BACKGROUND Gastroesophageal reflux is associated with poorer outcomes after lung transplant,likely through recurrent aspiration and allograft injury.Although prior studies have demonstrated a relationship between impe...BACKGROUND Gastroesophageal reflux is associated with poorer outcomes after lung transplant,likely through recurrent aspiration and allograft injury.Although prior studies have demonstrated a relationship between impedance-pH results and transplant outcomes,the role of esophageal manometry in the assessment of lung transplant patients remains debated,and the impact of esophageal dysmotility on transplant outcomes is unclear.Of particular interest is ineffective esophageal motility(IEM)and its associated impact on esophageal clearance.AIM To assess the relationship between pre-transplant IEM diagnosis and acute rejection after lung transplantation.METHODS This was a retrospective cohort study of lung transplant recipients at a tertiary care center between 2007 and 2018.Patients with pre-transplant anti-reflux surgery were excluded.Manometric and reflux diagnoses were recorded from pre-transplant esophageal function testing.Time-to-event analysis using Cox proportional hazards model was applied to evaluate outcome of first episode of acute cellular rejection,defined histologically per International Society of Heart and Lung Transplantation guidelines.Subjects not meeting this endpoint were censored at time of post-transplant anti-reflux surgery,last clinic visit,or death.Fisher’s exact test for binary variables and student’s t-test for continuous variables were performed to assess for differences between groups.RESULTS Of 184 subjects(54%men,mean age:58,follow-up:443 person-years)met criteria for inclusion.Interstitial pulmonary fibrosis represented the predominant pulmonary diagnosis(41%).During the follow-up period,60 subjects(33.5%)developed acute rejection.The all-cause mortality was 16.3%.Time-to-event univariate analyses demonstrated significant association between IEM and acute rejection[hazard ratio(HR):1.984,95%CI:1.03-3.30,P=0.04],confirmed on Kaplan-Meier curve.On multivariable analysis,IEM remained independently associated with acute rejection,even after controlling for potential confounders such as the presence of acid and nonacid reflux(HR:2.20,95%CI:1.18-4.11,P=0.01).Nonacid reflux was also independently associated with acute rejection on both univariate(HR:2.16,95%CI:1.26-3.72,P=0.005)and multivariable analyses(HR:2.10,95%CI:1.21-3.64,P=0.009),adjusting for the presence of IEM.CONCLUSION Pre-transplant IEM was associated with acute rejection after transplantation,even after controlling for acid and nonacid reflux.Esophageal motility testing may be considered in lung transplant to predict outcomes.展开更多
Background: The allo-immune response following organ transplantation constitutes one of the main determinants concerning both short- and long- term outcomes in renal graft recipients. Chemokines and their receptors pl...Background: The allo-immune response following organ transplantation constitutes one of the main determinants concerning both short- and long- term outcomes in renal graft recipients. Chemokines and their receptors play a diversified and important role, either homeostatic or inflammatory and direct different immune-competent cell types to the allograft. While deeply studied in the last two decades, controversy persists as a result of chemokines’ pleiotropic actions. We report our analysis of CCR1, CCR3, CCR7, CCL5 and CX3CL1 expression or synthesis by graft-infiltrating cells in human kidney transplants (KTx). At the same time, we tested their robustness in diagnosing acute rejection. Methods: Fine-needle aspiration biopsies (Fnab) were performed either on days 7 or 14 post-transplantation among stable KTx and on the day of acute rejection (AR) diagnosis. Fnab cytopreparations were studied by the enzymatic avidin-biotin complex staining for CCR1, CCR3, CCR7 and CX3CL1. From another subgroup of cases, Fnab samples were cultured for 48 hours and the supernatants were analysed for CCL5 by ELISA. Results: The group of AR cases showed a significantly up-regulated expression of CCR1, CCR3, CCR7 and CX3CL1 and a significantly higher synthesis of CCL5. The positive predictive values were respectively 92%, 97%, 85%, 76% and 78% and negative predictive values were by the same order, 100%, 73%, 100%, 98% and 83%. Conclusions: Our study permits us to advance that CCR1 and CCR3 play a significant and non-redundant role in acute rejection, and it is the first report of CCR3 association with rejection, probably related to CCL5. The presence inside the graft of significant up-regulation for CCR7 surmises that part of antigen presentation may be performed there without being restricted to secondary lymphoid sites. Our results with CX3CL1 confirm other reports.展开更多
Acute humoral rejection （AHR） is uncommon after ABO- compatible liver transplantation. Herein, we report two cases of AHR treated with plasmapheresis and rituximab in two ABO-compatible liver-transplant patients wit...Acute humoral rejection （AHR） is uncommon after ABO- compatible liver transplantation. Herein, we report two cases of AHR treated with plasmapheresis and rituximab in two ABO-compatible liver-transplant patients with preformed anti-human leukocyte antigen donor-specific antibodies. Patient 1 experienced a biopsy-proven AHR at day 10 post-transplant. She was treated by steroid pulses, and OKT3. Because of persisting signs of biopsy-proven AHR at day 26, she was treated by plasmapheresis and rituximab. Uver enzyme levels did not improve, and she died on day 41. Patient 2 experienced a biopsy-proven AHR on day 10 post-transplant. She was treated by steroid pulses, plasmapheresis, and rituximab. Liver enzymes returned to within normal range 18 d after diagnosis. Uver biopsies, at 3 and 9 mo post-transplant, showed complete resolution of AHR. We conclude that plasmapheresis should be started as soon as AHR is diagnosed, and be associated with a B-cell depleting agent. Rituximab may be considered as a first-line therapy.展开更多
AIM: To study effect of operation-synchronizing transfusion of apoptotic spleen cells from donor rats on acute rejection of recipient rats after liver transplantation. METHODS: Two of Wistar rats were chosen randomly ...AIM: To study effect of operation-synchronizing transfusion of apoptotic spleen cells from donor rats on acute rejection of recipient rats after liver transplantation. METHODS: Two of Wistar rats were chosen randomly for normal liver pathology control and ten of SD rats chosen randomly for liver function control as blank group (no operation). The rest of Wistar and SD rats were divided into four groups: control group (only liver transplantation), Dex group (donors receiving intraperitoneal injection of dexamethasone), SpC group (recipients receiving infusion of spleen cells of donors), Dex-SpC group (recipients receiving infusion of apoptotic spleen cells of donors), with each group except blank group, containing 10 SD rats and 10 Wistar rats, respectively. Wistar rats received liver transplantation from SD rats, in the meantime they received infusion of spleen cells of donors, which were induced by an intraperitoneal injection of dexamethasone (3 mg/(d.kg)·b.w) for three days before liver transplantation. The serum alanine transaminase (ALT), total bilirubin (T bili), liver pathological changes and survival time were analysed. Statistical analysis was carried out using SPSS 10.0 for Windows. Differences of the parametric data of ALT in means were examined by one-way ANOVA. Differences of ALT between two groups were examined by LSD. Differences of the nonparametric data of T bili in means and scores of pathology classification for acute rejection were examined by Kruskal-Willis H test. The correlations between ALT and T bili were analysed by Bivariate. Kaplan-Meier curves were used to demonstrate survival distribution. The log-rank test was used to compare the survival data. RESULTS: There were significant differences in ALT of the five groups (F= 23.164 P= 0.000), and ALT in Dex-SpC group was significantly higher than that in blank control, control, Dex, and SpC