New developments in renal transplant pathology

The renal transplant biopsy plays a central role in the diagnosis of renal allograft dysfunction; in particular in differentiating immune-mediated rejection from various infective, ischaemic and toxic pathologies. Recent advances have been made in refining the histological criteria for rejection diagnosis. The Banff’97 classification of renal allograft pathology has gained almost universal acceptance. In this classification, acute rejection is divided into three main types, tubulointerstitial, vascular and severe vascular, that differ in response to anti-rejection therapy and long-term prognosis. There remain, however, a number of challenges; interpretation of biopsies showing borderline changes, the diagnosis of humoral rejection and differentiating rejection from interstitial nephritis associated with viral infections present specific problems. There are potential applications for new molecular and immunohistochemical techniques in these areas. Other challenges arise from the application of the Banff classification. Recent validation studies have indicated that the reproducibility of some Banff criteria is low and that there are a number of histological features, not included in the Banff schema, that may be useful in rejection diagnosis.New roles for the transplant biopsy are developing in the management of patients with stable graft function, as indicated by measurement of serum creatinine. Protocol biopsies performed at regular intervals in the early post-transplant period may be used to predict subsequent development of chronic allograft nephropathy, the major cause of graft loss. The interpretation of these biopsies may be refined using morphometric techniques and immunohistochemistry for cytokines and matrix components. Protocol biopsies may also be used to diagnose sub-clinical rejection, and early evidence indicates that treatment of these histological rejections improves long-term graft outcome. The role of the transplant biopsy will continue to evolve with greater use of organs from marginal donors, improved understanding of the processes of graft injury and fibrosis, and the introduction of new immunosuppressive regimens.     

The clinical and pathologic implications of plasmacytic infiltrates in percutaneous renal allograft biopsies

Plasmacytic infiltrates in renal allograft biopsies are uncommon and morphologically distinctive lesions that may represent variants of acute rejection. This study sought significant clinical and pathologic determinants that might have influenced development of these lesions and assessed their prognostic significance. Renal allograft biopsies (n = 19), from 19 patients, with tubulointerstitial inflammatory infiltrates containing abundant plasma cells, composing 32 +/- 8% of the infiltrating mononuclear cells, were classified using Banff '97 criteria. Clonality of the infiltrates was determined by immunoperoxidase staining for kappa and lambda light chains and polymerase chain reaction for immunoglobulin heavy-chain gene rearrangements, using V(H) gene framework 3 and JH consensus primers. In situ hybridization for Epstein-Barr virus encoded RNA (EBER) was performed in 17 cases. The clinical features, histology, and outcome of these cases were compared with kidney allograft biopsies (n = 17) matched for time posttransplantation and type of rejection by Banff '97 criteria, with few plasma cells (7 +/- 5%). Sixteen of 19 biopsies (84%) with plasmacytic infiltrates had EBER-negative (in 14 cases tested) polyclonal plasma cell infiltrates that were classifiable as acute rejection (types 1A [4], 1B [10], and 2A [2]). These biopsies were obtained between 10 and 112 months posttransplantation. Graft loss from acute and/or chronic rejection was 50% at 1 year and 63% at 3 years, and the median time to graft failure was 4.5 months after biopsy. There was no significant difference in overall survival or time to graft failure compared with the controls. Three of 19 biopsies (16%) had EBER-negative polyclonal plasmacytic hyperplasia, mixed monoclonal and polyclonal polymorphous B cell hyperplasia, and monoclonal plasmacytoma-like posttransplantation lymphoproliferative disease (PTLD) and were obtained at 17 months, 12 weeks, and 7 years after transplantation, respectively. Graft nephrectomies were performed at 1, 19, and 5 months after biopsy, respectively. Plasmacytic infiltrates in renal allografts comprise a spectrum of lesions from acute rejection to PTLD, with a generally poor prognosis for long-term graft survival.     

