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2023 11, No.5 Date of publication: 20 September 2023

Zhang Ying, Li Meihe, Zhang Weina, Kuang Peidan, Yan Xiaofei, Ding Xiaoming, Xue Wujun, Zheng Jin.

2023, (5): 404-411. DOI:10.3969/j.issn.2095-5332.2023.05.004

Objective To investigate non-HLA antibodies characteristics and its relationship with graft pathology after renal transplantation. Methods Non-HLA antibody data of 444 recipients after renal transplantation from 2016 to 2022 were retrospectively analyzed, the recipients were divided into rejection group (47 cases), nonrejection group (61 cases), and stable renal function group (336 cases) according to the pathological diagnosis of grafts. GraphPad Prism 9.0 was used to analyze the characteristics of non-HLA antibodies after kidney transplantation, the correlation between non-HLA antibodies and HLA antibodies, and the relationship between non-HLA antibodies and thepathological state of the renal allograft. Results Among the 444 recipients,310 cases (69.8%) were positive for nonHLA antibodies, which was positively correlated with HLA antibodies (r = 0.606,P < 0.001). The median of MFIvalue and the median multiple of the threshold value of non-HLA antibodies in recipients with positive HLA antibodies was higher than that in recipients with negative HLA antibodies post-transplant. There were differences in common nonHLA antibodies among rejection group, non-rejection group and renal function stable group. Non-HLA antibodies were positively correlated with chronic glomerulopathy (r = 0.186,P = 0.033) and interstitial fibrosis (r = 0.265,P = 0.002). Receiver operating characteristic curve (ROC) analysis showed that non-HLA antibodies were highly predictive of allograft arteritis (AUC = 0.771)and chronic nephropathy (AUC = 0.741), but were not good at predicting rejection (AUC =0.605). ConclusionThe positive rate of non-HLA antibodies was higher after renal transplantation. The common non-HLA antibodies in recipients with rejection, non-rejection and stable renal allograft function are different. Non-HLAantibodies are closely related to the chronic disease of graft kidney, and their predictive value for graft arteritis and chronic graft nephropathy is higher than that for rejection. 

Jin Meishan, Li Miao, Sun Li, Qu Limei.

2023, (5): 412-416. DOI:10.3969/j.issn.2095-5332.2023.05.005

 Objective The incidence,pathological changes and differential diagnosis of commoncomplications after liver transplantation have been studied,through a retrospective analysis of the pathological dataof 209 liver transplant biopsy tissues from a single center. Methods A total of 209 biopsies were performed in145 patients with liver transplantation from August 2013 to April 2023, at the Organ Transplantation Center of the First Hospital of Jilin University. The liver tissues were fixed with 4% neutral formaldehyde solution, embedded in paraffin and sectioned continuously, routinely HE staining, Masson, D-PAS, reticular fiber histochemical staining, CK7, CMV, C4dimmunohistochemical staining and EBER in situ hybridization were performed. Results Acute T cell-mediated rejection (TCMR) was the most common (36.84%) complication, followed by drug-induced liver injury(DILI)(23.44%) and biliary complications (14.35%), others include Hepatitis B and Hepatitis C virus infection or recurrence,ischemia-reperfusion injury, cytomegalovirus infection, chronic rejection, plasma cell-rich rejection, vascular complications, recurrent primary disease, primary graft dysfunction, and difficult-to-diagnose liver morphology. The diagnosis of acute T cell-mediated rejection was based on portal inflammation, bile duct inflammation and venous endothelial inflammation. In 58.44% cases of TCMR, the classic“Triad” of portal area was found. In DILI, there were swelling or ballooning degeneration of hepatocytes around central vein, steatosis with different degrees, cholestasis in hepatocytes and bile canaliculi. Biliary complication was characterized by cholestasis in hepatocytes and bile canaliculi, proliferation of small bile ducts along the interface of the portal tract,and interstitial edema.Conclusion The pathological diagnosis should be made after comprehensive analysisof the clinical manifestation, laboratory examination, imaging data and medication history. 

Zhai Lili, Wang Zhenglu, Yin Zhiqi, Zhang Fubo, Cao Kaiyue, Hu Zhandong, Wang Jingwen, Cai Wenjuan.