groups (P = 0.000), and ALT in SpC group was significantly higher than that in blank control (P= 0.000), control (P= 0.004), and Dex groups (P= 0.02). Results of nonparametric analysis of T bill showed that there were differences in T bill of the five groups (X2= 33.265 P= 0.000). T bili in Dex-SpC group was significantly higher than that in blank control, control, Dex, and SpC groups. T bili in SpC group was higher than that in blank control, control, and Dex groups. There were significant differences in scores of pathology classification for acute rejection in each of the groups (X2= 25.933, P= 0.000). The pathologically more serious acute rejection was found in Dex-SPC group than in other groups. No sign of acute rejection was observed in the blank control group. Slight acute rejection was observed in the control group. Slight-moderate acute rejection was observed in the Dex group. Moderate-acute rejection was observed in the SpC group. Severe-acute rejection was observed in the Dex-SpC group. The survival time in Dex-SpC group was shorter than in other groups (statistic = 11.13, P= 0.011). ALT and T bili were positively correlated (r= 0.747, P= 0.000, two-tailed). CONCLUSION: In order to reduce quantity of blood loss from rats after liver transplantation, only one of ALT or T bili is needed for liver function measurement of rats. Simultaneous injection of apoptotic spleen cells from donors induced by dexamethasone to liver transplantation rats aggravates acute rejection. One important mechanism of aggravation of acute rejection may be that apoptotic cells are not removed in time and that dead cells including apoptotic cells release inflammatory factors.展开更多
AIM: To analyze the expression levels of soluble form of CD95, CD95 ligand (sCD95 and SCD95L, respectively) in plasma and CD95 expression on CD3+cells in liver-transplanted recipients with acute rejection (AR). METHOD...AIM: To analyze the expression levels of soluble form of CD95, CD95 ligand (sCD95 and SCD95L, respectively) in plasma and CD95 expression on CD3+cells in liver-transplanted recipients with acute rejection (AR). METHODS: Peripheral blood mohonuclear cells (PBMCs) were isolated from 30 clinically liver transplanted recipients. CD95 expression on CD3+ cells was quantitatively measured by two-color fluorescence activated cell sorter (FACS) analysis. Lymphocyte surface phenotypes of CD4, CD8, CD16 and CD56 were determined by flow cytometry. Plasma levels of sCD95 and SCD95L were detected by Enzyme Linked-Immuno-Sorbent Assay (ELISA). The results were compared with that from normal healthy volunteers (n=15 individuals). RESULTS: FACS analysis showed that CD95 expression on CD3+ T cells was significantly increased in liver transplanted recipients with AR compared to that in stable recipients without rejection and infection or healthy individuals who did not undergo transplantation (18 676.93±11 588.34/molecule, 6 848.20±1 712.96/molecule, 6 418.01±2 001.95/molecule, respectively, P<0.01). Whereas no significant difference was seen between liver-transplanted stable recipients and healthy individuals. Furthermore, no significant differences were detected between each group with CD4/CD8 ratio or the percentage of CD16+56+cells. Plasma levels of sCD95 were significantly higher in transplanted recipients with AR compared to that in stable recipients or healthy individuals (391.88±196.00, 201.37±30.30, 148.83±58.25 pg/mL, respectively, P<0.01). In contrast, the plasma levels of sCD95L in liver-transplanted recipients were not significantly different from that in healthy individuals. CONCLUSION: The present results indicate that the increased CD95 expression on CD3+cells and the increased levels of sCD95 in plasma may modify the immunological situation of the recipients after transplantation or represent the ongoing graft rejection.展开更多
AIM： TO investigate the incidence and risk factors of late-onset acute rejection （LAR） and to clarify the effectiveness of our immunosuppressive regime consisting of life-long administration of tacrolimus and stero...AIM： TO investigate the incidence and risk factors of late-onset acute rejection （LAR） and to clarify the effectiveness of our immunosuppressive regime consisting of life-long administration of tacrolimus and steroids. METHODS： Adult living donor liver transplantation recipients （n = 204） who survived more than 6 mo after living donor liver transplantation were enrolled. Immunosuppression was achieved using tacrolimus and methylprednisolone. When adverse effects of tacrolimus were detected, the patient was switched to cyclosporine. Six months after transplantation, tacrolimus or cyclosporine was carefully maintained at a therapeutic level. The methylprednisolone dosage was maintained at 0.05 mg/kg per day by oral administration. Acute rejections that occurred more than 6 mo after the operation were defined as late-onset. The median follow-up period was 34 too. RESULTS： LAR was observed in 15 cases （7%） and no chronic rejection was observed. The incidence of hyperlipidemia, chronic renal failure, new-onset post-transplantation diabetes, and deep fungal infection were 13%, 2%, 24%, and 17%, respectively. Conversion from tacrolimus to cyclosporine was required in 38 patients （19%）. Multivariate analysis revealed that a cyclosporine-based regimen was significantly associated with LAR.events happen at a low incidence, supporting the safety and efficacy of the present immunosuppression regimen for living donor liver transplantation.展开更多
BACKGROUND:In liver transplantation,acute cellular rejection(ACR)is still a major complication that can lead to mortality.Bile secretion has been considered as a marker of early graft function. METHODS:The study inclu...BACKGROUND:In liver transplantation,acute cellular rejection(ACR)is still a major complication that can lead to mortality.Bile secretion has been considered as a marker of early graft function. METHODS:The study included 41 adults who received living donor liver transplantation(LDLT)at Kyoto University Hospital between April 2007 and February 2008. The patients were stratified according to the presence or absence of ACR.Bile samples were collected from donors once and from recipients every other day for the first 2 weeks after transplantation.Total bile acid(BA)and taurine-conjugated bile acid(TCBA)in bile were measured by magnetic resonance spectroscopy.The recipient/donor (R/D)BA ratio and R/D TCBA ratio were calculated. RESULTS:The ACR group(n=12)showed a greater decrease in BA post-transplantation than the non-ACR group,but this difference was not statistically significant. On both day 7 and day 9 post-transplantation the R/D TCBA was significantly different between the two groups (P=0.038 on day 7 and P=0.036 on day 9).The R/D TCBA ratio≥0.5 on days 7 and 9,and≥0.38 on day 11 post- transplantation were associated with better ACR-free survival. CONCLUSION:The recipient/donor TCBA ratio can be a predictor for ACR after LDLT as early as post- transplantation day 7.展开更多
BACKGROUND: Although many human inflammatory and autoimmune diseases were previously considered to be mediated by T helper type 1 (Th1) cells, the recently described Th17 cells play dominant roles in several of these ...BACKGROUND: Although many human inflammatory and autoimmune diseases were previously considered to be mediated by T helper type 1 (Th1) cells, the recently described Th17 cells play dominant roles in several of these diseases. We and others speculated that allograft rejection after organ transplantation may also involve Th17 cells. Episodes of acute rejection occur in 30% of liver transplants. This study aimed to determine the frequency of circulating Th17 cells in patients who had received liver transplants for benign end-stage liver disease and to identify any association between acute rejection episodes and levels of Th17 cells in the peripheral blood. METHODS: A prospective study compared Th17 cells from 76 consecutive benign end-stage liver disease patients who had undergone orthotopic liver transplantation from 2007 to 2011 with those from 20 age-matched healthy individuals. Peripheral blood samples were collected at different time points within one year after transplant. Blood samples and liver biopsies were also collected at the diagnosis of acute rejection. Percentages of circulating CD4+ IL-17+ cells were measured by flow cytometry The transplant patients were classified into two groups: a rejection group consisting of 17 patients who had an episode of acute rejection, and a non-rejection group comprising the remaining 59 patients with no acute rejection episodes Percentages of circulating Th17 cells were compared between the two groups and controls. RESULTS: The levels of circulating CD4+ IL-17+ T cells in the rejection group were higher during acute rejection than those in the non-rejection group (2.56±0.43% versus 1.79±0.44% P<0.001). The frequency of CD4+ IL-17+ cells in peripheral blood was positively correlated with the rejection activity index (r=0.79, P=0.0002).CONCLUSION: Circulating Th17 cells may be useful as a surrogate marker for predicting acute rejection in liver transplant recipients.展开更多