Arcuate and interlobular phlebitis in renal allografts

Intimal arteritis in the renal allograft has a well-documented adverse effect on graft outcome. In contrast, venulitis is currently considered an innocuous finding, based largely on observations of thin-walled intermediary venules. Arcuate and interlobular veins have not been studied specifically. These veins have well-developed muscular walls, and inflammation at this level (phlebitis) could significantly alter renal hemodynamics. We studied the clinicopathologic correlates of arcuate and interlobular phlebitis in 31 renal allograft biopsy specimens. Phlebitis was seen in conjunction with borderline changes suggestive of acute cellular rejection (13 cases), or acute rejection Banff grade 1A (7 cases), Banff grade 1B (6 cases), Banff grade 2A (4 cases), and Banff grade 2B (1 case). Clinical follow-up (average 323 +/- 460 days) showed no adverse effects of phlebitis as judged by temporal changes in serum creatinine and the grade of chronic allograft nephropathy in follow-up biopsies. Thus it appears that arcuate and interlobular phlebitis in allograft biopsy specimens does not add prognostic information beyond that provided by conventional Banff criteria. However, this lesion frequently coexists with changes suggestive or diagnostic of acute cellular rejection, and intimal arteritis may be seen concurrently in up to 16% of cases.     

Histologic findings in protocol biopsies of transplanted kidneys

Fourty eight patients with cadaveric kidney allografts treated by cyclosporin A (CSA) or tacrolimus (FK506) underwent protocol graft biopsies at 1, 3 and 12 months after transplantation, and 110 biopsy specimens were obtained. Histologic diagnosis was made according to the Banff scheme. The main cause of the graft instability at 1 and 3 months was acute clinical rejection, these biopsies showed all known histological patterns of tubulointersticial and vascular rejection. Acute tubular nephropathy was found in 13% and borderline changes or nephrotoxicity in 8.7% of instable grafts. Specifically, we focused on the occurRence of subclinical rejection and toxic reactions in stable renal allografts. Of these, 36.1% showed histological patterns of acute tubulointersticial and vascular rejection. The Banff score of subclinical rejection was significantly lower than in clinically apparent rejection. CSA and tacrolimus nephrotoxicity were seen in 14.2%, 19.5% and 27.2% of specimens at 1, 3 and 12 months, respectively. In over one half of the identified cases of nephrotoxicity neither increased level of immunosuppression nor features of allograft dysfunction were found. At 12 months, 45.5% of specimens showed mild chronic transplant nephropathy and 18.1% moderate chronic transplant nephropathy. Normal morphology was found in 36.4% of biopsies. We found a high prevalence of subclinical rejection and nephrotoxicity in the studied cohort. We conclude that protocol biopsy is a reliable method in the diagnosis of clinically silent, as well as clinically apparent, disorders of the transplanted kidney.     

Renal medullary changes in renal allograft recipients with raised serum creatinine

OBJECTIVE: To test the hypothesis that the renal medulla may reflect rejection related changes and thus have a predictive value in the assessment of acute renal allograft rejection or chronic graft damage. METHODS: 75 post-transplant biopsies from 57 patients were scored according to the Banff 1997 scheme. The biopsies with adequate cortical and medullary tissue (n = 23) were selected and medullary tissues were reviewed for rejection related lesions except intimal arteritis. Chronic damage was determined by image analysis depending on periodic acid-methenamine silver (PAMS)-Masson trichrome (MT) staining. Medullary and cortical changes were compared. RESULTS: Interstitial inflammation and tubulitis were more frequent and severe in the cortex (p<0.001). Medullary tubulitis was associated with intimal arteritis (p = 0.003, r = 0.598). Medullary interstitial inflammation (n = 8) and tubulitis (n = 4) were associated with cortical borderline changes (n = 5) or allograft rejection (n = 3). The sensitivity, specificity, and positive and negative predictive values of medullary inflammatory changes in predicting cortical allograft rejection were 43%, 69%, 37%, and 73%, respectively. A significant association was observed between medullary MT-SAP and cortical PAMS-SAP values (p = 0.02, R(2) = 0.23). CONCLUSIONS: Acute rejection related lesions are more common and severe in the cortex, and the renal medulla does not sufficiently reflect cortical rejection. The positive and negative predictive values of medullary changes for allograft rejection are low, and medullary inflammation is not a reliable indicator of allograft rejection. Increased medullary fibrosis is correlated with chronic cortical damage.     