2023, (5): 417-423. DOI:10.3969/j.issn.2095-5332.2023.05.006

Objective To analyze the clinical and pathological characteristics ofpost-transplantlymphoproliferative disorder (PTLD) in children after liver transplantation, and to provide reference for diagnosis and treatment. Methods The clinical and pathological data of PTLD patients after liver transplantation were collected from May 2020 to May 2022 in the Pediatric Liver Transplantation Department of Tianjin First Central Hospital. The gender, age, surgical method, postoperative immunosuppression regimen, PTLD treatment regimen, prognosis, clinical manifestations,liver function, plasma EBV-DNA, and imaging examination results were included. Pathological classification and immunohistochemical staining results were analyzed according to WHO classification of lymphoid tissue tumors in 2016. The clinical, pathological and prognostic features of the patients were analyzed retrospectively. Results There were 8 patients with pathologically diagnosed PTLD after liver transplantation, including 4 males and 4 females, aged 1 ~ 4 years. All the 8 patients had biliary atresia as the primary disease and underwent living donor liver transplantation (LDLT). In this group,5 cases had lymph node enlargement,5 cases had digestive system symptoms (including abdominal pain,intestinal obstruction, ascites, and abdominal distension),4 cases had liver dysfunction,3 cases had fever, and 1 case had abnormal liver and kidney function. The mean plasma EBV-DNA was 46072copies/ml. The non-destructive, pleomorphic and monomorphic cases accounted for 12.5% (1/8),25% (2/8) and 62.5% (5/8), respectively. Burkitt lymphoma, diffuselarge B-cell lymphoma and mature T-cell lymphoma accounted for 60% (3/5),20% (1/5) and 20% (1/8) of monomorphic PTLD, respectively. After diagnosis, tacrolimus was tapered or discontinued. Six patients received chemotherapy and2 patients received hemodialysis. Two cases of local space occupying operation was performed. Of the 8 patients,7 caseshad remission and 1 died. Conclusion The early diagnosis of PTLD and the selection of reasonable treatment planaccording to pathological classification can improve the prognosis of patients. Children receiving chemotherapy should be alert to tumolysis syndrome and be given active and effective intervention in time. 

Ren Jiashu , Wang Zhenglu , Gao Wei , Yin Zhiqi , Cao Lei , Fan Shunli , Kong Dejun , Wang Hao , Li Jianghong , Yang Ruining , Zheng Hong , .

2023, (5): 424-429. DOI:10.3969/j.issn.2095-5332.2023.05.007

Objective To study the pathomorphological characteristics of extrahepatic portal vein wallthickening in children with biliary atresia, and to investigate the clinical significance and risk factors of the degree of extrahepatic portal vein wall thickening. Methods The clinicopathological data of 60 pediatric liver transplant recipients with biliary atresia from Children's Organ Transplantation Department of Tianjin First Central Hospital in June 2022 to December 2022 were analyzed. The pathomorphological changes of extrahepatic portal vein wall thickening in children with biliary atresia were observed. According to the median thickness of the total wall of extrahepatic portal vein, children with biliary atresia were divided into mild portal vein thickening group and severe portal vein thickeninggroup. The survival time of native liver after Kasai operation was compared between the two groups. Univariate and multivariate logistic regression were used to analyze the influencing factors of the degree of extrahepatic portal vein wallthickening. Results The wall of extrahepatic portal vein in children with biliary atresia was thickened to varyingdegrees, and the main pathological changes were interstitial edema under vascular endothelial cells, proliferation of fibers and fibroblasts, and a small amount of inflammatory cell infiltration. The intimal thickness of extrahepatic portal vein was 110(30 ~ 640)μm. Total wall thickness was 373(160~1320)μm. The ratio of portal vein intima thickness to total portal vein wall thickness was 0.341(0.105 ~ 0.636). Biliary atresia patients were furhter grouped, total wall hickness ≤ 373 μm was defined as portal vein mild thickening group, total wall thickness > 373 μm was defined as severe portal vein thickening group. The survival time of native liver in severe portal vein thickening group was significantly lowerthan that in mild portal vein thickening group (P < 0.05). Univariate analysis showed that Kasai operation history and cholangitis history were related factors affecting the degree of extrahepatic portal vein wall thickening in biliary atresia (P < 0.05). Multivariate analysis showed that the history of cholangitis was an independent risk factor for the degree ofextrahepatic portal vein wall thickening in biliary atresia (odds ratio = 4.000, 95% confidence interval as 1.272 ~ 12.578, P < 0.05).Conclusion Extrahepatic portal vein wall thickening in children with biliary atresia was mainly characterized by interstitial edema under vascular endothelial cells, proliferation of fibers and fibroblasts, and a small amount of inflammatory cell infiltration. The degree of extrahepatic portal vein wall thickening in biliary atresia may affect the survival time of native liver after Kasai operation. Prevention and treatment of cholangitis could help to reduce the degree of portal vein wall thickening. 