To identify acute renal allograft rejection biomarkers in human serum, two-dimensional differential in-gel electrophoresis （2-D DIGE） and reversed phase high-performance liquid chromatography （RP-HPLC） followed by...To identify acute renal allograft rejection biomarkers in human serum, two-dimensional differential in-gel electrophoresis （2-D DIGE） and reversed phase high-performance liquid chromatography （RP-HPLC） followed by electrospray ionization mass spectrometry （ESI-MS） were used. Serum samples from renal allograft patients and normal volunteers were divided into three groups： acute rejec- tion （AR）, stable renal function （SRF） and normal volunteer （N）. Serum samples were firstly processed using Multiple Affinity Removal Column to selectively remove the highest abundance proteins. Differentially expressed proteins were analyzed using 2-D DIGE. These differential protein spots were excised, digested by trypsin, and identified by RP-HPLC-ESI/MS. Twenty-two differentially expressed proteins were identified in serum from AR group. These proteins included complement C9 precursor, apolipoprotein A-IV precursor, vitamin D-binding protein precursor, beta-2-glycoprotein 1 precursor, etc. Vitamin D-binding protein, one of these proteins, was confirmed by ELISA in the independent set of serum samples. In conclusion, the differentially expressed proteins as serum biomarker candidates may provide the basis of acute rejection noninvasive diagnosis. Confirmed vitamin D-binding protein may be one of serum biomarkers of acute rejection. Furthermore, it may provide great insights into understanding the mechanisms and potential treatment strategy of acute rejection.展开更多
In order to evaluate the applied value of soluble intracellular adhesion molecule-1 （sICAM-l） in acute rejection （AR） following liver transplantation, the expression of sICAM-1 protein was sequentially detected by...In order to evaluate the applied value of soluble intracellular adhesion molecule-1 （sICAM-l） in acute rejection （AR） following liver transplantation, the expression of sICAM-1 protein was sequentially detected by using ELISA in serum and bile of 43 patients receiving liver transplantation. In AR group, the expression levels of sICAM-1 protein were increased 3 days before and immediately on the establishment of AR diagnosis, and there was significant difference in the expression of bile between AR group and control group （P〈0.01）. After reversion of AR with hormone intensive therapy, there was significant difference in the sICAM-1 protein expression of serum and bile between AR group and control group. It was concluded that the sequential detection of sICAM-1 protein level in serum and bile was a reliable and noninvasive method for the early diagnosis of AR after liver transplantation and was valuable to observe the curative effects of anti-AR therapy.展开更多
BACKGROUND:The 2009 H1N1 influenza A virus was first identified in April 2009 and rapidly evolved into a pandemic. Recipients of solid-organ transplants have a higher risk for severe infection because of immunosuppres...BACKGROUND:The 2009 H1N1 influenza A virus was first identified in April 2009 and rapidly evolved into a pandemic. Recipients of solid-organ transplants have a higher risk for severe infection because of immunosuppression.There are limited reports of 2009 H1N1 influenza in liver transplant recipients,especially in China. METHODS:We present a case of a 48-year-old male liver transplant recipient with 2009 H1N1 influenza A virus.He received therapy for acute rejection after transplantation and was confirmed with H1N1 virus infection. RESULTS:The patient was started on oseltamivir(75 mg, orally twice daily)and had a benign hospital course,with defervescence and resolution of symptoms within 72 hours. The follow-up chest radiograph after discharge was normal. CONCLUSIONS:The 2009 H1N1 influenza in this hospitalized transplant recipient was relatively mild,and prolonged viral shedding was not noted.Oseltamivir can be a valid measure in immunocompromised individuals.展开更多
AIMTo investigated the feasibility of using sinusoidal endotheliitis (SE) as a histological marker for liver allograft rejection.METHODSWe compared the histological features of 88 liver allograft biopsies with acute c...AIMTo investigated the feasibility of using sinusoidal endotheliitis (SE) as a histological marker for liver allograft rejection.METHODSWe compared the histological features of 88 liver allograft biopsies with acute cellular rejection (ACR) and 59 cases with no evidence of ACR. SE was scored as: (1) focal linear lifting up of the endothelial cells by lymphocytes with no obvious damage to adjacent hepatocytes; (2) focal disruption of the endothelial lining by a cluster of subendothelial lymphocytes (a group of > 3 lymphocytes); and (3) severe confluent endotheliitis with hemorrhage and adjacent hepatocyte loss.RESULTSThe sensitivity and specificity of SE was 81% and 85%, respectively. Using SE as the only parameter, the positive predictive value for ACR (PPV) was 0.89, whereas the negative predictive value for ACR (NPV) was 0.75. The correlation between RAI and SE was moderate (R = 0.44, P < 0.001) (Figure 3A), whereas it became strong (R = 0.65, P < 0.001) when correlating SE with the venous endotheliitis activity index only.CONCLUSIONOur data suggest that SE scoring could be a reliable and reproducible supplemental parameter to the existing Banff schema for diagnosing acute liver allograft rejection.展开更多
BACKGROUND The liver has traditionally been regarded as resistant to antibody-mediated rejection(AMR).AMR in liver transplants is a field in its infancy compared to kidney and lung transplants.In our case we present a...BACKGROUND The liver has traditionally been regarded as resistant to antibody-mediated rejection(AMR).AMR in liver transplants is a field in its infancy compared to kidney and lung transplants.In our case we present a patient with alpha-1-antitrypsin disease who underwent ABO compatible liver transplant complicated by acute liver failure(ALF)with evidence of antibody mediated rejection on allograft biopsy and elevated serum donor-specific antibodies(DSA).This case highlights the need for further investigations and heightened awareness for timely diagnosis.CASE SUMMARY A 56 year-old woman with alpha-1-antitrypsin disease underwent ABO compatible liver transplant from a deceased donor.The recipient MELD at the time of transplant was 28.The flow cytometric crossmatches were noted to be positive for T and B lymphocytes.The patient had an uneventful recovery postoperatively.Starting on postoperative day 5 the patient developed fevers,elevated liver function tests,distributive shock,renal failure,and hepatic encephalopathy.She went into ALF with evidence of antibody mediated rejection with portal inflammation,bile duct injury,endothelitis,and extensive centrizonal necrosis,and C4d staining on allograft biopsy and elevated DSA.Despite various interventions including plasmapheresis and immunomodulating therapy,she continued to deteriorate.She was relisted and successfully underwent liver retransplantation.CONCLUSION This very rare case highlights AMR as the cause of ALF following liver transplant requiring retransplantation.展开更多