Diagnosis of acute humoral rejection using immunofluorescence in renal allograft biopsies- one step towards better understanding!

Immunofluorescence (IF) studies are important diagnostic tool in understanding pathogenesis involved in graft injury. Acute humoral rejection (AHR) associated with circulating donor-specific cytotoxic antibodies, is a poor prognosticator for graft survival. It can be diagnosed by staining for C4d antibody using indirect IF technique. C4d staining required to diagnose AHR was made mandatory for reporting renal allograft biopsies in 7th Banff conference. We present 2 years experience of IF studies using C4d polyclonal antibody on 546 renal allograft biopsies belonging to two groups of patients; 464 from group A (tolerance induction protocol) and 82 from group B (controls). We observed C4d focal positivity in 4 (0.9%) biopsies from group A and 4 (4.9%) from group B. We conclude that it is advisable to collect simultaneous core biopsy samples for IF studies and light microscopy to give better definition of allograft injury and thereby support in clinical management.     

A neural network approach to the biopsy diagnosis of early acute renal transplant rejection

AIMS: To develop and test a neural network to assist in the histological diagnosis of early acute renal allograft rejection. METHODS AND RESULTS: We used three sets of biopsies to train and test the network: 100 'routine' biopsies from Leicester; 21 selected difficult biopsies which had already been evaluated by most of the renal transplant pathologists in the UK, in a study of the Banff classification of allograft pathology and 25 cases which had been classified as 'borderline' according to the Banff classification in a review of transplant biopsies from Oxford. The correct diagnosis for each biopsy was defined by careful retrospective clinical review. Biopsies where this review did not provide a clear diagnosis were excluded. Each biopsy was graded for 12 histological features and the data was entered into a simple single layer perception network, designed using the MATLAB neural network toolbox. Results were compared with logistic regression using the same data, and with 'conventional' histological diagnosis. If the network was trained only with the 100 'routine' cases, its performance with either of the other sets was poor. However, if either of the 'difficult' sets was added to the training group, testing with the other 'difficult' group improved dramatically; 19 of the 21 'Banff' study cases were diagnosed correctly. This was achieved using observations made by a trainee pathologist. The result is better than was achieved by any of the many experienced pathologists who had previously seen these biopsies (maximum 18/21 correct), and is considerably better than that achieved by using logistic regression with the same data. CONCLUSION: A neural network can provide a considerable improvement in the diagnosis of early acute allograft rejection, though further development work will be needed before this becomes a routine diagnostic tool. The selection of cases used to train the network is crucial to the quality of its performance. There is scope to improve the system further by incorporating clinical information. Other related areas where this approach is likely to be of value are discussed.     

Evidence for the early involvement of interleukin 17 in human and experimental renal allograft rejection

Inflammatory processes can stimulate renal epithelial cells to release cytokines, chemoattractants and matrix proteins into the interstitium, thus contributing to interstitial injury during acute allograft rejection. To test the role of interleukin 17 (IL-17) in this process, cultured human renal epithelial cells (hRECs) were first established and treated with or without human IL-17 (hIL-17) for 2, 4, 8 and 10 h in vitro. Significant elevations of IL-6 and IL-8 levels were noted in the supernatants in a dose-dependent and time-dependent manner, as also for IL-6 mRNA expression. Secondly, using a rat acute allograft rejection model, the correlation between IL-17 expression and histopathological changes was serially studied. The results demonstrated that increased expression of IL-17 protein on infiltrating mononuclear cells (MNCs) was detectable on day 2. This corresponds to the borderline change of acute rejection according to the Banff classification, and it increased progressively to day 5. Serial study of IL-6, IL-8 and IL-17 mRNA expression of the renal allograft confirmed IL-17 mRNA expression in the allograft early on post-transplant day 2, whereas IL-6 and IL-8 expression started on day 3. Thirdly, IL-17 expression was observed in human renal allograft and urinary sediment. IL-17 protein expression was found in human subclinical (borderline) rejection renal allograft biopsy tissue and none in biopsy tissue not showing any evidence of rejection. There was also a 100% detectable rate of IL-17 mRNA expression in the MNCs of urinary sediment of patients with subclinical borderline rejection. These results demonstrate that hRECs exposed to IL-17 can produce inflammatory mediators with the potential to stimulate early alloimmune responses, which may also serve to give warning of acute renal allograft rejection.     

