Effect of operation-synchronizing transfusion of apoptotic spleen cells from donor rats on acute rejection of recipient rats after liver transplantation

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.

Hepatofugal Portal Flow Associated with Acute Rejection in Living-donor Auxiliary Partial Orthotopic Liver Transplantation:A Report of One Case and Literature Review

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.

Markers of acute rejection and graft acceptance in liver transplantation

The evaluation of the immunosuppression state in liver transplanted patients is crucial for a correct posttransplant management and a major step towards the personalisation of the immunosuppressive therapy. However, current immunological monitoring after liver transplantation relies mainly on clinical judgment and on immunosuppressive drug levels, without a proper assessment of the real suppression of theimmunological system. Various markers have been studied in an attempt to identify a specific indicator of graft rejection and graft acceptance after liver transplantation. Considering acute rejection, the most studied markers are pro-inflammatory and immunoregulatory cytokines and other proteins related to inflammation. However there is considerable overlap with other conditions, and only few of them have been validated. Standard liver tests cannot be used as markers of graft rejection due to their low sensitivity and specificity and the weak correlation with the severity of histopathological findings. Several studies have been performed to identify biomarkers of tolerance in liver transplanted patients. Most of them are based on the analysis of peripheral blood samples and on the use of transcriptional profiling techniques. Amongst these, NK cell-related molecules seem to be the most valid marker of graft acceptance, whereas the role CD4+CD25+Foxp3+ T cells has still to be properly defined.

Early plasmapheresis and rituximab for acute humoral rejection after ABO-compatible liver transplantation

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.

Correlation of CD95 and soluble CD95 expression with acute rejection status of liver transplantation

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.

Late-onset acute rejection after living donor liver transplantation

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.

Clinical factors affecting rejection rates in liver transplantation

With improvements in survival, liver trans- plant recipients now suffer more morbidity from long-term immunosuppression. Considerations were given to develop individualized immunosuppression based on their risk of re- jection. METHOD： We retrospectively analyzed the data of 788 liver transplants performed during the period from October 1991 to December 2011 to study the relationship between acute cel- lular rejection （ACR） and various clinical factors. RESULTS： Multivariate analysis showed that older age （P=0.04, OR=0.982）, chronic hepatitis B virus infection （P=0.005, OR= 0.574）, living donor liver transplantation （P=0.02, OR=0.648） and use of interleukin-2 receptor antagonist on induction （P〈0.001, OR=0.401） were associated with fewer ACRs. Patients with fulminant liver failure （P=.004, OR=4.05） were more likely to develop moderate to severe grade ACR. CONCLUSIONS： Liver transplant recipients with older age, chronic hepatitis B virus infection, living donor liver trans- plantation and use of interleukin-2 receptor antagonist on in- duction have fewer ACR. Patients transplanted for fulminant liver failure are at higher risk of moderate to severe grade ACR. These results provide theoretical framework for developing individualized immunosuppression.

Is biliary bile acid a good predictor for acute cellular rejection in living donor liver transplantation?

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.

The Role of sICAM-1 Detection in the Diagnosis of Acute Rejection Following Liver Transplantation

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.

Novel H1N1 influenza A virus infection in a patient with acute rejection after liver transplantation

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.

Translationally controlled tumor protein exerts a proin?ammatory role in acute rejection after liver transplantation

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).

Efficacy of ursodeoxycholic acid as an adjuvant treatment to prevent acute cellular rejection after liver transplantation: a meta-analysis of randomized controlled trials

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.

The diagnostic role of heat shock protein 70 in acute rejection after pancreatioduodenal transplantation in rats

Objective To explore the diagnositc role of heat shock protein ( HSP) 70 in acute rejection after pancreatioduodenal transplantation in rats. Methods Groups of Wistar rats underwent total pancreatioduodenal transplantation from allogeneic SD or syngeneic Wistar rats. The grafts were harvested on the posttransplantation day 3,5 and 7 and were used to detect the expression of HSP70 by immunohistochemistry and Western Blotting quantitative methods. The correlation between HSP70 expression and pathological findings was observed. Results The level of HSP70 in the isografts did not change greatly( P 】 0.05); the level of HSP70 in the allografts was increased progressively on the posttransplantation day3, 5 and 7 ( P 【 0.01). There was a significant correlation between HSP70 and pathological score in the allograft group (P 【 0.01, r = 0.934). Conclusion HSP70 involved in pancreas allograft rejection and could be useful for early diagnosis of acute rejection following pancreas transplantation. 8 refs,2 tabs.