AIM: To investigate the association between interleukin (IL)-10-1082 (G/A) promoter polymorphism and acute rejection (AR) in liver transplant (LT) recipients. METHODS: Two investigators independently searched the Medl...AIM: To investigate the association between interleukin (IL)-10-1082 (G/A) promoter polymorphism and acute rejection (AR) in liver transplant (LT) recipients. METHODS: Two investigators independently searched the Medline, Embase, China National Knowledge Infrastructure, and Chinese Biomedicine Databases. Summary odds ratios (ORs) and 95% CIs for IL-10-1082 G/A polymorphism and AR were calculated in a fixed and a random-effects model as appropriate. RESULTS: This meta-analysis included seven casecontrol studies, which comprised 652 cases of LT recipients in which 241 cases developed AR and 411 cases did not develop AR. Overall, the variant A allele was not associated with AR risk when compared with the wild-type G allele (OR = 0.94, 95% CI: 0.64-1.39). Moreover, similar results were observed when the AA genotype was compared with the AG/GG genotype (OR = 1.05, 95% CI: 0.55-2.02). When stratifying for eth-nicity, no significant association was observed among either Caucasians or Asians. Because only one study was performed in Asian patients, the result of subgroup analysis by ethnicity would not be reliable for Asians. Limiting the analysis to the studies with controls in the Hardy-Weinberg equilibrium, the results were persistent and robust. No publication bias was found in the present study. CONCLUSION: This meta-analysis suggests that IL-10-1082 G/A polymorphism may be not associated with AR risk in LT recipients among Caucasians.展开更多
Background:Translationally controlled tumor protein(TCTP),which has been verified to have a proinflammatory activity,plays an important role in allergy.However,it remains unclear whether TCTP has an impact on the acut...Background:Translationally controlled tumor protein(TCTP),which has been verified to have a proinflammatory activity,plays an important role in allergy.However,it remains unclear whether TCTP has an impact on the acute rejection(AR)after liver transplantation.Methods:Three protocols were used to delineate the role of TCTP in AR after liver transplantation.First,in rat orthotopic liver transplantation(OLT),the expression of TCTP was measured by enzyme-linked immunosorbent assay(ELISA),real-time PCR,Western blot and immunofluorescence assays.Second,in mixed lymphocyte reaction(MLR),the role of TCTP in lymphocyte proliferation was measured by carboxyfluorescein succinimidyl ester(CFSE)labeling and the impact of TCTP on inflammatory factor release was detected by cytokine arrays.Third,in human OLT,the level of serum TCTP was detected by ELISA,and the relationship between TCTP and model for early allograft function(MEAF)score was assessed by Spearman's correlation.Results:In rat OLT,AR resulted in great harm to allografts,manifesting as deterioration of liver function,increasing inflammatory factors and infiltrating lymphocytes.Meanwhile,TCTP was overexpressed in serum and allografts.Higher level of TCTP was associated with higher rejection activity index(RAI).In an MLR protocol,TCTP knockdown inhibited the proliferation of mixed inflammatory cells and significantly suppressed the release of 15 cytokines and chemokines.In human OLT,the serum TCTP was up-regulated within a week after operation.Additionally,the increasing speed of serum TCTP positively correlated with MEAF scores(r=0.449;P=0.0088).展开更多
We report a case of reversible hepatofugal portal flow after auxiliary partial orthotopic liver transplantation (APOLT) from a living donor in this study.On postoperative day 6,continuous hepatofugal portal flow was o...We report a case of reversible hepatofugal portal flow after auxiliary partial orthotopic liver transplantation (APOLT) from a living donor in this study.On postoperative day 6,continuous hepatofugal portal flow was observed in the grafted liver without portal thrombosis and obstruction of the hepatic vein.Based on histological findings,acute rejection was the suspected cause.The normal portal venous flow was restored after steroid pulse and antithymocyte globulin (ATG) therapies.The patient was discharged on the 30th postoperative day.It was concluded that hepatofugal flow after liver transplantation is a sign of serious acute rejection,and can be successfully treated by anti-rejection therapy.展开更多
To study the characteristics of acute rejection after limb allotransplantation, 29 male Sprague Dawley rats were randomly divided into 2 groups, with 15 rats in control group and 14 rats in experimental group. Each r...To study the characteristics of acute rejection after limb allotransplantation, 29 male Sprague Dawley rats were randomly divided into 2 groups, with 15 rats in control group and 14 rats in experimental group. Each rat in control group underwent limb replantation. Each rat in experimental group received limb transplantation from Wistar rat. No immnosuppressive drugs were used after operation. The circulation of the transplanted limb, time and signs of rejection, histopathological changes in the tissues of the limb graft when rejected and survival time of limb grafts were evaluated. In the control group, no signs of rejection were observed, the circulation of each replanted limb was normal, it could survive for a longer time. The experimental group showed clinical signs of rejection (sub dermal edema and erythema) after a mean time of 3.36±1.15 days, and the mean survival time of the allografts was only 7±0.78 days. Histopathological examination showed most violent rejection reaction in skin. It is concluded that with Wistar to SD limb transplantation without use of immunosuppression, rejection of the grafts would occur after a mean time of 3.36±1.15days; the earliest signs of rejection were edema and erythema of the skin, skin being the most representative component of limb graft rejection.展开更多
To investigate the imbalance state of helper T lymphocytes （Th） and cytotoxic T lymphocytes （Tc） and the roles of Thl/Th2/Th3 and Tcl/Tc2 cells in renal transplantation rejection, the percentages of these cells in...To investigate the imbalance state of helper T lymphocytes （Th） and cytotoxic T lymphocytes （Tc） and the roles of Thl/Th2/Th3 and Tcl/Tc2 cells in renal transplantation rejection, the percentages of these cells in peripheral blood of 24 cases of renal transplantation recipients with acute rejection and the dynamic changes of the CD4/CD8 ratio were determined by flow cytometry analysis, while 30 cases of healthy individuals were set up as controls. In these healthy controls, the percentages of the Thl, Th2 and Th3 cells were （ 10.45 ± 8.15） %, （5.05 ± 4.15） % and （3.90 ± 3.21 ） %, and those of Tcl and %2 cells were （9.83 ± 7.03） % and （4.51 ± 2.17） %, respectively. However, the percentages of Thl and Tcl cells in peripheral blood of the stable recipients after transplantation were （7.29 ± 5.62） % and （7.04 ± 5.15）%, showing definite reduction, while those of Th2, Th3 and Tc2 cells showed significant increase, （ 6.34 ± 5.67） %, （4.94 ± 4.14） % and （ 6.86 ± 4.42） %, respectively. In case of recipients with acute rejection, the percentages of Thl and Tcl cells appeared to be （ 18.55 ± 13.21 ） % and （ 15.84 ± 11.72） %, also showing significant increase, but those of Th2, Th3 and %2 cells appeared to be reduced, （4.19 ± 3.62） %, （3.02 ± 2.83 ） % and （3.88 ± 1.63） %, respectively. Significant differences could be detected among these three groups （ P 〈 0.05）. The CD4/CD8 ratio in cases with acute rejection was higher than those of stable recipients （2.24 ± 0.59 vs 1.95 ± 0.45）, but that of the stable recipients and healthy controls （ 1.98 ± 0.31 ） showed no any significant difference. From the above observation, it is evident that imbalance between Thl, Th2 and Th3 with Tcl and Tc2 cells may exist after renal transplantation and probably, the im- mune imbalance may be induced through the secretion of cytokines INF-γby Thl or Tcl cells , Ⅱ-4 by Th2 and Tc2 cells and TGF-β by Th3.展开更多
