positive/recipient negative). CMV disease was not associated with PTLD in pediatric liver transplant recipients with CMV infections.     

The influence of acute rejection on long-term renal allograft survival: a comparison of living and cadaveric donor transplantation

BACKGROUND: We investigated whether recipients of living donor grafts who suffer an acute rejection progress to graft loss because of chronic rejection at a slower rate than recipients of cadaveric grafts. METHODS: A retrospective review was made of 296 renal transplantations performed at Mount Sinai Hospital. Only grafts functioning for at least 3 months were included in this analysis. Demographic variables of donor and recipient age, race, sex, and serum creatinine at 3 months after transplantation were compared between groups. RESULTS: Among the acute rejection-free cohort, the estimated 5-year graft survival was 90% for those receiving transplants from living relatives and 88% for those receiving cadaveric transplants (P=0.76). However, in grafts with early acute rejection, the 5-year survival was 40% for cadaveric recipients compared with 73% for living related graft recipients (P<0.014). Using the proportional hazards model, cadaveric donor source, older donor age, African American recipient race, and elevated 3-month serum creatinine were independent predictors of long-term graft loss caused by chronic rejection. The severity of acute rejection and recipient age had no impact on the risk of graft loss because of chronic rejection. CONCLUSION: These data indicate that the benefit of living related transplantation results from the fact that a living related graft progresses from acute to chronic rejection at a slower rate than a cadaveric graft. Furthermore, a cadaveric graft that is free of acute rejection 3 months after transplantation has an equal likelihood of functioning at 5 years as that of a graft from a living related donor.     

Risk Factors for Rejection and Infection in Pediatric Liver Transplantation

Rejection and infection are important adverse events after pediatric liver transplantation, not previously subject to concurrent risk analysis. Of 2291 children (<18 years), rejection occurred at least once in 46%, serious bacterial/fungal or viral infections in 52%. Infection caused more deaths than rejection (5.5% vs. 0.6% of patients, p < 0.001). Early rejection (<6 month) did not contribute to mortality or graft failure. Recurrent/chronic rejection was a risk in graft failure, but led to retransplant in only 1.6% of first grafts. Multivariate predictors of bacterial/fungal infection included recipient age (highest in infants), race, donor organ variants, bilirubin, anhepatic time, cyclosporin (vs. tacrolimus) and era of transplant (before 2002 vs. after 2002); serious viral infection predictors included donor organ variants, rejection, Epstein-Barr Virus (EBV) naivety and era; for rejection, predictors included age (lowest in infants), primary diagnosis, donor-recipient blood type mismatch, the use of cyclosporin (vs. tacrolimus), no induction and era. In pediatric liver transplantation, infection risk far exceeds that of rejection, which causes limited harm to the patient or graft, particularly in infants. Aggressive infection control, attention to modifiable factors such as pretransplant nutrition and donor organ options and rigorous age-specific review of the risk/benefit of choice and intensity of immunosuppressive regimes is warranted.     

Long-term survival and late graft loss in pediatric liver transplant recipients—a 15-year single-center experience

Increasing numbers of children undergo successful liver transplantation. Limited data exist on long-term survival and late graft loss. Survival and graft loss were studied in 376 primary liver graft recipients who survived more than 3 months after transplantation (80.5% of all primary graft recipients). Patient records were reviewed retrospectively for causes of graft loss. Risk factors were identified by analyzing graft, recipient, and posttransplant variables using multivariate Cox regression. One-, 5-, and 10-year actuarial graft survival rates in the study population were 94.6%, 87.3%, and 86.3%, respectively. Corresponding patient survival rates were 95.7%, 91.4%, and 90.4%. Forty-seven (12.5%) grafts were lost subsequently, 15 by patient death with preserved graft function. Survival rate after late retransplantation was 63.3%. Causes of late graft loss were infection (21.2%), posttransplant lymphoproliferative disease (PTLD, 21.2%), chronic rejection (17%), biliary complications (14.8%), and recurrence of malignant disease (8.5%). Independent risk factors for late graft loss and patient death included liver malignancy as primary disease, steroid resistant rejection, and PTLD. Graft loss rate was significantly increased for reduced-size grafts. Patients undergoing transplantation after 1991 and recipients of full-size grafts were more likely to survive. In conclusion, the long-term outcome for pediatric primary liver graft recipients surviving the early postoperative period is excellent except for patients with liver malignancy. There is no increased risk of late graft loss with the use of split or living related donor grafts. Technical complications are only a minor factor in late graft loss, but complications related to immunosuppression and infection remain a major hazard and must be addressed. (Liver Transpl 2002;8:615-622.)     