Acute rejection and graft survival in renal transplanted patients with viral diseases.

Transplanted patients are susceptible to viral infections; thus, the aim of this study was to evaluate the features of acute rejections and the outcome of the renal graft in transplanted patients with herpes virus diseases. Renal biopsies from 30 renal transplanted patients undergoing early acute rejection (type IA and IB according to the Banff 97 classification) were evaluated. In total, 15 of these patients experienced cytomegalovirus (CMV) or Epstein-Barr virus disease within the first year following transplantation (group I) and 15 patients showed no evidence of viral infection (group II). No significant differences between the groups in terms of age, male/female ratio, living/cadaveric donor ratio, cold ischemia time, HLA A-B matching, pretransplant panel reactive antibody test, occurrence of post-transplant tubular necrosis, plasma levels of cyclosporin A and mean percent increase of serum creatinine at the time of the biopsy were observed. In group I biopsies, the mean number of interstitial plasma cells, as well as the mean number of CD79a-positive cells (B lymphocytes and plasma cells) was significantly higher than in group II (P<0.01 and <0.01, respectively). There was a positive correlation between the number of infections and the number of plasma cells (P<0.05). In transplanted patients, CMV can trigger the formation of anti-endothelial cell antibodies, which have been proposed to play a role in antibody-mediated rejections. We investigated whether a deposition of C4d, a marker of antibody-mediated reactions, was present in renal peritubular capillaries. In group I C4d deposition was found in five cases, while in group II it was not observed (P<0.05). In group I, 7/15 patients developed chronic allograft nephropathy vs 1/15 patients in group II (P<0.05). The estimated 1-, 5- and 8-year cumulative graft survival rates were 80, 66 and 57%, respectively, in group I, while in group II the estimated 8-year cumulative survival rate was 100% (P<0.05). In conclusion, acute rejection biopsies of patients with viral infections displayed plasma cell infiltrates and, in several cases, C4d deposition. Our study suggests a role of B lymphocytes in the pathology of these rejections and confirms the association between viral infections and poor graft survival.     

Peritubular capillary C4d deposition in chronic allograft dysfunction

Peritubular capillary (PTC) C4d staining represents a marker for acute humoral rejection, however, the impact of positive staining on chronic allograft dysfunction has received little attention. Ninety-three renal allograft biopsies from 93 patients were selected from a total of 174 renal allograft biopsies, which were obtained 6 months or more after transplantation (median: 89 months). Fresh frozen renal tissue was stained with monoclonal antibody against C4d. Sixteen of 93 biopsies showed C4d staining in PTC. C4d staining was positive in 40% of acute rejection cases (n=15) and 21% of chronic rejection cases (n=24). When the samples were divided according to C4d positivity, the C4d (+) group had a higher proportion of acute rejection than the C4d (-) group. However, no significant difference was observed between the two groups in terms of the prevalence of chronic rejection. Degrees of histological injury including tubulitis, interstitial inflammation and interstitial fibrosis were not significantly different between C4d (+) and C4d (-) groups. However, the 2-year graft survival rate after biopsy was lower in the C4d (+) group than in the C4d (-) group (24.8% versus 59.0%, p=0.1255). C4d staining in PTC is associated with late acute rejection, but not with chronic rejection based on conventional morphologic criteria in patients with chronic allograft dysfunction.     