Objective:To explore the expression profile of miRNA in peripheral blood of patients with acute T cell mediated rejection after kidney transplantation.Method:4 patients with acute T cell mediated rejection(TCMR)after ...Objective:To explore the expression profile of miRNA in peripheral blood of patients with acute T cell mediated rejection after kidney transplantation.Method:4 patients with acute T cell mediated rejection(TCMR)after kidney transplantation were collected as experimental group.Meanwhile,4 patients under stable condition after kidney transplantation were collected as control group.The elbow blood was taken from two groups.The next generation sequencing was used to study miRNA libraries.Then,they were analyzed of variance by R language software.Results:14 miRNAs were differently expressed in the experimental group and control group,including 5 up-regulated miRNAs(P<0.05)and 9 down-regulated miRNAs(P<0.05).Conclusions:Peripheral blood miRNAs expression variations might be ideal biomarkers and reveal mechanisms for acute TCMR.展开更多
BACKGROUND： Acute cellular rejection（ACR） after liver transplantation（LT） is one of the most common problems faced by transplant recipients in spite of advances in immunosuppressive therapy. Recently, clinical tr...BACKGROUND： Acute cellular rejection（ACR） after liver transplantation（LT） is one of the most common problems faced by transplant recipients in spite of advances in immunosuppressive therapy. Recently, clinical trials reported that ursodeoxycholic acid（UDCA） reduced the incidence of ACR significantly.However, others have shown contradictory conclusion. Therefore,we performed a meta-analysis of rigorous randomized controlled trials（RCTs） to determine the efficacy of UDCA in reducing ACR after LT.DATA SOURCES： All RCTs that evaluated efficacy of UDCA as an adjuvant treatment to prevent ACR after LT were searched from PubMed/MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ScienceDirect databases and Web of Science（from January 1981 to March 2012）. There was no language limitation in these searches. Relevant abstracts of international meetings were also searched. References of each included study were searched manually.RESULTS： A total of 234 patients from four high-quality RCTs（Jadad score 4 to 5） were included in this meta-analysis.Prophylactic use of UDCA did not decrease the incidence of ACR（RR： 0.94, 95% CI： 0.77-1.16, P0.05）, steroid-resistant rejection（RR： 0.77, 95% CI： 0.47-1.27, P0.05） and the number of patients with the multiple episodes of ACR（RR： 0.60, 95% CI：0.28-1.30, P0.05）. Different intervention programs（high-dose vs low-dose UDCA; early vs delayed UDCA treatment） also did not alter the outcomes.CONCLUSIONS： UDCA, as an adjuvant treatment, was not ableto prevent ACR and steroid-resistant rejection after LT. Further trials should be done to determine whether higher dose of UDCA will be beneficial.展开更多
文摘BACKGROUND Gastroesophageal reflux is associated with poorer outcomes after lung transplant,likely through recurrent aspiration and allograft injury.Although prior studies have demonstrated a relationship between impedance-pH results and transplant outcomes,the role of esophageal manometry in the assessment of lung transplant patients remains debated,and the impact of esophageal dysmotility on transplant outcomes is unclear.Of particular interest is ineffective esophageal motility(IEM)and its associated impact on esophageal clearance.AIM To assess the relationship between pre-transplant IEM diagnosis and acute rejection after lung transplantation.METHODS This was a retrospective cohort study of lung transplant recipients at a tertiary care center between 2007 and 2018.Patients with pre-transplant anti-reflux surgery were excluded.Manometric and reflux diagnoses were recorded from pre-transplant esophageal function testing.Time-to-event analysis using Cox proportional hazards model was applied to evaluate outcome of first episode of acute cellular rejection,defined histologically per International Society of Heart and Lung Transplantation guidelines.Subjects not meeting this endpoint were censored at time of post-transplant anti-reflux surgery,last clinic visit,or death.Fisher’s exact test for binary variables and student’s t-test for continuous variables were performed to assess for differences between groups.RESULTS Of 184 subjects(54%men,mean age:58,follow-up:443 person-years)met criteria for inclusion.Interstitial pulmonary fibrosis represented the predominant pulmonary diagnosis(41%).During the follow-up period,60 subjects(33.5%)developed acute rejection.The all-cause mortality was 16.3%.Time-to-event univariate analyses demonstrated significant association between IEM and acute rejection[hazard ratio(HR):1.984,95%CI:1.03-3.30,P=0.04],confirmed on Kaplan-Meier curve.On multivariable analysis,IEM remained independently associated with acute rejection,even after controlling for potential confounders such as the presence of acid and nonacid reflux(HR:2.20,95%CI:1.18-4.11,P=0.01).Nonacid reflux was also independently associated with acute rejection on both univariate(HR:2.16,95%CI:1.26-3.72,P=0.005)and multivariable analyses(HR:2.10,95%CI:1.21-3.64,P=0.009),adjusting for the presence of IEM.CONCLUSION Pre-transplant IEM was associated with acute rejection after transplantation,even after controlling for acid and nonacid reflux.Esophageal motility testing may be considered in lung transplant to predict outcomes.
文摘Background: The allo-immune response following organ transplantation constitutes one of the main determinants concerning both short- and long- term outcomes in renal graft recipients. Chemokines and their receptors play a diversified and important role, either homeostatic or inflammatory and direct different immune-competent cell types to the allograft. While deeply studied in the last two decades, controversy persists as a result of chemokines’ pleiotropic actions. We report our analysis of CCR1, CCR3, CCR7, CCL5 and CX3CL1 expression or synthesis by graft-infiltrating cells in human kidney transplants (KTx). At the same time, we tested their robustness in diagnosing acute rejection. Methods: Fine-needle aspiration biopsies (Fnab) were performed either on days 7 or 14 post-transplantation among stable KTx and on the day of acute rejection (AR) diagnosis. Fnab cytopreparations were studied by the enzymatic avidin-biotin complex staining for CCR1, CCR3, CCR7 and CX3CL1. From another subgroup of cases, Fnab samples were cultured for 48 hours and the supernatants were analysed for CCL5 by ELISA. Results: The group of AR cases showed a significantly up-regulated expression of CCR1, CCR3, CCR7 and CX3CL1 and a significantly higher synthesis of CCL5. The positive predictive values were respectively 92%, 97%, 85%, 76% and 78% and negative predictive values were by the same order, 100%, 73%, 100%, 98% and 83%. Conclusions: Our study permits us to advance that CCR1 and CCR3 play a significant and non-redundant role in acute rejection, and it is the first report of CCR3 association with rejection, probably related to CCL5. The presence inside the graft of significant up-regulation for CCR7 surmises that part of antigen presentation may be performed there without being restricted to secondary lymphoid sites. Our results with CX3CL1 confirm other reports.
文摘Acute humoral rejection （AHR） is uncommon after ABO- compatible liver transplantation. Herein, we report two cases of AHR treated with plasmapheresis and rituximab in two ABO-compatible liver-transplant patients with preformed anti-human leukocyte antigen donor-specific antibodies. Patient 1 experienced a biopsy-proven AHR at day 10 post-transplant. She was treated by steroid pulses, and OKT3. Because of persisting signs of biopsy-proven AHR at day 26, she was treated by plasmapheresis and rituximab. Uver enzyme levels did not improve, and she died on day 41. Patient 2 experienced a biopsy-proven AHR on day 10 post-transplant. She was treated by steroid pulses, plasmapheresis, and rituximab. Liver enzymes returned to within normal range 18 d after diagnosis. Uver biopsies, at 3 and 9 mo post-transplant, showed complete resolution of AHR. We conclude that plasmapheresis should be started as soon as AHR is diagnosed, and be associated with a B-cell depleting agent. Rituximab may be considered as a first-line therapy.