Wang Jingwen , Wang Zhenglu , Yin Zhiqi , Zhang mingfang , Cai Wenjuan .

2023, (5): 430-435. DOI:10.3969/j.issn.2095-5332.2023.05.008

 Objective To summarize the skin histopathological features of graft versus host disease (GVHD) after liver transplantation, and provide valuable reference for the pathological diagnosis and grading of GVHD. Methods Clinical data and skin biopsy pathological features of 10 patients with GVHD after liver transplantation from August 2018 to September 2022 in Transplant Center of Tianjin First Central Hospital were retrospectively analyzed. Enrollment criteria :complete clinical and pathological data of 10 patients. There was no history of specific medication prior to the appearance of the rash, and no previous history of skin disease. The age, sex, location and time of the first rash were summarized, and the histopathological manifestations of skin biopsy were statistically analyzed. The results included keratinocyte vacuolation, dyskeratosis, basal cell vacuolation, keratinocyte necrosis, basal layer fracture, epidermal total necrosis, epidermal dermal detachment, perivascular lymphocyte infiltration, epidermal atrophy, epithelial foot disappearance, pigment inence, and dermal collagen. HE staining was performed in all skin tissue biopsies and the images were reviewed by 2 pathologists. According to the existing GVHD skin pathological injury criteria, theclassification was performed, and the characteristics and rules of skin pathological changes in each group were statistically analyzed. Results There were 7 males and 3 females in this group,age ranging from 47 to 69 years old, with an average age of (59.5±6.8) years. The time of skin biopsy after transplantation ranged from 9 to 48 days (median time 31 days). All the 10 patients had skin rash as the first skin symptom, which spread from the abdomen to the limbs, head and neck. The incidence of basal cell vacuolation and lymphocyte infiltration around small vessels was 100%, the incidence of keratinocyte vacuolation and poor keratinization was 60%, and the positive rates of epidermal atrophy and keratinocyte necrosis were about 30%. Basal fissure and pigment incontinence accounted for about 20%. The positive rate of epithelial foot disappearance and dermal collagen was about 10%. No epidermal necrosis and epidermal dermal separation were found in this group, and the positive rate was 0%. The average number of lymphocytes infiltrated around a single vessel in the superficial dermis was 100% in both grade Ⅱ and grade Ⅲ GVHD skin lesions. Therefore, basal cell vacuolation and perivascular lymphocyte infiltration can be used as the important diagnostic basis for GVHD, while keratinocyte vacuolation and keratinized cells can be used as the main diagnostic basis for GVHD. The average number of infiltrated lymphocytes around a single blood vessel in the superficial dermis plays an important role in guiding the classification of GVHD injury. Conclusion The skin pathological features play important roles in the diagnosis and differential diagnosis of GVHD after liver transplantation. The number of infiltrated lymphocytes around a single blood vessel in the superficial dermis is an important histological reference for judging the grade and degree of GVHD injury. 

Wang Ye , Zhan Xiaohong , Li Yinan , Zhao Jing , Cai Wenjuan .

