Background. Hepatic artery thrombosis (HAT) after orthotopic liver transplantation (OLT) is associated with significant morbidity and mortality. Factor V Leiden (FVL) mutation is the most common genetic defect that predisposes to thrombosis. The reconstruction of hepatic artery with arterial graft is a documented risk factor for HAT. However, the relationship among FVL mutation, arterial graft, and HAT remains to be determined.Methods. We randomly genotyped 485 patients who underwent OLT from April 2002 to January 2011 and studied the incidence of Hepatic artery thrombosis in the presence of FVL mutation.Results. Of 485 patients, 21 patients (4.3%) developed HAT (13 male, 8 female); 10 patients (4 male, 6 female) were heterozygous for the FVL mutation. The incidences of HAT in patients without versus with the FVL mutation were 3.8% and 30% (P = .007). Of patients with HAT, 8 hepatic arteries were reconstructed with infrarenal aortic conduits. All 3 patients (100%) with vs 5 (28%) without FVL who received arterial grafts developed HAT (P = .042).Conclusion. Our study suggested that the FVL mutation may be a risk factor for HAT in liver transplantation; the risk is augmented in the presence of an arterial graft.

Background: We recently established a novel immunotherapy with activated donor liver NK cells for the liver transplant patients with hepatocellular carcinoma (HCC). In this procedure, we added an anti-CD3 mAb, OKT3, to the culture medium a day before the inoculation in order to inactivate CD3+ alloreactive T cells. Unexpectedly, IL-2/OKT3 treated liver NK/NKT cells could mount anti-hepatitis C virus (HCV) responses in HCV-infected liver transplant recipients (Ohira, et al. JCI 2009; 3226). Since OKT3 was recently out of market, we had been seeking alternative antibodies in this immunotherapy. In this study, we evaluated some alternative reagents to affect the NK cells and T cells in culture systems. Methods: We compared the effect of three commercially available reagents (GMP CD3 pure mAb [GMP CD3, Miltenyi Biotec], Thymoglobulin [ATG], and Alemtuzumab [AL]) in vitro culture. To determine the effect of these agents on NK cell function, freshly isolated peripheral blood mononuclear cells or donor graft liver derived mononuclear cells were cultured for 3 days in the presence of rhIL-2 (1,000 U/ml). One day before the cell analysis, these agents were added in the culture system. The effect of agents was tested on the basis of the following parameters: NK cell phenotype, remaining T cells, cytotoxicity against K562 cells, cytokine production of NK cells, and anti-HCV activity with HCV genomic replicon cells. Results: Addition of OKT3 (1mg/ml) or GMP CD3 (1mg/ml) significantly decreased T cell population. In contrast, ATG only showed a trend toward reduced T cells and AL did not affect T cell population in the culture system (Fig. 1A). IL-2 stimulated LMNCs showed a significantly increase in TRAIL and NKp44 (p< 0.05). OKT3 and GMP CD3 did not affect the NK cell phenotype, but ATG and AL significantly decreased the expression of CD16 on NK cells (p< 0.01) in the dose dependent manner. These CD16+ NK cells were lysed by the complement dependent cytotoxicity. We next analyzed the cytotoxicity and anti-HCV effect of cultured LMNCs and PBMCs. OKT3 and GMP CD3 did not affect NK cell-mediated killing against K562 targets but ATG and AL dampened their cytotoxicity. Interestingly, binding of these T cell depletion antibodies to NK cells lead to anti-HCV effect via interferon-γ production (Fig. 1B).[Figure 1]Conclusions: The effect of GMP CD3 on the ex vivo culture system is the almost same as OKT3. Therefore, a phase I trial has been under way to investigate the safety and anti-tumor effects of donor liver NK cells treated with IL-2/GMP CD3. Our studies also suggest that T cell depletion antibodies impact NK cells in unexpected ways.