Diagnosis of early acute renal allograft rejection by evaluation of multiple histological features using a Bayesian belief network.

BACKGROUND AND AIMS: The development of the Banff classification of renal transplant pathology has allowed the standardisation of approaches to transplant biopsy histology and reduced interobserver and interdepartmental variation. The usefulness of the Banff classification in the diagnosis of acute rejection has previously been tested by sending sections from 21 "difficult" biopsies to almost all of the renal transplant pathologists in the UK. Although the Banff classification improved reproducibility, the accuracy of diagnosis of early acute rejection was unchanged from the "conventional" approach. Perhaps this is because in making a diagnosis of acute rejection, the Banff classification uses only two features: tubulitis and intimal arteritis. To include more features on a systematic basis would be laborious for a human observer. Therefore, a Bayesian belief network was developed for this task. METHODS: The network was initialised with observations from 110 transplant biopsies. Its performance was then tested on 21 biopsies that had been seen by 37 different renal transplant pathologists in an earlier study. These biopsies had been selected to represent histologically difficult problems but, in retrospect, they all had clear diagnoses of rejection or non-rejection on clinical grounds. RESULTS: Using the Bayesian belief network, a relatively inexperienced pathologist made 19 of 21 correct diagnoses, better than had been achieved by any of the pathologists who had seen the same sections previously (17 of 21), and considerably better than the average proportion of correct diagnoses provided by all 37 renal transplant pathologists (65%). Application of the system by a second pathologist produced a tendency to overdiagnosis of acute rejection, illustrating the consequences of interobserver variation. CONCLUSIONS: In the diagnosis of acute rejection, further useful information can be extracted from features that are currently not considered in the Banff classification. Integration of data by a computer can give a more reliable diagnosis of early acute rejection, but routine application will require the development of a more sophisticated system that can also accommodate clinical data, perhaps one that can continue to "learn" as more data are entered.     

494例次移植肝穿刺活检病理组织学分析

目的 通过对354例(494例次)移植肝穿刺活检组织进行病理分析，观察移植肝的组织学变化，探讨其出现肝功能不全的原因。方法 移植肝穿刺活检组织经10％中性福尔马林固定，快速石蜡连续切片，常规HE染色。部分病例做VG、Masson、PAS、网状纤维组织化学和免疫组织化学染色，抗体为HBsAg、HBcAg、HcVAg、CMV、CD8、CD4、CK19。对排斥反应病例，依照国际统一的BANFF标准进行急性排斥反应分级，应用排斥活动指数(RAI)进行排斥反应程度评分。结果 急性细胞性排斥反应最常见，180例(50．85％)，慢性排斥反应11例(3．11％)，再灌注缺血损伤20例(5．65％)，胆汁淤滞及急慢性小胆管炎64例(18．08％)，药物性肝损害18例(5．08％)，移植肝无功1例(0．28％)，CMV感染24例(6．78％)，乙肝病毒再感染及乙肝复发27例(7．63％)，丙型肝炎复发2例(0．56％)，原发性硬化性胆管炎复发1例(0．28％)，难以诊断6例(1．69％)。结论 移植肝穿刺活检对移植术后并发症的诊断及选择治疗方案具有重要价值。     

T-cell/periodic acid-Schiff stain: a useful tool in the evaluation of tubulointerstitial infiltrates as a component of renal allograft rejection

Distinguishing between tubulitis and tubulointerstitial mononuclear cell infiltrates and determining the severity of tubulitis are critical components of diagnosing and grading renal allograft rejection using the 1993 Banff schema, the revised 1997 Banff schema, or the Cooperative Clinical Trials in Transplantation grading system. We describe a novel staining method, the T-PAS stain (CD3 and periodic acid-Schiff), which removes some of the subjectivity in the evaluation of tubulointerstitial infiltrates in renal allograft biopsies. The method simply combines two routine stains, immunoperoxidase staining for T cells (CD3) and periodic acid-Schiff (PAS) staining for tubular basement membrane, on the same section.     