Prospective longitudinal analysis of quantitative Epstein-Barr virus polymerase chain reaction in pediatric liver transplant recipients

BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) remains a significant cause of morbidity and mortality in pediatric liver transplant recipients. Epstein-Barr Virus (EBV) mismatch associated with more prevalent use of split-liver, reduced size, and living-related transplants has increased the risk of primary EBV infection and subsequent PTLD. Early identification of EBV viremia may reduce the risk of PTLD, because it allows for early adjustment of immunosuppression and antiviral therapy. METHODS: EBV viral load was measured monthly by quantitative competitive polymerase chain reactions in three pediatric liver transplant recipients. RESULTS: Onset of EBV viremia was documented in one recipient. Established EBV viremia was followed in the other two recipients (one with chronic rejection and one with PTLD) who were initially tested once monitoring was initiated in our program. CONCLUSIONS: EBV quantitative competitive polymerase chain reactions may represent a promising way to follow EBV viral load and potentially prevent the development of PTLD.     

Pediatric renal transplantation under FK-506 immunosuppression.

Renal transplantation (11 cadaveric and 1 living-related donor) was performed in 12 pediatric recipients (mean age 10.8 years) under FK-506 immunosuppression in combination with prednisone therapy. At a mean followup of 6.1 months, patient and graft survival rates were 100% and 92%, respectively. The only graft loss was due to the recurrent hemolytic uremic syndrome 4 days after transplantation. In the functioning grafts the mean serum creatinine is 1.59 +/- 1.27 mg./dl. and the mean blood urea nitrogen is 36.3 +/- 24.6 mg./dl. Three patients take no prednisone, 5 are receiving 0.15 to 0.25 mg./kg. per day and 3 are taking 0.35 to 0.5 mg./kg. per day. There was a total of 8 rejection episodes in 5 patients. All rejection episodes were successfully reversed. Complications of transplantation included an episode of seizures in 1 patient, cytomegalovirus infection in 1 and steroid-induced diabetes mellitus in 1. Since pediatric transplant recipients are a group in whom the reduction or elimination of steroids is highly desirable, FK-506 immunosuppression may be particularly suited for use in this population.     

Early graft function after pediatric liver transplantation: comparison between in situ split liver grafts and living-related liver grafts.

BACKGROUND: The systematic application of living-related and cadaveric, in situ split-liver transplantation has helped to alleviate the critical shortage of suitable-sized, pediatric donors. Undoubtedly, both techniques are beneficial and advantageous; however, the superiority of either graft source has not been demonstrated directly. Because of the potential living-donor risks, we reserve the living donor as the last graft option for pediatric recipients awaiting liver transplantation. Inasmuch as no direct comparison between these two graft types has been performed, we sought to perform a comparative analysis of the functional outcomes of left lateral segmental grafts procured from these donor sources to determine whether differences do exist. METHODS: A retrospective analysis of all liver transplants performed at a single institution between February 1984 and January 1999 was undertaken. Only pediatric (<18 years) recipients of left lateral segmental grafts procured from either living-related (LRD) or cadaveric, in situ split-liver (SLD) donors were included. A detailed analysis of preoperative, intraoperative, and postoperative variables was undertaken. Survival was estimated using the Kaplan-Meier method, and comparison of variables between groups was undertaken using the t test of Wilcoxon rank sum test. RESULTS: There were no significant differences in the preoperative variables between the 39 recipients of SLD grafts and 34 recipients of LRD grafts. The donors did differ significantly in mean age, ABO blood group matching, and preoperative liver function testing. Postoperative liver function testing revealed significant early differences in aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, prothrombin time, and alkaline phosphatase, with grafts from LRD performing better than those from SLD. SLD grafts also had significantly longer ischemia times and a higher incidence of graft loss owing to primary nonfunction and technical complications (9 vs. 2, P<0.05). However, six of these graft losses in the SLD group were because of technical or immunologic causes, which, theoretically, should not differ between the two groups. Furthermore, these graft losses did not negatively impact early patient survival as most patients were successfully rescued with retransplantation (30-day actuarial survival, 97.1% SLD vs. 94.1% LRD, P=0.745). In the surviving grafts, the early differences in liver function variables normalized. CONCLUSIONS: Inherent differences in both donor sources exist and account for differences seen in preoperative and intraoperative variables. Segmental grafts from LRD clearly performed better in the first week after transplantation as demonstrated by lower liver function variables and less graft loss to primary nonfunction. However, the intermediate function (7-30 days) of both grafts did not differ, and the early graft losses did not translate into patient death. Although minimal living-donor morbidity was seen in this series, the use of this donor type still carries a finite risk. We therefore will continue to use SLD as the primary graft source for pediatric patients awaiting liver transplantation.     