Introduction: Long term survival of intestinal transplant patients is hampered by rejection episodes. Currently protocol endoscopy of the graft and biopsies are the only way to predict a rejection episode. Symptoms and clinical findings frequently appear when injury to the graft is irreversible. In this report we present our initial data of putative candidate biomarkers of graft rejection in peripheral blood of intestinal transplant patients. Materials and methods: Gene expression analysis was performed in peripheral blood of intestinal transplant patients. The results were matched with concurrent graft biopsies using bioinformatics. Peripheral blood samples of intestinal transplant patients were collected in Tempus Blood RNA tubes. Concurrent graft endoscopies were performed and graft biopsies were obtained at the time of the blood samples, to match the results of the gene expression analysis with the state of the graft. Whole genome microarray analysis using the Illumina-HT12 Expression beadchip microarray was performed. The gene expression levels in patient samples were compared to those in a pool of healthy volunteers. Bioinformatics analysis was performed using the MetaCore 6.3 software from GeneGo Inc. and the Pathway Studio 7.1 software from Ariadne Genomics. Results: Peripheral blood samples (n=11), of 3 adult patients [transplant day (n=1), no rejection (n=1), minimal rejection (n=2), mild rejection (n=5) and severe rejection (n=2)] were collected. Bioinformatics: Enrichment Analysis: The three most affected pathways differentially expressed in rejection versus a pool of healthy volunteers were related to protein translation: translation initiation, translation elongation termination, and translation in mitochondria, with p-values for all rejection stages in all patients in the 10-4 to 10-18 range. No significant enrichment was observed for these categories in the day of transplant sample. In addition to translation, significant enrichment of several immune response categories was observed in rejection samples. Subsequent gene set enrichment analysis verified these results. The level of enrichment was very high (p-values of 10-5 - 10-60) and increased with the level of rejection in all patients. Genes significantly down-regulated in translation related gene sets included ribosomal proteins RPL13A, RP L22, RPS23, RPL13 and RPL10A, that could be used as potential biomarkers for future experiments. These results were further verified with the use of additional samples of 2 more small bowel transplant patients. Conclusion: In this pilot study we found a list of genes (involved in translation) significantly down-regulated in the peripheral blood of intestinal transplant patients during rejection. Our hypothesis, derived from this project, is that down-regulation of translation in peripheral blood mononuclear cells occurs early during the course of rejection and persists and progresses with the severity of the rejection episode as determined by concurrent graft biopsies.

Introduction: The present study provides the long term follow up of our adult liver transplant recipients induced with alemtuzumab (Campath 1H, C1H). Methods: This is a retrospective analysis of patients who underwent liver transplantation using C1H induction at our Center from 2001 until 2010. C1H was not administered to patients with Hepatitis C (HCV). Maintenance immunosuppression was with half the usual dose of tacrolimus. Patients receiving steroids for their underlying (autoimmune) disease were maintained on the same dose after transplantation. No other steroids were given except for acute rejection episodes. Patients transplanted before April 2004 received four doses of C1H starting pre-operatively, whereas those transplanted afterwards received two or a single dose of C1H starting immediately after the transplant. Results: Three hundred and four patients (192 male, 112 female), received a liver allograft with C1H induction immunosuppression, Seventy three patients received 4 doses of C1H, the first one pre-operatively, 231 patients received two (n=77) or one (n=154) dose, starting immediately post-operatively. One, three, five and seven year patient survival was 91.4%, 87.35%, 84.62% and 82.83%. One, three, five and seven year graft survival was 89.47%, 84.69%, 80.84% and 78.36%. One, three, five and seven year freedom from rejection was 57.79%, 52.32%, 47.43%, 46.02%. There was no significant difference in incidence of rejection between patients that received the first dose of Campath-1H before or after the transplant. Average tacrolimus trough levels were between 5-7 ng/ml for the first 2 years post transplantation and less than 5 ng/ml thereafter. Twelve patients have required long term renal replacement therapy to date, five requiring kidney transplantation and seven additional patients dialysis. One, three, five and seven year freedom from renal replacement was 99.64%, 98.89%, 96.03%, 92.77%. Seven patients were weaned off immunosuppression 3-7 years post-transplantation. Conclusion: C1H induction with low dose tacrolimus maintenance immunosuppression leads to good outcomes in non-HCV liver transplant recipients. Postoperative administration of C1H is as effective as preoperative exposure.