肾移植后急性体液排斥反应：5年同一机构296例随访*

背景：肾移植后急性体液排斥反应虽然发生率不高,但对移植物功能恢复可造成严重影响,是移植物早期丢失的主要原因。 目的：分析肾移植后急性体液排斥反应早期诊断和防治的意义。 方法：选择接受肾移植后规律随访的受者296例,其中移植前群体反应性抗体阳性受者26例,阴性受者270例。酶联免疫吸附试验动态监测肾移植受后外周血中的群体反应性抗体和供者特异性抗体,免疫组织化学染色观察穿刺活检组织中C4d的沉积及浸润淋巴细胞表面分子标记,按Banff 2005标准结合临床相关指标诊断急性体液排斥反应。 结果与结论：26例移植前群体反应性抗体阳性受者中6例(23%)移植后发生了急性体液排斥反应,270例阴性受者中19例(7%)发生了急性体液排斥反应,差异有显著性意义(P < 0.01)。发生急性体液排斥反应的患者中22例(88%)外周血清中检测到供者特异性抗体,271例无急性体液排斥反应的患者中仅1例检出供者特异性抗体,差异具有显著性意义(P < 0.01)。急性体液排斥反应受者中C4d阳性率为80%,未发生急性体液排斥反应的患者C4d阳性率仅为6.7%,差异具有显著性意义(P < 0.001)。肾移植后早期监测群体反应性抗体和供者特异性抗体水平,通过穿刺活检观察移植肾组织中的C4d沉积情况,可及时诊断急性体液排斥反应,有效改善移植物功能并提高移植物存活率。关键词：肾移植;供者特异性抗体;急性体液排斥反应;C4d;利妥昔单抗  doi:10.3969/j.issn.1673-8225.2012.18.005 中图分类号: R617  文献标识码: A   文章编号: 1673-8225(2012)18-03249-06     

移植肾活检：病理及组织学的早期诊断价值

背景：移植肾活检病理学组织学早期诊断意义重大,单中心回顾性研究临床诊断与治疗较少。 目的：通过对肾功能不全移植肾进行常规穿刺病理活检,根据病理诊断采取相应临床治疗方式,观察治疗效果,同时明确移植肾穿刺病理活检的安全性以及在临床诊治中的意义及其重要性。 方法：选取解放军第309医院器官移植中心202例肾移植患者为研究对象,其中80例为肾移植后移植肾功能延迟恢复,122例肌酐不明原因升高。在B超引导下应用活检穿刺针行移植肾穿刺活检,对活检组织标本予以相应染色和病理组织学观察,并进行相应的临床治疗。 结果与结论：穿刺组织中,除3例(1.5%)由于组织少难以诊断,其余病理诊断移植肾正常12例(5.9%),缺血再灌注损伤合并(或)急性肾小管坏死28例(13.9%),轻度钙调磷酸酶抑制剂类免疫抑制剂急性毒性损伤22例(10.9%),轻度钙调磷酸酶抑制剂类免疫抑制剂慢性毒性损伤12例(5.9%),超急性排斥反应1例(0.5%),疑为急性排斥反应29例(14.4%),急性T细胞性排斥反应34例(16.8%),急性抗体介导性排斥反应19例(9.4%),慢性T细胞介导排斥反应16例(7.9%),慢性T细胞介导排斥反应伴急性T细胞介导性排斥反应12例(5.9%),慢性抗体介导性排斥反应3例(1.5%),高血压因素4例(2.0%),间质纤维化和肾小管萎缩,未发现特定致病因素所致病变2例(1.0%),缺血性坏死2例(1.0%),移植后肾病复发３例(1.5%),C4d免疫组化染色阳性23例(11.4%),未发现患者及移植肾的不良反应。     

