The study reviews the incidence, timing, and outcome of infectious enteritis (IE) after intestinal transplantation (ITx).
A retrospective review of all patients who underwent ITx at a single ...institution between 1991 and 2003 was undertaken using database and medical records. Standard statistical analyses were performed.
Of 33 ITx recipients, 13 (39%) developed 20 culture- or biopsy-proven episodes of IE. Recipient demographics included the following: 10 males, median age 34 (10-585) months, 11 liver + intestine grafts, and two isolated intestine grafts. Infections were diagnosed a median of 76 days (32-1,800 days) after ITx. There were 14 viral (one cytomegalovirus, eight rotavirus, four adenovirus, one Epstein-Barr virus), three bacterial (Clostridium difficile), and three protozoal (one Giardia lamblia, two Cryptosporidium) infections. The bacterial infections tended to present earlier than the viral infections, and the most frequent presenting symptom was diarrhea. Complete resolution was achieved in 17 (94%) incidences with the appropriate antimicrobial or conservative therapy. It was interesting that there were seven rejection episodes documented by biopsy at the approximate time of diagnosis of IE. There were two graft losses: one because of adenoviral enteritis and one because of rejection after rotavirus enteritis. Three-year patient survival is 74% with no deaths directly attributable to IE.
IE can occur in 39% of recipients after ITx. Viral agents are the cause in two thirds of the cases. With supportive care and appropriate treatment, resolution is possible in the majority of cases. Differentiating rejection and infection on histopathology can be difficult and relies on cultures and immunostaining.
Death occurs in half of all children with fulminant hepatic failure (FHF). Although liver transplantation (LT) is potentially life-saving, there are only a few published series with limited ...experience. The aim was to examine predictors of survival after LT for FHF.
Between 1984 and 2008, all LT for FHF performed in recipients less than or equal to 18 years of age were analyzed from a prospectively maintained database using 35 demographic, laboratory, and operative variables. Unique calculated variables included creatinine clearance (cCrCl) and Pediatric End-Stage Liver Disease score (PELD). Study end-points were patient and death censored graft survival. Median follow-up was 98 months. Statistical analysis involved the log-rank test and Cox proportional hazards model.
A total of 122 children underwent 159 LTx. Cryptogenic was the primary etiology (70%) and the median age was 53 months. The significant (P < 0.05) univariate predictors of worse graft survival were: recipient age <24 months, cCrCl <60 mL/min/1.73m, PELD >25 points, and warm ischemia time >60 minutes. The significant (P < 0.05) univariate predictors of worse patient survival were: recipient African-American and Asian race, recipient age <24 months, cCrCl <60 mL/min/1.73m, and time from onset jaundice to encephalopathy <7 days. On multivariate analysis, survival was significantly impacted by 4 variables: cCrCl <60 mL/min/1.73m (GRAFT and PATIENT), PELD >25 points (GRAFT), recipient age <24 months (GRAFT), and time from onset jaundice to encephalopathy <7 days (PATIENT). While overall 5- and 10-year survival was 73% and 72% (GRAFT) and 77% and 73% (PATIENT), these were significantly worse when a combination of multivariate risk-factors were present.
This data from a large, single-center experience demonstrates that LT is the treatment of choice for FHF and results in durable survival. Analysis revealed 4 novel outcome predictors. Young children with rapid onset acute liver failure are a high-risk subpopulation. Unique to this study, cCrCl and PELD accurately predicted the end-points. This analysis identifies patient subpopulations requiring early aggressive intervention with LT.
To develop a prognostic model that determines patient survival outcomes after orthotopic liver transplantation (OLT) using readily available pretransplant variables.
The current liver organ ...allocation system strongly favors organ distribution to critically ill recipients who exhibit poor survival outcomes following OLT. A severely limited organ resource, increasing waiting list deaths, and rising numbers of critically ill recipients mandate an organ allocation system that balances disease severity with survival outcomes. Such goals can be realized only through the development of prognostic models that predict survival following OLT.
Variables that may affect patient survival following OLT were analyzed in hepatitis C (HCV) recipients at the authors' center, since HCV is the most common indication for OLT. The resulting patient survival model was examined and refined in HCV and non-HCV patients in the United Network for Organ Sharing (UNOS) database. Kaplan-Meier methods, univariate comparisons, and multivariate Cox proportional hazard regression were employed for analyses.