基金Supported by the National Natural Science Foundation of China, No. 39970705
文摘AIM: To study effect of operation-synchronizing transfusion of apoptotic spleen cells from donor rats on acute rejection of recipient rats after liver transplantation. METHODS: Two of Wistar rats were chosen randomly for normal liver pathology control and ten of SD rats chosen randomly for liver function control as blank group (no operation). The rest of Wistar and SD rats were divided into four groups: control group (only liver transplantation), Dex group (donors receiving intraperitoneal injection of dexamethasone), SpC group (recipients receiving infusion of spleen cells of donors), Dex-SpC group (recipients receiving infusion of apoptotic spleen cells of donors), with each group except blank group, containing 10 SD rats and 10 Wistar rats, respectively. Wistar rats received liver transplantation from SD rats, in the meantime they received infusion of spleen cells of donors, which were induced by an intraperitoneal injection of dexamethasone (3 mg/(d.kg)·b.w) for three days before liver transplantation. The serum alanine transaminase (ALT), total bilirubin (T bili), liver pathological changes and survival time were analysed. Statistical analysis was carried out using SPSS 10.0 for Windows. Differences of the parametric data of ALT in means were examined by one-way ANOVA. Differences of ALT between two groups were examined by LSD. Differences of the nonparametric data of T bili in means and scores of pathology classification for acute rejection were examined by Kruskal-Willis H test. The correlations between ALT and T bili were analysed by Bivariate. Kaplan-Meier curves were used to demonstrate survival distribution. The log-rank test was used to compare the survival data. RESULTS: There were significant differences in ALT of the five groups (F= 23.164 P= 0.000), and ALT in Dex-SpC group was significantly higher than that in blank control, control, Dex, and SpC groups (P = 0.000), and ALT in SpC group was significantly higher than that in blank control (P= 0.000), control (P= 0.004), and Dex groups (P= 0.02). Results of nonparametric analysis of T bill showed that there were differences in T bill of the five groups (X2= 33.265 P= 0.000). T bili in Dex-SpC group was significantly higher than that in blank control, control, Dex, and SpC groups. T bili in SpC group was higher than that in blank control, control, and Dex groups. There were significant differences in scores of pathology classification for acute rejection in each of the groups (X2= 25.933, P= 0.000). The pathologically more serious acute rejection was found in Dex-SPC group than in other groups. No sign of acute rejection was observed in the blank control group. Slight acute rejection was observed in the control group. Slight-moderate acute rejection was observed in the Dex group. Moderate-acute rejection was observed in the SpC group. Severe-acute rejection was observed in the Dex-SpC group. The survival time in Dex-SpC group was shorter than in other groups (statistic = 11.13, P= 0.011). ALT and T bili were positively correlated (r= 0.747, P= 0.000, two-tailed). CONCLUSION: In order to reduce quantity of blood loss from rats after liver transplantation, only one of ALT or T bili is needed for liver function measurement of rats. Simultaneous injection of apoptotic spleen cells from donors induced by dexamethasone to liver transplantation rats aggravates acute rejection. One important mechanism of aggravation of acute rejection may be that apoptotic cells are not removed in time and that dead cells including apoptotic cells release inflammatory factors.
文摘AIM: To analyze the expression levels of soluble form of CD95, CD95 ligand (sCD95 and SCD95L, respectively) in plasma and CD95 expression on CD3+cells in liver-transplanted recipients with acute rejection (AR). METHODS: Peripheral blood mohonuclear cells (PBMCs) were isolated from 30 clinically liver transplanted recipients. CD95 expression on CD3+ cells was quantitatively measured by two-color fluorescence activated cell sorter (FACS) analysis. Lymphocyte surface phenotypes of CD4, CD8, CD16 and CD56 were determined by flow cytometry. Plasma levels of sCD95 and SCD95L were detected by Enzyme Linked-Immuno-Sorbent Assay (ELISA). The results were compared with that from normal healthy volunteers (n=15 individuals). RESULTS: FACS analysis showed that CD95 expression on CD3+ T cells was significantly increased in liver transplanted recipients with AR compared to that in stable recipients without rejection and infection or healthy individuals who did not undergo transplantation (18 676.93±11 588.34/molecule, 6 848.20±1 712.96/molecule, 6 418.01±2 001.95/molecule, respectively, P<0.01). Whereas no significant difference was seen between liver-transplanted stable recipients and healthy individuals. Furthermore, no significant differences were detected between each group with CD4/CD8 ratio or the percentage of CD16+56+cells. Plasma levels of sCD95 were significantly higher in transplanted recipients with AR compared to that in stable recipients or healthy individuals (391.88±196.00, 201.37±30.30, 148.83±58.25 pg/mL, respectively, P<0.01). In contrast, the plasma levels of sCD95L in liver-transplanted recipients were not significantly different from that in healthy individuals. CONCLUSION: The present results indicate that the increased CD95 expression on CD3+cells and the increased levels of sCD95 in plasma may modify the immunological situation of the recipients after transplantation or represent the ongoing graft rejection.
基金a Grant-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan and Grants-in-aid for Research on HIV/AIDS and Research on Measures for Intractable Diseases from the Ministry of Health, Labor and Welfare of Japan
文摘AIM： TO investigate the incidence and risk factors of late-onset acute rejection （LAR） and to clarify the effectiveness of our immunosuppressive regime consisting of life-long administration of tacrolimus and steroids. METHODS： Adult living donor liver transplantation recipients （n = 204） who survived more than 6 mo after living donor liver transplantation were enrolled. Immunosuppression was achieved using tacrolimus and methylprednisolone. When adverse effects of tacrolimus were detected, the patient was switched to cyclosporine. Six months after transplantation, tacrolimus or cyclosporine was carefully maintained at a therapeutic level. The methylprednisolone dosage was maintained at 0.05 mg/kg per day by oral administration. Acute rejections that occurred more than 6 mo after the operation were defined as late-onset. The median follow-up period was 34 too. RESULTS： LAR was observed in 15 cases （7%） and no chronic rejection was observed. The incidence of hyperlipidemia, chronic renal failure, new-onset post-transplantation diabetes, and deep fungal infection were 13%, 2%, 24%, and 17%, respectively. Conversion from tacrolimus to cyclosporine was required in 38 patients （19%）. Multivariate analysis revealed that a cyclosporine-based regimen was significantly associated with LAR.events happen at a low incidence, supporting the safety and efficacy of the present immunosuppression regimen for living donor liver transplantation.
文摘BACKGROUND:In liver transplantation,acute cellular rejection(ACR)is still a major complication that can lead to mortality.Bile secretion has been considered as a marker of early graft function. METHODS:The study included 41 adults who received living donor liver transplantation(LDLT)at Kyoto University Hospital between April 2007 and February 2008. The patients were stratified according to the presence or absence of ACR.Bile samples were collected from donors once and from recipients every other day for the first 2 weeks after transplantation.Total bile acid(BA)and taurine-conjugated bile acid(TCBA)in bile were measured by magnetic resonance spectroscopy.The recipient/donor (R/D)BA ratio and R/D TCBA ratio were calculated. RESULTS:The ACR group(n=12)showed a greater decrease in BA post-transplantation than the non-ACR group,but this difference was not statistically significant. On both day 7 and day 9 post-transplantation the R/D TCBA was significantly different between the two groups (P=0.038 on day 7 and P=0.036 on day 9).The R/D TCBA ratio≥0.5 on days 7 and 9,and≥0.38 on day 11 post- transplantation were associated with better ACR-free survival. CONCLUSION:The recipient/donor TCBA ratio can be a predictor for ACR after LDLT as early as post- transplantation day 7.
文摘BACKGROUND: Although many human inflammatory and autoimmune diseases were previously considered to be mediated by T helper type 1 (Th1) cells, the recently described Th17 cells play dominant roles in several of these diseases. We and others speculated that allograft rejection after organ transplantation may also involve Th17 cells. Episodes of acute rejection occur in 30% of liver transplants. This study aimed to determine the frequency of circulating Th17 cells in patients who had received liver transplants for benign end-stage liver disease and to identify any association between acute rejection episodes and levels of Th17 cells in the peripheral blood. METHODS: A prospective study compared Th17 cells from 76 consecutive benign end-stage liver disease patients who had undergone orthotopic liver transplantation from 2007 to 2011 with those from 20 age-matched healthy individuals. Peripheral blood samples were collected at different time points within one year after transplant. Blood samples and liver biopsies were also collected at the diagnosis of acute rejection. Percentages of circulating CD4+ IL-17+ cells were measured by flow cytometry The transplant patients were classified into two groups: a rejection group consisting of 17 patients who had an episode of acute rejection, and a non-rejection group comprising the remaining 59 patients with no acute rejection episodes Percentages of circulating Th17 cells were compared between the two groups and controls. RESULTS: The levels of circulating CD4+ IL-17+ T cells in the rejection group were higher during acute rejection than those in the non-rejection group (2.56±0.43% versus 1.79±0.44% P<0.001). The frequency of CD4+ IL-17+ cells in peripheral blood was positively correlated with the rejection activity index (r=0.79, P=0.0002).CONCLUSION: Circulating Th17 cells may be useful as a surrogate marker for predicting acute rejection in liver transplant recipients.