Aim: Our aim was to assess the risk of potential transmission of autoimmune diseases from cadaveric donors to recipients of allogeneic solid organ transplantation. Patients and methods: Donors younger than 25 years whose organs were procured between 2001 and 2010 were included in the study. Past history of autoimmune diseases were assessed from the charts. Recipients of any solid organ from these donors were track for the potential occurrence of autoimmune diseases. Results: A total of 449 donors were included, only 5 of them suffered from some type of autoimmune disease: 2 type I diabetes, 2 past history of idiopathic thrombocytopenic purpura, and 1 hypothyroidism. In the 14 recipients beneficed from these donors, organ distribution were as follows: 4 single kidney, 3 liver, 3 heart, 2 both kidneys, 1 both lungs, and 1 multivisceral. Median follow-up time was 4.9 (0.0-9.9) years. Any patient showed any clinical manifestation of related to their respective donor autoimmune disease or any other. Two recipients (1 liver, 1 both lungs) died in the early postoperative period, two died because of rejection in the short term. Conclusions: Past history of acute autoimmune disorders or active chronic autoimmune diseases is not contraindication for solid organ donation.

Background: Children with short bowel syndrome starting in the neonatal period (NB- SBS) are exposed to many live-threatening complications that can affect their outcome before and after transplantation. Our aim was to assess the outcome of this group of children in a single transplant center. Material and methods: Retrospective review of pediatric intestinal transplants performed between 1994 and 2010 at our center. All patients with short bowel syndrome of neonatal onset were included. Those with motility disorders or intestinal epithelium disease but normal bowel length were not included in spite of the congenital character of these diseases. Pre-transplant status, weight, time on the waiting list, type of graft, patient survival, graft survival and immunological complications were compared between patients with NB-SBS and the rest of the children included. T-Student test, Chi-square tests and log-rank were used to compare quantitative, qualitative and survival data respectively. Results: A total of 180 pediatric intestinal transplants were performed in children between 1994 and 2010. Of them, 104 (57%) suffered from short bowel syndrome of neonatal onset, 96 (53%) were male and 85 (46%) females. Patient survival at 1, 5 and 10y were similar between patients with NB-SGS and other children (61, 42, 32% vs 62, 42, 34%; respectively). Graft survival was also similar in the three periods for the two groups (61, 39, 33% vs 51, 35, 32%, respectively). Waiting time was lower but not significantly in the NB-SBS group (77.3 vs 98.8 days) Type of graft distribution was similar in both groups except for the absence of MMV in the group of NB-SBS that contrast to 11% of these grafts in other children. Weight at transplantation was significantly lower in the NB-SGS group (10.2±16.8 vs 17.5±6.8 Kg). Regarding pre-transplant status patients in the NB-SGS were more likely to be in the ICU (24. 2 vs 10.9%) and less at home (44.4 vs 62.2%) compared to patients in the other group. Pre transplant creatinin level was similar the two groups but pre transplant albumin, bilirubin, INR and PT were more seriously impaired in patients in the NB-SGS group compared to other children. Recipient/donor weight rate was similar in both groups (1.2 vs 1.1) in NB-SGS vs others. PTLD was most frequent in children with NB-SBS compared to others (18.1 vs 8.5%). Rejection, GVHD and infectious complications were similar in the two groups. Conclusions: Patients suffering from NB-SGS had similar patient and graft survival compared to the rest of children that received an intestinal transplant. Liver function tests were more impaired in the NB-SGS group, and they were more prone to be in the ICU at the moment of transplant than the rest of children. The rest of pre and post-transplant variables examined did not show any difference.