2023, (5): 436-440. DOI:10.3969/j.issn.2095-5332.2023.05.009

 Objective To analyzes the clinical and pathological characteristics of liver transplantation in2 children with pancreatoblastoma (PB) liver metastasis. Methods Theclinicopathological and immunophenotypic features of 2 children with multiple liver metastasis of PB were analyzed retrospectively. Two cases were detectedand followed up by immunohistochemical method, and the related literatures were reviewed to explore whether liver transplantation can be used as a new treatment for advanced PB in children. Results In the 2 cases of PB, the focus of liver was elevated AFP at the begining, pancreatic mass was found by imaging examination, pathological puncture showed liver metastasis of PB, and there was no obvious remission after chemotherapy. After pancreaticoduodenectomy and liver transplantation, routine pathological examination showed PB with multiple liver metastasis (stage Ⅳ). Immunophenotype :tumor cells simultaneously expressed AACT, CK, CK5/6, CD10,β-catenin and neuroendocrine markers (Syn, CgA, etc.). During the follow-up, the liver function was normal and there was no tumor recurrence and metastasis. Conclusion When liver metastasis occurs in children with advanced PB, the pathomorphological characteristics and immunohistochemical expression of liver metastasis are basically consistent with the primary focus of pancreas. For patients with multiple liver metastasis, better prognosis can be obtained after liver transplantation. 

Jiang Bodi, Meng Xianghong, Li Ruiping.

2023, (5): 441-446. DOI:10.3969/j.issn.2095-5332.2023.05.010

Objective The prediction of blood use during liver transplantation was analyzed bythe relevant indexes of thromboelastography (TEG) and conventional coagulation tests (CCTs) before liver transplantation. Methods Twenty-two patients undergoing liver transplantation from July 2016 to December 2021, the Hepatobiliary Department of the Eighth Medical Center of the People's Liberation Army General Hospital were monitored for TEG and CCTs before operation, and the data were statistically analyzed. Results Blood transfusion was mainlyused during and after liver transplantation. The ratio of suspended red blood cells to frozen plasma to platelets was 1 :2.31 :0.13. The number of red blood cells and plasma transfusion during liver transplantation had linear relationship with R,K, ANGLE, MA, PT, INR, APTT, HB and HCT. The number of platelets transfused had a linear relationship with K,ANGLE, PT, INR, APTT and HCT. Preoperative R value, MA, HB and HCT could predict whether a large amount ofblood was used during operation. TEG had certain correlation with CCTs. Compared with the group with MELD score >10 and the group with MELD score ≤ 10, the amount of red blood cells used during operation was significantly increased (P<0.05), the K value was significantly prolonged (P<0.05), the ANGLE angle was significantly decreased(P<0.05),and the MA value was significantly decreased (P < 0.01), with statistical differences. Conclusion The combination of TEG and CCTs to monitor the coagulation function of liver transplant patients before operation has certain guiding significance for the blood use during liver transplantation, especially for the prediction of large amount of blood use during liver transplantation. 

2023, (5): 447-450. DOI:10.3969/j.issn.2095-5332.2023.05.011

Objective To investigate the long-term efficacy of mycophenolic acid monotherapy in liver transplantation recipients. Methods The clinical data of 30 liver transplantation recipients in the Third Medical Center of PLA General Hospital from September 2002 to August 2020 were retrospectively analyzed. These patients were convertedfrom CNI regimen to MPA (CNI free) regimen due to toxicity, and their liver and kidney functions and adverse effectwerecompared before and after the conversion. The follow-up period was 2 years. Results The creatinine(Cr) levels at 1 and 2 years after conversion were (83.5±24.3)μmol/L and (74.2±15.9)μmol/L, respectively. The Cr level was significantly lower than that before conversion (P < 0.05). The estimated glomerular filtration rate (eGFR) was (77.7±9.1)ml/min and (86.1±6.5)ml/min, respectively. The eGFR level was significantly increased(P < 0.05). The alanine aminotransferase (ALT),aspartate aminotransferase(AST) and total bilirubin(TBil) levels had no significant changes before and after conversion(ALL P > 0.05). Conclusion The efficacy of mycophenolic acid monotherapy in long-term recipients of liver transplantation is worth affirming. 

Zhong Mingda, Lan Gongbin, Hu Shanbiao, Peng Longkai, Xie Yanbiao, Li Yanjin.