基金supported by a grant from National Basic Research 973 Program of China (No.2009CB522407)
文摘To identify acute renal allograft rejection biomarkers in human serum, two-dimensional differential in-gel electrophoresis （2-D DIGE） and reversed phase high-performance liquid chromatography （RP-HPLC） followed by electrospray ionization mass spectrometry （ESI-MS） were used. Serum samples from renal allograft patients and normal volunteers were divided into three groups： acute rejec- tion （AR）, stable renal function （SRF） and normal volunteer （N）. Serum samples were firstly processed using Multiple Affinity Removal Column to selectively remove the highest abundance proteins. Differentially expressed proteins were analyzed using 2-D DIGE. These differential protein spots were excised, digested by trypsin, and identified by RP-HPLC-ESI/MS. Twenty-two differentially expressed proteins were identified in serum from AR group. These proteins included complement C9 precursor, apolipoprotein A-IV precursor, vitamin D-binding protein precursor, beta-2-glycoprotein 1 precursor, etc. Vitamin D-binding protein, one of these proteins, was confirmed by ELISA in the independent set of serum samples. In conclusion, the differentially expressed proteins as serum biomarker candidates may provide the basis of acute rejection noninvasive diagnosis. Confirmed vitamin D-binding protein may be one of serum biomarkers of acute rejection. Furthermore, it may provide great insights into understanding the mechanisms and potential treatment strategy of acute rejection.
文摘In order to evaluate the applied value of soluble intracellular adhesion molecule-1 （sICAM-l） in acute rejection （AR） following liver transplantation, the expression of sICAM-1 protein was sequentially detected by using ELISA in serum and bile of 43 patients receiving liver transplantation. In AR group, the expression levels of sICAM-1 protein were increased 3 days before and immediately on the establishment of AR diagnosis, and there was significant difference in the expression of bile between AR group and control group （P〈0.01）. After reversion of AR with hormone intensive therapy, there was significant difference in the sICAM-1 protein expression of serum and bile between AR group and control group. It was concluded that the sequential detection of sICAM-1 protein level in serum and bile was a reliable and noninvasive method for the early diagnosis of AR after liver transplantation and was valuable to observe the curative effects of anti-AR therapy.
基金supported by a grant from the National Key Technology R&D Program of China(2008ZX10002-26)
文摘BACKGROUND:The 2009 H1N1 influenza A virus was first identified in April 2009 and rapidly evolved into a pandemic. Recipients of solid-organ transplants have a higher risk for severe infection because of immunosuppression.There are limited reports of 2009 H1N1 influenza in liver transplant recipients,especially in China. METHODS:We present a case of a 48-year-old male liver transplant recipient with 2009 H1N1 influenza A virus.He received therapy for acute rejection after transplantation and was confirmed with H1N1 virus infection. RESULTS:The patient was started on oseltamivir(75 mg, orally twice daily)and had a benign hospital course,with defervescence and resolution of symptoms within 72 hours. The follow-up chest radiograph after discharge was normal. CONCLUSIONS:The 2009 H1N1 influenza in this hospitalized transplant recipient was relatively mild,and prolonged viral shedding was not noted.Oseltamivir can be a valid measure in immunocompromised individuals.
文摘AIMTo investigated the feasibility of using sinusoidal endotheliitis (SE) as a histological marker for liver allograft rejection.METHODSWe compared the histological features of 88 liver allograft biopsies with acute cellular rejection (ACR) and 59 cases with no evidence of ACR. SE was scored as: (1) focal linear lifting up of the endothelial cells by lymphocytes with no obvious damage to adjacent hepatocytes; (2) focal disruption of the endothelial lining by a cluster of subendothelial lymphocytes (a group of > 3 lymphocytes); and (3) severe confluent endotheliitis with hemorrhage and adjacent hepatocyte loss.RESULTSThe sensitivity and specificity of SE was 81% and 85%, respectively. Using SE as the only parameter, the positive predictive value for ACR (PPV) was 0.89, whereas the negative predictive value for ACR (NPV) was 0.75. The correlation between RAI and SE was moderate (R = 0.44, P < 0.001) (Figure 3A), whereas it became strong (R = 0.65, P < 0.001) when correlating SE with the venous endotheliitis activity index only.CONCLUSIONOur data suggest that SE scoring could be a reliable and reproducible supplemental parameter to the existing Banff schema for diagnosing acute liver allograft rejection.
基金Corresponding author:Lena Sibulesky,MD,Associate Professor,Surgeon,Department of Surgery,University of Washington Medical Center,UWMC 1959 NE Pacific St,Box 356410 Seattle,Seattle,WA 98195,United States.lenasi@uw.edu。
文摘BACKGROUND The liver has traditionally been regarded as resistant to antibody-mediated rejection(AMR).AMR in liver transplants is a field in its infancy compared to kidney and lung transplants.In our case we present a patient with alpha-1-antitrypsin disease who underwent ABO compatible liver transplant complicated by acute liver failure(ALF)with evidence of antibody mediated rejection on allograft biopsy and elevated serum donor-specific antibodies(DSA).This case highlights the need for further investigations and heightened awareness for timely diagnosis.CASE SUMMARY A 56 year-old woman with alpha-1-antitrypsin disease underwent ABO compatible liver transplant from a deceased donor.The recipient MELD at the time of transplant was 28.The flow cytometric crossmatches were noted to be positive for T and B lymphocytes.The patient had an uneventful recovery postoperatively.Starting on postoperative day 5 the patient developed fevers,elevated liver function tests,distributive shock,renal failure,and hepatic encephalopathy.She went into ALF with evidence of antibody mediated rejection with portal inflammation,bile duct injury,endothelitis,and extensive centrizonal necrosis,and C4d staining on allograft biopsy and elevated DSA.Despite various interventions including plasmapheresis and immunomodulating therapy,she continued to deteriorate.She was relisted and successfully underwent liver retransplantation.CONCLUSION This very rare case highlights AMR as the cause of ALF following liver transplant requiring retransplantation.
文摘AIM: To investigate the association between interleukin (IL)-10-1082 (G/A) promoter polymorphism and acute rejection (AR) in liver transplant (LT) recipients. METHODS: Two investigators independently searched the Medline, Embase, China National Knowledge Infrastructure, and Chinese Biomedicine Databases. Summary odds ratios (ORs) and 95% CIs for IL-10-1082 G/A polymorphism and AR were calculated in a fixed and a random-effects model as appropriate. RESULTS: This meta-analysis included seven casecontrol studies, which comprised 652 cases of LT recipients in which 241 cases developed AR and 411 cases did not develop AR. Overall, the variant A allele was not associated with AR risk when compared with the wild-type G allele (OR = 0.94, 95% CI: 0.64-1.39). Moreover, similar results were observed when the AA genotype was compared with the AG/GG genotype (OR = 1.05, 95% CI: 0.55-2.02). When stratifying for eth-nicity, no significant association was observed among either Caucasians or Asians. Because only one study was performed in Asian patients, the result of subgroup analysis by ethnicity would not be reliable for Asians. Limiting the analysis to the studies with controls in the Hardy-Weinberg equilibrium, the results were persistent and robust. No publication bias was found in the present study. CONCLUSION: This meta-analysis suggests that IL-10-1082 G/A polymorphism may be not associated with AR risk in LT recipients among Caucasians.