Variables identified by multivariate analysis as independent predictors for patient survival following primary transplantation of adult HCV recipients in the last 10 years at the authors' center were entered into a prognostic survival model to predict patient survival. Accordingly, mortality was predicted by 0.0293 (recipient age) + 1.085 (log10 recipient creatinine) + 0.289 (donor female gender) + 0.675 urgent UNOS - 1.612 (log10 recipient creatinine times urgent UNOS). The above variables, in addition to donor age, total bilirubin, prothrombin time (PT), retransplantation, and warm and cold ischemia times, were applied to the UNOS database. Of the 46,942 patients transplanted over the last 10 years, 25,772 patients had complete data sets. An eight-factor model that accurately predicted survival was derived. Accordingly, the mortality index posttransplantation = 0.0084 donor age + 0.019 recipient age + 0.816 log creatinine + 0.0044 warm ischemia (in minutes) + 0.659 (if second transplant) + 0.10 log bilirubin + 0.0087 PT + 0.01 cold ischemia (in hours). Thus, this model is applicable to first or second liver transplants. Patient survival rates based on model-predicted risk scores for death and observed posttransplant survival rates were similar. Additionally, the model accurately predicted survival outcomes for HCV and non-HCV patients.
Posttransplant patient survival can be accurately predicted based on eight straightforward factors. The balanced application of a model for liver transplant survival estimate, in addition to disease severity, as estimated by the model for end-stage liver disease, would markedly improve survival outcomes and maximize patients' benefits following OLT.
53-OR Hickey, Michelle J; Wozniak, Laura J; Smith, Tiffany ...
Human immunology,
11/2013, Letnik:
74
Journal Article
Recenzirano
Aim The role of donor-specific HLA antibodies (DSA) following liver transplantation (LTx) is not clearly established. Our aim was to assess the presence of DSA in pediatric LTx recipients. We ...hypothesized that DSA would be detected (+DSA) in patients with late allograft dysfunction due to de-novo autoimmune hepatitis (d-AIH). Methods Serum was collected at routine clinic visits from 50 pediatric LTx recipients a mean of 11.8 ± 5.3 years post LTx, and classified into four clinical phenotypes: non-tolerant with biopsy-proven late acute cellular rejection (n = 6) and/or d-AIH (n = 12); stable with normal liver function on maintenance tacrolimus (n = 25); tolerant with normal liver function off immunosuppression ⩾2 years (n = 7). Samples were blinded and antibody detection was performed using LABScreen HLA Class I and II Single Antigen beads (One Lambda) and Luminex multiplex technology. Descriptive statistics and multivariate logistic regression were performed with results reported as means and odds ratios (OR). Results HLA antibodies were detected in 28/50 (56%) of patients, with the majority of DSA directed against HLA Class II DR or DQ loci (40% and 52%, respectively). Patients with +DSA had a mean of 1.8 (range 1-4) DSA with a mean MFI of 11681 ± 8227. Patients with +DSA were younger at LTx (2.4 ± 2.9 vs 5.4 ± 5.4 years, p = 0.01). There were no differences in other clinical variables including sex, primary diagnosis, history of re-LTx, and early acute rejection. Age in years at LTx (OR 0.5, p = 0.01), history of post transplant lymphoproliferative disorder (OR 0.1, p = 0.01) and late rejection (OR 27, p = 0.02) are the strongest predictors of +DSA. Patients with d-AIH tended to be +DSA (10/12 patients, p = 0.05), a trend that was not observed in the other phenotypes. +DSA is the strongest multivariate predictor of d-AIH (OR 19, p = 0.03). Conclusions DSA are common after pediatric LTx and detected more frequently in patients with d-AIH, suggesting d-AIH may be a form of antibody-mediated rejection.
Alcohol sclerotherapy is useful for the treatment of biliary cutaneous fistulas in patients who have undergone hepatic resection. The same principle can be applied for transplant recipients with ...isolated draining biliary ducts. Percutaneous therapy of isolated draining biliary ducts with absolute alcohol (ie, 100% ethanol) was successfully performed in a 7-year-old patient who had undergone orthotopic liver transplantation. The increasing use of segmental living and split cadaveric liver grafts, with the subsequent increase risk in biliary complications, necessitates more efficient therapy for isolated draining bile ducts.
Alagille syndrome is one of the most common inherited disorders that cause chronic liver disease in children. Early reports suggested a benign course in these patients. Subsequent reports showed ...significant morbidity and mortality. This study was designed to analyze the long-term clinical course in Alagille syndrome.
The records of children with Alagille syndrome seen during a 20-year period were reviewed.