Introduction: Liver transplantation (LT) is closely associated with blood transfusion practices since the first transplants. Requirement of blood has been reduced by advance and refinements in patient selection, transfusion methods, and surgical technique. LT without any blood product became real clinical practice in patient with stable preoperative condition. The aim of this study was to analyze the pre-operative, intra-operative, post-operative factors associated with LT without intraoperative red blood cell (RBC) transfusion. Methods: Four hundreds forty four adult patients were selected from our database due to the less than 5 units of RBC transfusion. Out of 444, 51 patients were selected as study group due to no RBC transfusion and 389 patients were selected as control group due to the 1-5 units of RBC transfusion during LT surgery. Coagulations were monitored intraoperatively and corrected if clinically indicated. Aprotinin was not used. Auto transfusion of blood salvaged was used routinely following our protocol. Independent factors were analyzed to find a link with no RBC transfusion. Survival curve was generated by Kaplan Meier methods and compared with log rank test. Results: Factors of study group vs. control group were as follows: MELD score was 20 vs. 20. Calculated MELD score was 12 vs. 12. Cold ischemic time was 429 vs. 425 min. Warm ischemic time was 37.0 vs. 37.1 min. Donor age was 41 vs. 39 yrs. Use of piggyback technique (PB) was 94% (n=48) vs. 92% (n=363). Use of Conventional cava reconstruction was 6% (n=3) vs. 8% (n=30). There were no statistically significant differences in demographic factors including donor age, recipient age, primary liver diagnosis, MELD score, CIT, WIT, INR, Cr, bilirubin, and amounts of auto-transfusion, cava reconstruction methods between the groups. Amount of fresh frozen plasma is significantly less in study group (P< 0.05). One, 3, 5 years' patient and graft survival were 92%, 88% 79% and 92%, 88%, 79% in study group and 89%, 82%, 76% and 84%, 78%, 71% in control group respectively. There was no statistical difference in patient and graft survival between the groups. Conclusion: Preoperative factor have limited predictive power for no intra-operative RBC transfusion in patient with stable condition. No transfusion could be achieved by LT. LT without transfusion did not show survival benefit. Surgical technique and auto transfusion of blood salvaged may play roles to decrease the intra-operative RBC requirements.[Figure 1]

Introduction: The advances of immunosuppression and post-operative follow up have contributed to an improvement of the long term survival of liver transplant recipients. However, complications related to long term immunosuppression affect both long term survival and quality of life of these patients. Successful withdrawal of immunosuppression has been achieved in many liver transplant recipients. In this study we present a long term follow up of a cohort of patients that had their immunosuppression successfully withdrawn. Methods: We studied the outcome of liver transplant patients who had their immunosuppression successfully withdrawn. A total of thirty operationally tolerant patients were studied (27 men and 3 women). Twenty three of them were weaned off immunosuppression during a withdrawal study that took place about 10 years ago. The remaining seven patients were part of a cohort of patients that were transplanted more recently under Campath-1H induction immunosuppression and were weaned during the last 5 years. Results:Patient Survival:Patient, graft survival: With a follow up until end of January 2012, the post-transplant follow up of the patients was from 7-20 years (average:14.15) and the off immunosuppression follow up was from 1.4-11 years, (average:7.25). There were seven mortalities. Deaths were due to cardiovascular causes (n=5): [myocardial infarct (n=3), cerebrovascular accident (n=1), pulmonary embolism (n=1)]. Other mortalities included biliary obstruction-sepsis (n=1), chronic rejection-sepsis (n=1). Average age of these patients at the time of death was 69.01 years. There were no re-transplants during this period of time. Rejection episodes: A patient presented a moderate rejection 5.3 years after immunosuppression withdrawal and was put back on maintenance immunosuppression. Renal function: Until the end of the follow up period, a patient was on dialysis and another received a kidney transplant 13.9 and 19.26 years post-transplantation respectively. Neoplasms: Six patients presented with squamous cell skin cancer (n=2), throat, kidney, lung cancer and melanoma (one each). Conclusions: Operational tolerance after liver transplantation can be achieved for a long period of time, however is not a permanent state and continuous vigilance and follow up is required to detect rejection episodes.