基金supported by grants from the National Key Research and Development Program Funded Projects(2017YFC1103703)National Basic Research Program of China(2015CB554100)National Natural Science Foundation(81870446,81670593and 81900571)。
文摘Background:Translationally controlled tumor protein(TCTP),which has been verified to have a proinflammatory activity,plays an important role in allergy.However,it remains unclear whether TCTP has an impact on the acute rejection(AR)after liver transplantation.Methods:Three protocols were used to delineate the role of TCTP in AR after liver transplantation.First,in rat orthotopic liver transplantation(OLT),the expression of TCTP was measured by enzyme-linked immunosorbent assay(ELISA),real-time PCR,Western blot and immunofluorescence assays.Second,in mixed lymphocyte reaction(MLR),the role of TCTP in lymphocyte proliferation was measured by carboxyfluorescein succinimidyl ester(CFSE)labeling and the impact of TCTP on inflammatory factor release was detected by cytokine arrays.Third,in human OLT,the level of serum TCTP was detected by ELISA,and the relationship between TCTP and model for early allograft function(MEAF)score was assessed by Spearman's correlation.Results:In rat OLT,AR resulted in great harm to allografts,manifesting as deterioration of liver function,increasing inflammatory factors and infiltrating lymphocytes.Meanwhile,TCTP was overexpressed in serum and allografts.Higher level of TCTP was associated with higher rejection activity index(RAI).In an MLR protocol,TCTP knockdown inhibited the proliferation of mixed inflammatory cells and significantly suppressed the release of 15 cytokines and chemokines.In human OLT,the serum TCTP was up-regulated within a week after operation.Additionally,the increasing speed of serum TCTP positively correlated with MEAF scores(r=0.449;P=0.0088).
文摘We report a case of reversible hepatofugal portal flow after auxiliary partial orthotopic liver transplantation (APOLT) from a living donor in this study.On postoperative day 6,continuous hepatofugal portal flow was observed in the grafted liver without portal thrombosis and obstruction of the hepatic vein.Based on histological findings,acute rejection was the suspected cause.The normal portal venous flow was restored after steroid pulse and antithymocyte globulin (ATG) therapies.The patient was discharged on the 30th postoperative day.It was concluded that hepatofugal flow after liver transplantation is a sign of serious acute rejection,and can be successfully treated by anti-rejection therapy.
文摘To study the characteristics of acute rejection after limb allotransplantation, 29 male Sprague Dawley rats were randomly divided into 2 groups, with 15 rats in control group and 14 rats in experimental group. Each rat in control group underwent limb replantation. Each rat in experimental group received limb transplantation from Wistar rat. No immnosuppressive drugs were used after operation. The circulation of the transplanted limb, time and signs of rejection, histopathological changes in the tissues of the limb graft when rejected and survival time of limb grafts were evaluated. In the control group, no signs of rejection were observed, the circulation of each replanted limb was normal, it could survive for a longer time. The experimental group showed clinical signs of rejection (sub dermal edema and erythema) after a mean time of 3.36±1.15 days, and the mean survival time of the allografts was only 7±0.78 days. Histopathological examination showed most violent rejection reaction in skin. It is concluded that with Wistar to SD limb transplantation without use of immunosuppression, rejection of the grafts would occur after a mean time of 3.36±1.15days; the earliest signs of rejection were edema and erythema of the skin, skin being the most representative component of limb graft rejection.
文摘To investigate the imbalance state of helper T lymphocytes （Th） and cytotoxic T lymphocytes （Tc） and the roles of Thl/Th2/Th3 and Tcl/Tc2 cells in renal transplantation rejection, the percentages of these cells in peripheral blood of 24 cases of renal transplantation recipients with acute rejection and the dynamic changes of the CD4/CD8 ratio were determined by flow cytometry analysis, while 30 cases of healthy individuals were set up as controls. In these healthy controls, the percentages of the Thl, Th2 and Th3 cells were （ 10.45 ± 8.15） %, （5.05 ± 4.15） % and （3.90 ± 3.21 ） %, and those of Tcl and %2 cells were （9.83 ± 7.03） % and （4.51 ± 2.17） %, respectively. However, the percentages of Thl and Tcl cells in peripheral blood of the stable recipients after transplantation were （7.29 ± 5.62） % and （7.04 ± 5.15）%, showing definite reduction, while those of Th2, Th3 and Tc2 cells showed significant increase, （ 6.34 ± 5.67） %, （4.94 ± 4.14） % and （ 6.86 ± 4.42） %, respectively. In case of recipients with acute rejection, the percentages of Thl and Tcl cells appeared to be （ 18.55 ± 13.21 ） % and （ 15.84 ± 11.72） %, also showing significant increase, but those of Th2, Th3 and %2 cells appeared to be reduced, （4.19 ± 3.62） %, （3.02 ± 2.83 ） % and （3.88 ± 1.63） %, respectively. Significant differences could be detected among these three groups （ P 〈 0.05）. The CD4/CD8 ratio in cases with acute rejection was higher than those of stable recipients （2.24 ± 0.59 vs 1.95 ± 0.45）, but that of the stable recipients and healthy controls （ 1.98 ± 0.31 ） showed no any significant difference. From the above observation, it is evident that imbalance between Thl, Th2 and Th3 with Tcl and Tc2 cells may exist after renal transplantation and probably, the im- mune imbalance may be induced through the secretion of cytokines INF-γby Thl or Tcl cells , Ⅱ-4 by Th2 and Tc2 cells and TGF-β by Th3.
基金Hainan Provincial Natural Science Foundation of China(No.820QN404)Project of the Second Affliated Hospital of Hainan Medical University(2019)。
文摘Objective:To explore the expression profile of miRNA in peripheral blood of patients with acute T cell mediated rejection after kidney transplantation.Method:4 patients with acute T cell mediated rejection(TCMR)after kidney transplantation were collected as experimental group.Meanwhile,4 patients under stable condition after kidney transplantation were collected as control group.The elbow blood was taken from two groups.The next generation sequencing was used to study miRNA libraries.Then,they were analyzed of variance by R language software.Results:14 miRNAs were differently expressed in the experimental group and control group,including 5 up-regulated miRNAs(P<0.05)and 9 down-regulated miRNAs(P<0.05).Conclusions:Peripheral blood miRNAs expression variations might be ideal biomarkers and reveal mechanisms for acute TCMR.
基金supported in part by a grant from the National Nature Science Foundation of China(30972923)
文摘BACKGROUND： Acute cellular rejection（ACR） after liver transplantation（LT） is one of the most common problems faced by transplant recipients in spite of advances in immunosuppressive therapy. Recently, clinical trials reported that ursodeoxycholic acid（UDCA） reduced the incidence of ACR significantly.However, others have shown contradictory conclusion. Therefore,we performed a meta-analysis of rigorous randomized controlled trials（RCTs） to determine the efficacy of UDCA in reducing ACR after LT.DATA SOURCES： All RCTs that evaluated efficacy of UDCA as an adjuvant treatment to prevent ACR after LT were searched from PubMed/MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ScienceDirect databases and Web of Science（from January 1981 to March 2012）. There was no language limitation in these searches. Relevant abstracts of international meetings were also searched. References of each included study were searched manually.RESULTS： A total of 234 patients from four high-quality RCTs（Jadad score 4 to 5） were included in this meta-analysis.Prophylactic use of UDCA did not decrease the incidence of ACR（RR： 0.94, 95% CI： 0.77-1.16, P0.05）, steroid-resistant rejection（RR： 0.77, 95% CI： 0.47-1.27, P0.05） and the number of patients with the multiple episodes of ACR（RR： 0.60, 95% CI：0.28-1.30, P0.05）. Different intervention programs（high-dose vs low-dose UDCA; early vs delayed UDCA treatment） also did not alter the outcomes.CONCLUSIONS： UDCA, as an adjuvant treatment, was not ableto prevent ACR and steroid-resistant rejection after LT. Further trials should be done to determine whether higher dose of UDCA will be beneficial.