Effect of donor age on the outcome of living-related kidney transplantation

The study compared the results of kidney transplantation from living-related donors older and younger than 60 years. The 273 kidney graft recipients were divided into group 1 (115 recipients of older grafts) and group 2 (158 recipients of younger grafts). The frequency of acute rejection (AR) episodes was similar in both groups but slow graft function occurred more frequently in group 1. The frequency of chronic renal allograft dysfunction in the first post-transplant year was significantly higher in group 1 than in group 2. Patient and graft survival was significantly worse in group 1. Risk factors for graft loss were the difference between donor and recipient age and AR. Donor age and graft function were risk factors for patient death. Although kidneys from older donors provide a statistically poorer transplant outcome, they are clinically acceptable, especially when waiting time is prolonged and access to dialysis limited.     

Maternal grafts protect daughter recipients from acute cellular rejection after pediatric living donor liver transplantation for biliary atresia

Some studies have found that gender mismatch between donors and recipients are related to poor graft prognosis after liver transplantation. However, few studies have investigated the impact of gender mismatch on acute cellular rejection (ACR) in pediatric living donor liver transplantation (LDLT). This retrospective study investigated the clinical significance of these factors in ACR after pediatric LDLT. Between November 2001 and February 2012, 114 LDLTs were performed for recipients with biliary atresia (BA) using parental grafts. We performed univariate and multivariate analyses to identify the factors associated with ACR. The donor–recipient classifications included mother donor to daughter recipient (MD; n = 43), mother to son (n = 18), father to daughter (FD; n = 33), and father to son (n = 20) groups. The overall incidence rate of ACR in the recipients was 36.8%. Multivariate analysis showed that gender mismatch alone was an independent risk factor for ACR (P = 0.012). The FD group had a higher incidence of ACR than the MD group (P = 0.002). In LDLT, paternal grafts with gender mismatch were associated with a higher increased incidence of ACR than maternal grafts with gender match. Our findings support the possibility that maternal antigens may have an important clinical impact on graft tolerance in LDLT for patients with BA.     

Advances in pediatric liver and intestinal transplantation

BACKGROUND: Significant progress has been made with liver and intestinal transplantation in pediatric patients. Shortage of whole-organ cadaveric grafts has resulted in a high mortality rate for children awaiting transplantation. New surgical procedures such as split-liver transplantation and living-related liver transplantation have evolved over the last decade to maximize donor utilization in pediatric patients. METHODS: In this article we review the current indications and contraindications for liver and intestinal transplantation in children, the surgical innovations to expand an exceedingly small cadaveric liver pool, postoperative management, and the impact on patient and graft survival. RESULTS: Reduced-size liver transplantation provides children with much needed small grafts; however, split-liver transplantation may eliminate the need for reduced-size and living-related liver transplantation except in urgent situations. CONCLUSION: Liver transplantation is a durable procedure that provides excellent long-term survival. The use of living-related and split-liver transplantation has dramatically reduced the waiting periods for children and improved survival. In the past decade significant progress has been made with intestinal transplantation owing to improvements in surgical technique, immunosuppressive agents, and early identification and treatment of postoperative complications.     