Citrulline has been advocated as a marker for acute cellular rejection (ACR) in intestinal transplantation; however, its significance as a forewarning in the long-term follow-up remains unknown. This study aimed to investigate the association between citrulline levels and the grading of ACR to establish a cutoff point that accurately predicts ACR beyond 3 months posttransplant in the pediatric patient population. During a 16-year period (1995–2011), a total of 13 499 citrulline samples were prospectively collected from 111 consecutive pediatric intestinal/multivisceral transplant recipients: 2155 were obtained concurrently with intestinal biopsies. There were 185 ACR episodes observed among 74/111 (67%) patients (median follow-up: 4.4 years). Citrulline levels were inversely proportional to the severity of ACR. Negative predictive values for any type of ACR (cutoff, 20 μmol/L) and moderate/severe ACR (cutoff, 10 μmol/L) were 95% and 99%, respectively. When patients were divided according to graft size, diagnostic accuracy using the same cutoff was identical. Similarly, subgroup analysis by the timing of citrulline measurement prior to biopsy varying from 1 to 7 days demonstrated comparable results. Citrulline is a potent indicator as a danger signal for ACR, being an exclusionary, noninvasive biomarker with excellent negative predictive values in the long term after pediatric intestinal/multivisceral transplant.

ackground: T cell depleting strategies have become an integral part of immunosuppressive regimens widely used for induction in solid organ transplantation. Alemtuzumab (AL) is a recombinant humanized monoclonal antibody against human CD52, a cell surface antigen expressed on B and T cells, monocytes, and natural killer (NK) cells. Although the depletion of lymphocytes would be expected to result in an increased risk of infections, some studies reported not to increase the incidence of infections. We observed early large granulocyte reconstitution in liver transplantation (LT) with AL. However, information is limited regarding the phenotype and function of liver NK cells in T cell depletion using AL. Methods: Absolute counts and proportion of NK and T cells were measured after LT with AL. We collected the mononuclear cells from the liver (LMC), peripheral blood (PBMC), spleen (SP), and lymph nodes (LN) from the donor in LT patients. Phenotype and functional differences were examined by flow cytometry and in vitro cytotoxicity assays. Anti- CD3, CD16, TRAIL, NKp30, NKp44, NKp46, NKG2D, CD52, CD56, CD94, CD117, and CD158b mAbs are used for phenotyping lymphocyte and NK cells. Results: Absolute counts of T cells remained low for 6 months. In contrast, those of NK cells had emerged with larger number since early days after LT (Fig 1A). LMC (n=7) contained high percentage of CD52- CD56+ NK cells (54.2±9.0 % especially CD56 bright 81.2±5.7 %, Fig 1B). It was statistically significant higher percentage than that of PBMC, SP, and LN (25.1%, 28.4%, and 9.3 % respectively, P< 0.05). The phenotype of almost liver NK cells showed mature type (stage5; CD94+CD117-: 99.1%). The expressions of other markers had not any differences between CD52-CD56+ and CD52+CD56+ NK cells. On the other hand, PBMC contained high percentage of CD52+CD56+ NK cells (99.3%). Donor liver NK cells had stronger cytotoxicity after IL-2 stimulation in the presence of AL. These data indicated that NK cells in PBMC were depleted but NK cells in LMC remained alive and active in LT patient with AL induction.[Figure 1]Conclusions: The liver contains high percentage of CD52-CD56+ NK cells which are mature type. The function of CD52-CD56+ NK cells had stronger cytotoxicity even in the presence of AL. These results suggest that the functionally maintained CD52-CD56+ NK cells contribute to protect the recipients from severe infections even after T cell depletion therapy such as AL induction.