2023, (5): 451-456. DOI:10.3969/j.issn.2095-5332.2023.05.012

Objective There is an increased risk of tuberculosis infection after kidney transplantation, but tuberculous abscess after kidney transplantation is rarely reported. This article will discuss the clinical diagnosis andtreatment of tuberculous abscess after kidney transplantation and the causes of delayed diagnosis. Methods A total of 2173 patients who underwent deceased donor kidney transplantation in the Second Xiangya Hospital of Central South University from January 2015 to January 2023 were analyzed retrospectively. A total of 40 patients were diagnosed with tuberculosis post renal transplant, including 3 patients with tuberculous abscess. The clinical manifestations, diagnosis,treatment and prognosis of patients with tuberculous abscess were observed and analyzed. Results The mean time from kidney transplantation to the onset of the disease in 3 patients with tuberculous abscess was 15 months. The mean time from the onset to the start of antituberculosis therapy was 35.7 d and the mean time from onset to etiological diagnosis was 86.3 d. The anti-tuberculous and drainage treatment were effective. And serum creatinine had no significant change compared with that before treatment. Conclusion For patients with abscess after kidney transplantation, it is necessary to keep alert of the possibility of tuberculous infection. Especially for patients whose symptoms do not improve after conventional treatment,it is necessary to collect samples for etiological and molecular biological examination as soon as possible to confirm the diagnosis. For this kind of patients, the prognosis is favorable after regular anti-tuberculosis and drainage therapy at the same time. 

2023, (5): 457-463. DOI:10.3969/j.issn.2095-5332.2023.05.013

Objective To explore the risk factors related to delayed graft function (DGF) after kidney transplantation using machine learning algorithms and to establish a predictive model. Methods Clinical data of kidney transplant donors and recipients and pathological data of donor kidney biopsy from January 2018 to December 2020 at the Institute of Organ Transplantation of Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology were collected. The contribution of factors related to DGF were calculated through greedy algorithm,and logistic regression predict model were fitted using the reduced data set. Performance of the models is assessed by accuracy and area under the receiver operating characteristic curve (AUROC). Results The observed incidence of DGF was 21.9%. Risk factors that were highly correlated with DGF include donor body type, blood urea nitrogen, cold ischemia time, extent of artery lesions, as well as tubular atrophy score(ct) and interstitial fibrosisscores (ci). The prediction model was established using the above tested factors,the AUROC of the predict model was 0.71, and the prediction accuracy was 0.73. Conclusion Machine learning algorithms can be used to analyze the risk factors of DGF occurrence and establish predictive models. 

Han Xingxing, Ma Yige, Liang Zhao, Li Yue, Xia Shuang, Li Lei, Qi Shilin, Li Changhong, Zheng Xuetong, Song Zhen, Cheng Tao, Ma Shihui.

2023, (5): 464-469. DOI:10.3969/j.issn.2095-5332.2023.05.014

Objective To explore the establishment of standardized samples collection, storage,management and service system with complete facilities and information exchange for blood diseases, so as to achieve the standardized storage of a full range of hematological living cells and related blood components, and to provide resources for clinical research and transformation application. Methods The blood biobank was integrated with collection and processing, quality control, gene analysis and function identification, and has an independent storage area. It also has an integrated information management system connected with clinical diagnosis, treatment data and omics information. Characterized by the preservation of bone marrow living cells for blood diseases, standardized samplecollection, processing, storage and use procedures are established, and regular quality control testing is carried out. A comprehensive sharing mechanism and operational model was established. Results The blood biobank has stored a total of more than 400000 samples of hematological living cells and other related blood components, which has achieved full coverage of samples for all clinical diagnosis and treatment of disease types, and it has established more than 700 strains of disease derived iPSC. Six fresh and frozen samples, were randomly selected,and all of them were qualified, providing sample support for the high-quality scientific research output of the institute. Conclusion Standardized collection,preparation, storage and use of hematologic pathological living cells and related components can be achieved through the whole process control, an upgraded version of physical and virtual integration biobank that integrates biological samples,clinical diagnosis and treatment data, bioinformatics and other biomedical information and resources can be established.