Cytomegalovirus as a risk factor in living-related renal transplantation. A prospective study.

Forty-four living-related donor kidney (LRD) recipients (19 HLA-identical and 25 haploidentical) were followed prospectively to determine the posttransplant incidence and sequelae of cytomegalovirus (CMV) infection as they relate to the CMV status of recipients and donors. CMV titers were measured in all patients before transplantation by an immunofluorescent assay (IFA). Recipients similarly had CMV titers measured at selected intervals after transplant and during febrile episodes. Appropriate viral cultures were simultaneously performed. Laboratory evidence of infection was correlated with symptoms and signs of active CMV disease. Mean follow-up period was 20 +/- 12 months with a range of 3-51 months. Three patients were excluded due to early acute rejection resulting in graft loss. Twenty-eight of 41 donors (68%) and 22 of 41 recipients (54%) had positive CMV titers before transplantation. Six of 41 recipients (15%) subsequently developed clinical and laboratory evidence of CMV infection: three of 19 seronegative recipients and three of 22 seropositive recipients. All six patients received kidneys from seropositive donors. Four patients had severe CMV disease (2 seronegative, 2 seropositive), whereas two patients had leukopenia and fever only. Two patients with severe CMV infections subsequently lost their grafts due to unrelated causes. Overall, actual patient and graft survival of the entire group is 95% and 82%, respectively. In conclusion, individuals who receive LRD kidneys from seronegative individuals are unlikely to develop CMV infection, and transplantation of seropositive LRD kidneys may be associated with transmission of CMV in susceptible recipients regardless of their serologic status. With appropriate management of CMV illness in the posttransplant period, LRD kidney donation is safe and efficacious and should not be discouraged on the basis of pretransplant CMV serology in any donor-recipient pairing.     

Outcome of renal transplantation in children less than two years of age.

Twenty-two renal transplants were performed in 21 children less than two years of age at Children's Hospital. Fourteen were from living related donors and eight were from cadaveric donors. The five year patient and graft survivals of these recipients were compared to all other pediatric recipients between two and 18 years of age who received renal transplants over the same time period. Five year graft survival for recipients less than two years of age was 86% following living-related donor transplantation and 38% following cadaver donor transplantation. Older pediatric recipients aged between two and 18 years had a five year graft survival of 73% following living-related donor renal transplantation, which was similar to that for recipients less than two years of age. Although older cadaveric recipients had a comparable five year graft survival to younger recipients, at 42%, the patterns of graft loss were different. Graft failures in young recipients occurred within the first seven months post-transplant, whereas the older recipient's grafts failed more gradually. Actuarial five-year patient survival in recipients less than two years of age was 86% following living-related donor renal transplantation and 70% following cadaver-donor renal transplantation. Recipients less than two years of age had a poorer patient survival than older recipients following both living-related donor renal transplantation (P = 0.06) and cadaver-donor renal transplantation (P less than 0.05). These findings suggest that the graft survival of living-related donor renal transplantation in recipients less than two years of age is better than that of cadaver-donor renal transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical study of 18 pediatric cadaveric renal transplantations: organ sharing in pediatric renal transplantation after enforcement of the organ transplant law in Japan