Forty-three patients were identified. Liver disease was diagnosed before 12 months of age in 95%. The frequencies of renal anomalies (50%) and intracranial hemorrhage (12%) were significant. The high incidence of chronic otitis media (35%) has not been reported previously. One patient had a renal transplant. Vascular compromise as a pathologic mechanism for some characteristics of the syndrome is also suggested by the presence of small bowel stenosis and atresia, tracheal and bronchial stenosis, renal artery stenosis, middle aortic syndrome, and avascular necrosis of the humeral and femoral heads. Twenty (47%) patients underwent liver transplantation. Five of six who underwent Kasai procedure required liver transplantation. Twelve died (28%), five after liver transplantation. One patient died of intracranial bleeding. Sixteen (37%) without liver transplantation and 15 (35%) who underwent liver transplantation are alive.
Some patients with early-onset and more severe liver disease can benefit from liver transplantation. Careful and complete assessment should be made of infants with a cholestatic syndrome, to avoid misdiagnosis and unnecessary Kasai procedures. Our observation of vascular compromise in various organ systems suggests that notch signaling pathway defects affect angiogenesis in Alagille syndrome.
This study analyzes the role of T lymphocytes and neutrophils (PMN) in intestinal ischemia and reperfusion injury (IRI) using either P-selectin blockade or elimination.
Using a model of severe mouse ...warm intestinal IRI, the following groups were performed: group 1: wild type C57BL6 no treatment; group 2: wild type treated with r-PSGL1-Ig; group 3: C57BL6 genetically deficient in P-selectin. Survival was assessed at day 7; intestine was assayed for histopathology, apoptosis, myeloperoxidase (MPO), inflammatory cytokines, hemoxygenase-1 (HO-1), and CD3 lymphocytes. Standard statistical comparison was undertaken.
The survival was significantly (P < 0.01) improved in the treatment groups: group 1, 50%; group 2, 90%; group 3, 100%. Graded histopathology and crypt apoptosis were improved in groups 2 and 3. MPO and CD3 positive cells were significantly reduced in groups 2 and 3. A significant reduction in inflammatory/Th1-type cytokines was seen in groups 2 and 3 as compared to group 1. Conversely, a significant increase in Th2-type cytokines and HO-1 production was seen selectively in groups 2 and 3.
This study demonstrates the importance of P-selectin signaling in warm, murine intestinal IRI in that either the blockade of or the genetic deficiency in P-selectin confers a survival advantage and reduction in tissue injury/inflammation. The mechanism involves a reduction of PMN and CD3 T cell infiltration and an alteration in the cytokine microenvironment in favor of a Th2 profile. These data implicate T lymphocyte as an important regulatory cell in this inflammatory process.
Intestinal transplantation (ITx) is severely limited by ischemia-reperfusion (I/R) injury. This study investigates I/R injury and ameliorates its consequences by using a recombinant protein targeted ...against selectins (recombinant P-selectin glycoprotein ligand-immunoglobulin rPSGL-Ig).
An isogeneic model of ITx was undertaken with control animals (no therapy) and treatment animals (rPSGL-Ig). Survival was assessed. Separate groups underwent an analysis examining tissue at multiple time points after I/R injury including histopathology; myeloperoxidase staining; immunostaining for CD3 and ED2; polymerase chain reaction analysis of interleukin (IL)-8/cytokine-inducible neutrophil chemoattractant, IL1beta, IL-6, interferon-gamma, IL-2, IL-4, and IL10; and western blots for hemoxygenase-1, BCL-2, and BCL-xl. Standard statistical analysis was undertaken.
Treatment with rPSGL-Ig resulted in significantly improved survival after ITx. Analysis demonstrated diminished injury on histopathology and reduced tissue infiltration of neutrophils and lymphocytes. Significant differences in the cytokine profile after ITx were seen between the two groups including the production of inflammatory cytokines at 24 hr and the Th1 and Th2 cytokines at 2 and 4 hr. Last, treatment resulted in increased production of hemoxygenase, BCL-2, and BCL-xl.
The results of this investigation of I/R injury after ITx revealed that rPSGL-Ig treatment led to marked improvement in outcome. The mechanism of action seems to involve the blockade of neutrophil and lymphocyte infiltration leading to a decreased inflammatory response possibly driven by Th2 cytokines. The results not only lend insight into the mechanisms behind I/R injury after ITx but also demonstrate a potential therapeutic modality to ameliorate its consequences.
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