Gene transfer of huCTLA4-Ig to inhibit the acute rejection of liver allograft in rats

To observe the effect of gene transfer of huCTLA4-Ig to inhibit the acute rejection of liver allograft in rats.Methods With AdEasy vector system,the recombinant adenovirus containing huCTLA4-Ig gene was constructed.Using ex vivo gene transfer technique,exogenous gene was introduced to the liver graft during cold preservation and expressed locally in the graft.The effect of inhibition of acute rejection and inducing liver graft tolerance was observed.Results No recipients in group A (without any treatment,n=5) or group B (treated with Ad-GFP,n=4) died within 3 weeks after transplantation and severe acute rejection (massive periportal infiltration,endothelilitis,damage to biliary epithelium and severe tissue destruction) was confirmed pathologically in the graft.In contrast,all recipients in group C (treated with Ad-huCTLA4-Ig,n=5) achieved long-term liver allograft survival (>150 days).Histological examination of Ad-huCTLA4-Ig transduced allografts demonstrated a mild to moderate periportal inflammation and mild injury to liver graft on day 8 posttransplant.A mild mononuclear infiltration was observed;however,there was complete preservation of the bild ducts and no evidence of vascular injury on day 150 posttransplant.The mean IL-2 concentration in serum was (362.09±45.84) ng/L at day 1 pretransplant.In control animals (groups A and B),serum IL-2 concentration was elevated to a high level within 7 days posttransplant,which was about 1.5 to 2.5 times as much as that before transplant.In contrast,in huCTLA4-Ig-treated animals (groups C),IL-2 concentration in serum was maintained at a relative low level,which was near or less than that before transplant (P<0.01).Conclusion Using ex vivo gene transfer technique,huCTLA4-Ig gene can be introduced to the liver graft during cold preservation.The modified graft can express and excrete immunoregulatory protein locally,which can suppress acute alloimmune response and is responsible for prolongation of graft survival without using routine immunosuppressive drugs.These findings provide some experimental evidence that gene delivery of sequences encoding immunoregulatory proteins can be applied to clinical liver transplantation for inhibiting the acute alloimmune response and achieving graft tolerance.7 refs,2 tabs.

Immunomodulatory effects of mesenchymal stem cells derived from adipose tissues in a rat orthotopic liver transplantation model

BACKGROUND: Acute rejection after liver transplantation is usually treated with large doses of immunosuppressants with severe toxic and side-effects, so it is imperative to find a safe and effective method for preventing and treating rejection. This study was designed to confirm the immunomodulatory effects of rat mesenchymal stem cells (MSCs) in vitro and investigate the tolerogenic features in a rat model of allogeneic liver transplantation. METHODS: MSCs were isolated from adipose tissue of Sprague-Dawley (SD) rats and cultured. In vitro, MSCs were added into a mixed lymphocyte culture (MLC) system to study the inhibitory effects of MSCs on the proliferation of T lymphocytes in Wistar rats. By using SD and Wistar rats as liver donors and recipients, an orthotopic liver transplantation model was established and the rats were divided into a MSC-treated group and a blank control group. On postoperative day 7, all rats were sacrificed, and the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), interleukin-2 (IL-2) and interleukin-10 (IL-10) were measured. The pathological changes of liver tissue and apoptosis of hepatocytes were also assessed. RESULTS: In in vitro MLC, T lymphocyte proliferation in Wistar rats was significantly inhibited by 48.44%. In the MSC-treated group, the levels of ALT, AST, TBIL, IL-2 and IL-10 were 134.2 +/- 45.0 U/L, 162.5 +/- 30.5 U/L, 30.6 +/- 5.4 mu mol/L, 187.35 +/- 18.26 mu g/L and 193.95 +/- 37.62 mu g/L, and those in the blank control group were 355.6 +/- 54.3 U/L, 296.4 +/- 71.2 U/L, 145.7 +/- 28.6 +/- mol/L, 295.73 +/- 57.15 mu g/L and 75.12 +/- 11.23 mu g/L, respectively, with statistically significant differences (P<0.05). Pathological examination revealed that the rejection in the MSC-treated group was clearly alleviated compared with that in the blank control group. TUNEL indicated that the apoptosis of hepatocytes in the MSC-treated group was milder than that in the blank control group (P<0.05). CONCLUSION: Adipose-derived MSCs clearly inhibit recipient-derived T lymphocyte proliferation in MLC and significantly alleviate acute rejection following orthotopic liver transplantation in rats.

Increase of peripheral Th17 lymphocytes during acute cellular rejection in liver transplant recipients

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.