BACKGROUND:Hepatopulmomary syndrome is defined by the triad of chronic liver disease, increased alveolar-arterial gradient, and evidence of intrapulmonary vasodilation. It is commonly seen in association with cirrhosis (90%). Four percent to 8% of the hepatopulmomary syndrome cases are reported in noncirrhotic portal hypertension. The management of patients with hepatopulmomary syndrome due to noncirrhotic portal hypertension is not well described.METHODS:We report a case of a 26-year-old woman who underwent liver transplantation for hepatopulmomary syndrome due to noncirrhotic portal hypertension. The patient presented with dyspnea and platypnea, requiring home oxygen therapy. She had orthodexia, severe hypoxemia, and positive bubble echocardiography consistent with hepatopulmomary syndrome. Her Model for End-stage Liver Disease score was 10. Liver biopsy revealed diffuse nodular regenerative hyperplasia.RESULTS:The patient underwent liver transplantation with Model for End-stage Liver Disease exception points. Her oxygen requirements gradually improved during the postoperative period. The patient's symptoms and hypoxemia resolved at 15-month follow-up posttransplantation.CONCLUSION:We suggest hepatopulmonary syndrome in this setting is an indication for liver transplantation despite the absence of cirrhosis.

tryphonopoulos, P.1; Ruiz, P.2; Nishida, S.3; Weppler, D.4; Levi, D.3; Moon, J.3; Selvaggi, G.3; Island, E.3; Tekin, A.3; Torres, M.5; Defranc, T.6; de Bonnefon, A.5; Arosemena, L.5; Tzakis, A.3 Author Information

Mycophenolate mofetil (MMF) has become an important and commonly used drug for maintenance immunosuppression therapy in recipients of all types of organ transplants. The drug is an antimetabolite that blocks the de novo pathway of purine synthesis. Although it selectively inhibits B- and T-lymphocyte proliferation, enterocytes are partially susceptible to MMF. One of the main limitations of this drug is gastrointestinal toxicity, with diarrhea the most frequently reported adverse effect. Most studies of MMF-associated gastrointestinal toxicity have been performed in patients with solid-organ transplants, although no data on changes related to MMF toxicity in bowel allografts have been published in the English literature. We evaluated mucosal intestinal biopsy tissue from patients with multivisceral transplants receiving MMF therapy. Our objective was to find morphologic changes that might be attributed to MMF toxicity, as well as changes that could differentiate MMF toxicity from acute rejection. Examination of the surface epithelium, lamina propria, and crypts in this small group of patients showed no specific changes that could be associated with MMF toxicity. Changes such as graft-vs-host disease or inflammatory bowel disease described in previous studies of solid-organ transplantation were not observed. Larger studies and the use of special stains and new markers might be necessary to characterize possible patterns of MMF toxicity and their differences from acute rejection.

BACKGROUND:The molecular mechanisms and regulation of immune-mediated rejection of organ allografts remains unclear. Recent studies have reported that small non-coding RNAs, microRNAs (miRNAs) play a critical role in the immune system via modulation of transcription and translation.PURPOSE:We hypothesized that particular miRNAs provide regulation of an ensuing intragraft immune effector response. The aim of our study was to detect miRNAs involved in acute cellular rejection (AR) in human small intestinal allografts.MATERIALS:We examined 12 small intestinal mucosal biopsies (AR, 7 cases, all grade 2 or 3) and non-rejecting (NR) allografts (5 cases, all grade 0) obtained from recipients after small bowel or multivisceral transplantation. RNA was isolated from the formalin-fixed paraffin-embedded (FFPE) biopsy samples and transcribed to cDNA. After preamplification we utilized a PCR based TaqMan Low Density Array (TLDA) containing 365 mature human miRNAs. Relative quantification was done based on pooled normal intestine using a comparative Ct method.RESULTS:We identified 62 miRNA upregulated genes in small bowels with ACR, and 35 were downregulated. Forty-two miRNA genes were upregulated in non-ACR small bowel biopsy samples (grade IND), and 45 were downregulated. The relative fold change ratio of ACR to non-ACR was calculated, and 50 upregulated and 8 downregulated miRNAs were detected as significant. Several interesting miRNAs will be evaluated further from this preliminary study. Our data suggests that intragraft miRNAs are potentially involved in the activation of a host alloimmune response to donor. These miRNAs may serve as targets for appropriate intervention and may be useful to monitor the allograft status.