Renal transplantation is considered to be the optimal replacement therapy for children with end-stage renal disease. However, the number of pediatric renal transplants in Japan is much lower than in the USA and/or Europe. Since October 1997, pediatric(< 15 years) recipients are given priority over adult recipients for organ sharing, only if one or two HLA-DR antigen(s) are matched between the recipient and pediatric(< 15 years) donor. However, the number of pediatric transplants is not increasing. One hundred and twenty-four pediatric renal transplantations were performed in Tokyo Women's Medical University between 1983 and 1999, of which 18(14.5%) were cadaveric transplants and the others (106, 85.5%) were living-related transplants. We examined 18 pediatric cadaveric renal transplantations. Seven patients received their graft from pediatric donors less than 15 years of age and 11 from adult donors. The mean age at transplantation was 13.2 years (range 4.5-18.7 years). Major etiologies of renal disease are hereditary renal disease(38.8%), chronic glomerulonephritis(33.3%), and focal segmental glomerulosclerosis[FSGS] (16.7%). Zero matches in HLA-DR locus were observed in 72.2%. Patient survival rate was 100%. Graft survival rates at 1 and 5 years after transplantation were 83% and 64% successively. There was no significant difference between the graft survival of cadaveric and living-related transplantation at 1 and 5 years. All 5 patients who received their graft between 1994 and 1998 have maintained normal graft function. Causes of their graft loss were chronic rejection in 3, recurrence of FSGS in 2, primary non-function in 1, and graft thrombosis in 1. Donor age and HLA-DR mismatching did not affect the outcome. We propose that pediatric renal grafts should be provided to children with priority, regardless of their HLA-A, B and HLA-DR matching.     

Safety of Blood Group A2-to-O Liver Transplantation: An Analysis of the United Network of Organ Sharing Database

BACKGROUND: ABO-incompatible organ transplantation typically induces hyperacute rejection. A2-to-O liver transplantations have been successful. This study compared overall and graft survival in O recipients of A2 and O grafts based on Organ Procurement and Transplantation Network data. METHODS: Scientific Registry of Transplant Recipients data were used. The first A2-to-O liver transplantation was entered on March 11, 1990; all previous transplantations were excluded. Between March 11, 1990, and September 3, 2010, 43,335 O recipients underwent transplanation, of whom 358 received A2 grafts. RESULTS: There were no significant differences in age, sex, and race between the groups. Recipients of A2 grafts versus O grafts were significantly more likely to be hospitalized at transplantation (45% vs. 38%, P≤0.05) and to have a higher mean (SD) model for end-stage liver disease score (24 [11] vs. 22 [10], P≤0.05). 10% of A2 recipients and 9% of O recipients underwent retransplantation. No significant differences existed in rejection during the transplantation admission and at 12 months: 7% versus 6% and 20% versus 22% for A2 recipients and O recipients, respectively; and there were no significant differences in contributing factors to graft failure or cause of death. At 5 years, overall survival of A2 and O graft recipients was 77% and 74%, respectively (log rank=0.71). At 5 years, graft survival was 66% in both groups (log rank=0.52). Donor blood group was insignificant on Cox regression for overall and graft survival. CONCLUSIONS: Using Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients data, we present the largest series of A2-to-O liver transplantations and conclude this mismatch option to be safe with similar overall and graft survival. This opens possibilities to further meet the demands of a shrinking organ supply, especially with regard to expanding living-donor options.     

Risk factors for post-transplant lymphoproliferative disease in patients with cystic fibrosis

The objective of this study was to retrospectively analyze risk factors associated with post-transplant lymphoproliferative disease (PTLD) in a cohort of 112 lung transplant recipients with cystic fibrosis (CF). Prior to transplantation, patients were tested for Epstein-Barr virus (EBV), human herpesvirus (HHV types 1, 2, 3, 6, and 8), herpes zoster virus, and cytomegalovirus (CMV) serologies. PTLD diagnosis was established based on increased EBV viral charge plus clinical/radiographic findings and confirmed by biopsy. Negative EBV and HHV serologies at the time of lung transplantation (LTx) were significant risk factors associated with development of PTLD in patients with CF in the univariate logistic regression analysis (p < 0.05) and also in the multivariate analysis (odds ratio of 77.5 and 12.5, respectively). CMV serology, CMV mismatch, acute rejection in the first three months following LTx, HLA-A3 antigen expression, and female gender did not affect PTLD. Our study confirmed the presence of a strong association between negative EBV serology at the time of LTx and PTLD and suggested an independent effect of negative HHV serology on PTLD.     