移植肾穿刺活组织检查：72例的病理及临床分析

背景：肾移植后慢性排斥反应及各种移植肾病变是移植肾失功能的常见原因,但对移植肾予以准确评估往往非常困难,活检仍是目前的主要手段。 目的：分析肾移植后出现合并症时移植肾穿刺活检的病理结果。 方法：对72例移植肾进行肾穿刺活组织检查,并进行病理诊断及分类,结合移植后情况进行分析。 结果与结论：72例中发生急性细胞介导性排斥反应35例,急性抗体介导性排斥反应12例,移植肾急性药物毒性损伤10例,慢性T细胞介导性排斥反应6例,慢性抗体介导性排斥反应2例,急性肾小管坏死4例,慢性移植肾肾病3例。移植肾组织活检的病理报告与穿刺前临床诊断的符合率在75%以上。移植肾穿刺活检未发生明显的不良反应。提示移植肾活检安全可靠,对肾移植后难以根据临床化验资料作出准确判断肾脏损害的并发症及治疗方案的选择有极为重要的指导意义。     

移植肾穿刺20例活组织病理检查的临床价值

背景：根据临床表现、无创性辅助检查及临床经验来判断肾移植后移植肾功能异常的原因常常会陷入困境,经皮肾穿刺活组织检查则可提供重要的循证学依据。 目的：探讨移植肾穿刺活组织检查的临床意义。 方法：回顾性分析20例移植肾穿刺活检病理资料及相应调整治疗后的临床结果资料。 结果与结论：20例患者病理诊断为急性排斥反应7例(35%),可疑性急性排斥反应2例(10%),可疑性急性排斥反应加免疫抑制剂中毒1例(5%),免疫抑制剂中毒3例(15%),慢性移植肾肾病3例(15%),未见明确异常3例(15%),肾小管坏死1例(5%)。相应调整治疗方案后,移植肾功能恢复正常9例(45%),移植肾功能好转7例(35%),肾功能无明显变化3例(15%),肾功能轻度恶化1例(5%)。结果可见肾穿刺活组织检查对肾移植后肾功能异常的病因诊断有重要的价值,有利于指导治疗方案的调整。     

Pathology of liver transplantation: an update

This article will concentrate on two main areas of liver allograft pathology where there have been significant advances during the past few years. The first is rejection, which continues to be a common cause of graft dysfunction in the early postoperative period and a rare cause of graft failure. Histological assessment remains essential to confirm the diagnosis of rejection. A recently developed, internationally accepted schema (the Banff schema) for grading acute rejection and staging chronic rejection will be described. With increasing numbers of people surviving long-term following transplantation, the issue of disease recurrence is becoming increasingly important. The second part of the paper deals with the histological diagnosis of disease recurrence and the assessment of other changes seen in biopsies obtained more than 12 months following liver transplantation.     

Expression of the interferon-inducible proteins MxA and IFI16 in liver allografts

Aims:  To test the hypothesis that the activation of the interferon (IFN) system pathways might link hepatitis C virus (HCV) recurrence in the liver allograft with acute cellular rejection.
Methods and results:  In this retrospective study, allograft biopsy specimens from 28 adult patients (14 HCV+ and 14 HCV−) who had undergone their first liver transplantation were analysed. Eleven biopsy specimens showed acute cellular rejection (Banff rejection activity index score ≥3). Specimens were immunostained for two IFN-inducible proteins, MxA and IFI16, and for CD45. The predominant MxA reactivity pattern was hepatocytic, whereas IFI16 was expressed in both the hepatocellular and inflammatory compartments. Moderate to strong MxA expression in hepatocytes was associated positively with rejection score ( P  < 0.01), donor's age ≤45 years ( P  < 0.05) and aspartate aminotransferase levels >40 U/l on the day of biopsy ( P  < 0.05), and inversely with infiltration of portal triads by IFI16+/CD45+ cells ( P  < 0.005) and time to progression beyond Ishak stage 2 of recurrent hepatitis C ( P  < 0.01). On multivariate analysis, MxA expression in hepatocytes was independently associated with allograft rejection and donor's age.
Conclusions:  Acute allograft rejection and recurrence of HCV infection in the liver allograft appear to intersect in the IFN system pathways.