Hepatocellular carcinoma recurrence after acute liver allograft rejection treatment: A multicenter European experience

Background:During the last decades,several risk factors for the recurrence of hepatocellular carcinoma(HCC)after liver transplantation(LT)have been investigated.However,the impact of two important drivers of oncogenesis,namely the immunosuppression and the treatment of acute cellular rejection(ACR)have been marginally addressed.This study aimed at investigating the impact of ACR treatment on the incidence of tumor recurrence in a large European HCC-LT population.Methods:Seven hundred and eighty-one adult patients transplanted between February 1,1985 and June 30,2016 were retrospectively analyzed.After propensity score match,116 patients treated for ACR using steroid boluses were compared with 115 patients who did not present any ACR or a histologic but clinical irrelevant ACR.Results:Steroid boluses treated patients had a 18-fold higher overall incidence of HCC recurrence than those non-treated patients(16.4%vs.0.9%;P<0.0001).At multivariate Cox regression analysis,steroid boluses used to treat ACR were an independent risk factor for HCC recurrence(HR=14.2;95%CI:1.8–110.4;P=0.010).Conclusions:The decision to treat ACR as well as to reinforce immunosuppression load should be cautiously taken in view of the presented results.Prospective studies are needed to further elucidate the clinical impact of immunosuppression on HCC recurrence after transplantation.

Mechanism of Immune Hyporesponsiveness Induced by Recipient-derived Immature Dendritic Cells in Liver Transplantation Rat

Objective To investigate the mechanism of immune hyporesponsiveness induced by donor-antigen- unloaded recipient-derived immature dendritic cell （imDC） of liver grafts in rats. Methods Forty Sprague-Dawley rats （donor） and forty male Wistar rats （recipient） were randomly divided into 4 groups： control, cyclosporine A （CsA）, mature DC （mDC）, and imDC groups respectively, with 10 donor rats and 10 recipient rats in each group. Recipient rats in CsA group were treated with 10 mg-kg-~＇d-I CsA starting day 2 after the transplantation. Recipients in the mDC or imDC groups were given Wistar rat derived mDCs （1 × 10^6/rat） or imDCs （1 × 10^6/rat） via dorsal vein of the penis respectively 1 day before the transplantation. In each group, 5 recipients were kept for determination of survival time and the other 5 rats were executed at day 10 after transplantation. Blood samples were collected for the measurement of serum alanine aminotransferase （ALT）, total bilirubin （TBIL）, interleukin 2 （IL-2）, interferon gamma （IFN-γ）, IL-4, and IL-10 levels. Liver tissue was harvested for HE staining and acute rejection evaluation. Expression levels of Fas-L/Fas in the grafts were detected by immunohistochemical staining; andWestern blot was used to detect the expression level of Scurfm. Results The survival time of CsA and imDC groups was significantly longer than that of control and mDC groups （all P〈0.05）. The levels of serum ALT and TBIL in the control group （2072.20±217.93 IU/L and 147.42±22.02pmol/L） and mDC group （2117.00±285.13 IU/L and 141.58±20.82 pmol/L） were significantly higher than those in the CsA group （59.68±13.48 IU/L and 15.40±2.13 pmol/L） or imDC group （50.80±9.63 IU/L and 14.44±3.49 pmol/L） （all P〈0.05）. In the CsA and imDC groups, the levels of IL-2 （22.52±3.75 pg/mL and 22.12±3.90 pg/mL） and IFN-γ （309.20±25.19 pg/mL and 321.00±21.64 pg/mL） were significantly lower, but the levels of IL-4 （297.60±25.07 pg/mL and 277.00±22.47 pg/mL） and IL-10 （1226.00±140.49 pg/mL and 1423.00±106.39 pg/mL） were higher than those of the control （IL-2：147.78±12.80 pg/mL, IFN-γ： 1758.60±106.22 pg/mL, IL-4：17.40±4.77pg/mL, IL-10： 81.00＋ 9.47 pg/mL） and mDC groups （IL-2：142.34±9.29 pg/mL, IFN-7：1835.00±82.63 pg/mL, IL-4： 15.60＋ 3.96 μg/mL, IL-10： 68.80± 11.23 pg/mL） （all P〈0.01）. The expression level of Scurfin protein on CD4＋CD25 ＋ T cells of the imDC group （1.34±0.29） was significantly higher than that in the control （0.72±0.13）, CsA （0.37±0.11）, and mDC groups （0.78±0.17） （all P〈0.05）.

HLA variants related to primary sclerosing cholangitis influence rejection after liver transplantation

AIM: To investigate influence of human leukocyte antigen (HLA) and killer immunoglobuline-like receptor (KIR) genotypes on risks of acute rejection (AR) after liver transplantation (LTX).

Sinusoidal endotheliitis as a histological parameter for diagnosing acute liver allograft rejection

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 &#x0003e; 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 &#x0003c; 0.001) (Figure 3A), whereas it became strong (R = 0.65, P &#x0003c; 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.