Chronic rejection in primary renal allograft recipients under cyclosporine-prednisone immunosuppressive therapy

Although the introduction of cyclosporine-prednisone immunosuppression has improved early renal graft survival, chronic rejection remains a major cause of longterm graft dysfunction. This study retrospectively examined 69 cases of chronic rejection among 643 primary renal allograft recipients treated with cyclosporine-prednisone immunosuppression from July 1981 to October 1989. Chronic rejection was defined as a rejection episode diagnosed greater than 90 days posttransplantation with characteristics of progressive nonacute renal function deterioration, confirmed, in most cases, by renal biopsy. This group was compared with an equal-sized matched cohort. Among cadaveric recipients, 61 of 456 patients (13.4%) displayed chronic rejection, whereas among living-related recipients, 8 of 187 patients (4.3%) developed chronic rejection. The average time from the date of transplantation to diagnosis of chronic rejection was 15 +/- 14 months. One- and three-year graft survivals following diagnosis of chronic rejection were 51% (30/59) and 25% (13/51), respectively, compared with the cohort one- and three-year graft survivals of 98% (58/59) and 86% (32/37) at similar periods posttransplantation. HLA mismatch, PRA status, blood transfusion history, lipid levels, cyclosporine trough levels, incidence of prior acute rejection, and initial graft dysfunction were not significantly different between the chronic rejection group and the matched cohort. Hypertension and proteinuria were significantly associated with chronic rejection (P less than 0.001). Of 58 biopsies performed, findings solely consistent with chronic rejection were observed in 9 cases (15%) and "acute upon chronic" rejection in 49 cases (83%). Treatment of acute concomitants improved the renal function in 43% (27/63) by the time of hospital discharge. Nonetheless, at 12 months the incidence of improved renal function eroded to 22% (13/59), suggesting that the benefit was relatively short-lived. Although the overall incidence of chronic rejection in this group of cyclosporine-prednisone-treated patients was lower than previous azathioprine-prednisone cohorts, the clinical presentation and progression of chronic rejection was similar. Additionally, the incidence of chronic rejection within this series was lower among living-related recipients versus cadaveric recipients of donor organs.     

The adverse impact of cytomegalovirus infection on clinical outcome in cyclosporine-prednisone treated renal allograft recipients

Cytomegalovirus (CMV) infection was diagnosed in 28% (n = 144) of 516 renal allograft recipients treated with cyclosporine-prednisone (CsA-Pred) immunosuppressive therapy. The majority of infections produced either asymptomatic (n = 37) or mild-to-moderate (n = 75) clinical disease, while 10% were lethal (n = 14). Transplantation from a seropositive donor to a seronegative recipient was associated with an increased incidence of (CMV) infection but did not predispose to more severe clinical disease. Similarly, donor source (cadaver [CAD] vs. living-related donor [LRD]), age greater than or equal to 45 years, and antecedent pulse steroid therapy for the treatment of acute rejection were not correlated with clinically more severe disease. An increase in serum creatinine to greater than or equal to 25% of preinfection nadir values occurred in association with CMV infection in 106 patients, returning to nadir values or below in 74.5% of these individuals. CMV infection did not impact on actual patient survival among recipients of LRD or CAD allografts or on actual 1-year HLA-haploidentical or HLA-identical LRD graft survival. In contrast, actual 1-year cadaveric graft survival was significantly lower among CMV-infected (n = 95) vs. uninfected (n = 198) patients (75.8% vs. 87.8%, P = .01). In association with the finding of reduced actual 1-year CAD graft survival, CMV-infected patients were found to be more predisposed to develop acute rejection episodes. Of the CMV-infected CAD graft recipients, 48.4% developed greater than or equal to 1 acute rejection episode during the first year following transplantation vs. 25.3% of their uninfected counterparts (P less than .001). The impact of CMV infection in CsA-Pred treated renal transplant recipients does not differ substantially from that reported historically in association with prednisone-azathioprine immunosuppressive therapy.     

Evolving concepts in the diagnosis, pathogenesis, and treatment of chronic hepatic allograft rejection.