tryphonopoulos, P.; Andreev, V.; Ruiz, P.; Volsky, A.; Island, E.; Selvaggi, G.; Tekin, A.; Nishida, S.; Levi, D.; Moon, J.; Weppler, D.; Defranc, T.; Torres, M.; Shin, S.; Tzakis, A. Author Information

BACKGROUND:The role of preformed donor-specific antibodies (DSAs) as a barrier to isolated intestinal transplantation (ITx) remains ambiguous; thus, a positive cross-match has not been a contraindication to ITx.OBJECTIVE:To report the case of a patient with Crohn's disease who underwent ITx and developed immediate antibody-mediated rejection on reperfusion of the allograft.METHODS:Percent reactive antibody testing was performed using pretransplantation serum samples and at transplantation using bead-based assays (Luminex, Luminex Corp, Austin, Tex) and flow cytometry solid-phase assays (FlowPRA single-antigen beads (One Lambda, Inc, Canoga Park, Calif). Serologic tests, flow cytometry cross-matching, and flow cytometry assays of C4d-binding serum antibodies were also performed. Histologic and immunofluorescent analysis of biopsy specimens was performed.RESULTS:HLA typing revealed no sharing of class I or II antigens between donor and recipient. Pretransplantation donor-specific antibodies (DSA) were present at transplantation. Cross-matching (performed during surgery) was positive for class I and II by serologic testing and flow cytometry. After reperfusion, the graft immediately developed severe ischemic injury and arteritis on mucosal biopsy specimens, with immunoglobulin deposition. The DSA C4d binding antibodies were also present. After intense immunosuppression and plasmapheresis, the graft and the biopsy histologic findings showed marked improvement (day 2). By day 7 posttransplantation, patient and graft status were stable. The patient has remained clinically stable for more than a year after transplantation.CONCLUSIONS:Pretransplant DSA in ITx can be a risk factor for immediate (hyperacute) but potentially reversible antibody-mediated rejection. Thus, pretransplantation DSA and cross-match results are critical components to be considered in patients awaiting or undergoing ITx.

tryphonopoulos, P.1; Ruiz, P.2; Weppler, D.3; Levi, D.4; Nishida, S.4; Moon, J.4; Selvaggi, G.4; Tekin, A.4; Island, E.4; Torres, M.5; Tzakis, A.4 Author Information

Undetectable hepatitis C virus (HCV) RNA [RNA(-)] before liver transplantation (OLT) has been shown to decrease the rates of disease recurrence. We sought to determine whether RNA(-) subjects differ in post-OLT recurrence (virological/VR, histological/ HR), graft failure (GF), or patient survival from RNA(+) patients using a retrospective review. From 1995 to 2004, a total of 49 patients were RNA(-) at OLT as a result of interferon-based therapy: 22 SVR and 27 with end-of-treatment response (ETR) transplanted when RNA(-) within 6 months of ET. Forty-eight RNA(+) patients were analyzed as controls. Virological recurrence (VR) was seen in 55% of RNA(-) subjects with no difference in HR between RNA(-) vs (+) groups, namely 36.7% versus 56.3% (P =.068), respectively. The RNA(+) subjects showed a lower time to HR (5.6 vs 11 months; P =.027). The SVR subjects displayed lower VR (36.4%) and histological recurrence (HR) (13.6%) compared to ETR (VR 70.4%, P =.023; HR 55.6%, P =.003) or RNA(+) (HR 56%, P =.0008). The SVR subjects, who were identified with a sensitive assay (SVR(S), lower limit < 600 IU/mL) showed no VR, HR, or GF. The 1- and 5-year survivals were 87.8%/75.6% and 89.6%/77.8% for RNA(-) and (+) groups, respectively (P =.77). In conclusion, RNA(-)-transplanted patients displayed lower VR and longer time to HR. The SVR patients showed lower VR and HR compared to ETR and RNA(+) patients.