Chronic hepatic allograft rejection is characterized by the histological findings of ductopenia and a decreased number of hepatic arteries in portal tracts in the presence of foam cell (obliterative) arteriopathy. Recent studies have extended the histological spectrum of chronic rejection to include the presence of biliary epithelial atrophy or pyknosis involving the majority of small ducts present in the liver biopsy specimen. Overall, the incidence of chronic rejection in adults appears to be decreasing and is currently approximately 4%. However, the incidence of chronic rejection in pediatric liver transplant recipients has been more stable and ranges from 8% to 12% in most studies. Clinical risk factors associated with chronic rejection include: underlying liver disease, HLA donor-recipient matching, positive lymphocytotoxic cross-match, cytomegalovirus infection, recipient age, donor-recipient ethnic origin, male donor into female recipient, number of acute rejection episodes, histological severity of acute rejection episodes, low cyclosporine trough levels, and retransplantation for chronic rejection. Chronic rejection, once diagnosed, frequently leads to graft failure; however, a number of reports indicated 20% to 30% of the patients with this diagnosis may respond to additional immunosuppressive therapy or even resolve spontaneously receiving baseline immunosuppression. Newer immunosuppressive agents, such as tacrolimus and mycophenolate, may successfully reverse chronic rejection, particularly when it is diagnosed in its early histological stages.     

Similar risk profiles for post-transplant renal dysfunction and long-term graft failure: UNOS/OPTN database analysis

BACKGROUND: Renal dysfunction measured by serum creatinine (>1.5 mg/dL) at 1 year post-transplant correlates with long-term kidney graft survival. The purpose of this study was to compare the risk factors for elevated serum creatinine (SCr) >1.5 mg/dL at 1 year post-transplantation, and for long-term graft failure. METHODS: Between 1988 and 1999, 117,501 adult kidney transplants were reported to Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS). Of these, 96,091 were functioning at 1 year and SCr was available on 85,135 transplants. Donor and recipient demographics (age, sex, and race), transplant [living vs. cadaveric, previous transplantation, panel reactive antibody (PRA), human leukoocyte antigen (HLA) mismatch, cold ischemic time (CIT) and post-transplant delayed graft function (DGF), use of azathioprone vs. mycophenolate mofetil (MMF), cyclosporine A (CsA) vs. tacrolimus (Tac)], induction antibody, acute rejection within 1 year variables were used in the logistic regression model to estimate odds ratio (OR) for elevated 1 year serum creatinine (SCr). A Cox proportional hazard model was used to estimate the relative risk (RR) for long-term kidney graft failure with and without censoring for death with a functioning graft. RESULTS: Five-year actuarial graft survival for living donor transplant with SCr >1.5 and 1.5 mg/dL) declined from 54.5% in 1988 to 42.3% in 1999. There was a strong concordance between the key variables, such as cadaveric transplant, increasing CIT, HLA mismatch, DGF, and acute rejection, recipient race (black), younger age, and nondiabetics status; and donor race (black) and older age for elevated SCr and long-term graft failure. CONCLUSION: Donor (age), race (black), recipient race (black), immunologic variables (HLA mismatch, DGF, acute rejection) were identified as important risk factors for elevated SCr at 1 year post-transplantation and long-term graft failure. Elevated SCr should be used as a short-term marker for predicting long-term transplant survival.     

Influence of HLA compatibility on success with living-related pediatric liver transplantation

It is not clear how HLA compatibility influences acute rejection and postoperative complications in cadaveric liver transplantation. Even less is known about this factor in pediatric living-related liver transplantation (LRLT). This research assessed HLA compatibility relative to rejection rates and complications in pediatric LRLT. The study retrospectively investigated data from 14 pediatric LRLTs in which the donor and recipient HLA genotypes were determined preoperatively. Three recipients (21.4%) developed biliary complications (two biliary leakage, one bile duct stenosis). Three others (21.4%) developed vascular complications (two hepatic artery thrombosis, one hepatic artery stenosis). Eight recipients (57.1%) were diagnosed with acute rejection. The incidence of acute rejection was not correlated with the number of HLA mismatches (P > .05), or with the number of HLA class I mismatches (P > .05); however, it was negatively correlated with number of HLA class II mismatches (P = .02). Arterial and biliary complications were not correlated with any of these categories of HLA compatibility. In conclusion, the data from this small group of patients provided no evidence that closeness of donor-recipient HLA matching influences outcome in pediatric LRLT.