器官移植

2020 Vol. 11, No. 3

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Editorial
Diagnosis and Treatment Specification
Expert Forum
Original Article
Guideline Interpretation
Review Article

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Editorial

The function of regulatory immunological cell in xenotransplantation immunity

Shi Bingyi, Chen Wen, Liu Zhijia

2020, 11(3): 321-325. doi: 10.3969/j.issn.1674-7445.2020.03.001

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Abstract:
Xenotransplantation is the most promising method to resolve the organ shortage problem in the future. In recent years, the advances in gene editing and immunological technique have driven the rapid development of xenotransplantation. However, there are still many insurmountable obstacles in the clinical application of xenotransplantation, among which the rejection is the most important cause of the xenotransplantation failure. Regulatory immunological cells are a group of immunological cells with the negative regulation function in the body, which can inhibit allotransplantation rejection and prolong the survival time of the graft. This paper summarized the research progress of regulatory immunological cells in the xenotransplantation application in recent years, providing reference for the prevention and treatment of xenotransplantation rejection.

Clinical progress of diagnostic and evaluation criteria for liver transplantation in patients with severe liver disease

Jia Yanan, Li Han, Li Xianliang, He Qiang

2020, 11(3): 326-332，368. doi: 10.3969/j.issn.1674-7445.2020.03.002

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Abstract:
Liver transplantation, although recognized as the only effective radical treatment for severe liver disease, might be accompanied by high surgical risks, high perioperative mortality and high postoperative complications. Considering the shortage of donor liver and related surgical risks, it is necessary to strictly control the indication of operation and the opportunity of transplantation. Therefore, accurate diagnosis and comprehensive evaluation of the condition of patients with severe liver disease to be treated by liver transplantation is an important part in determining the treatment plan. At present, there are many evaluation criteria for severe liver disease. In addition to the classic ChildTurcotte-Pugh (CTP) score and model for end-stage liver disease (MELD) score, many other evaluation criteria have also been developed. All transplant centers have their own choices and thus there is no uniform diagnostic criterion, with disputes among various criteria, which is exactly what this paper aims to summarize.

Diagnosis and Treatment Specification

Clinical technical specification for combined pancreas-kidney transplantation(2020 edition)

Branch of Organ Transplantation of Chinese Medical Association

2020, 11(3): 332-343. doi: 10.3969/j.issn.1674-7445.2020.03.003

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Abstract:
In order to further standardize the clinical techniques for combined pancreas-kidney transplantation, organ transplant specialists under the arrangement of Branch of Organ Transplantation of Chinese Medical Association have formulated this criterion from the aspects of diabetic kidney disease typing diagnosis, indications and contraindications of combined pancreas-kidney transplantation, surgery and surgical complications, immunosuppression programs, rejection, pathology, postoperative recurrent diabetes, follow-up of recipients, etc.

Expert Forum

Progress of immunosuppressant management, infection prevention and treatment after liver transplantation in severe liver disease

Li Han, Jia Yanan, He Qiang, Li Xianliang

2020, 11(3): 344-349. doi: 10.3969/j.issn.1674-7445.2020.03.004

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Abstract:
Liver transplantation is an effective treatment of severe liver disease. However, the pathophysiological changes of patients with severe liver disease are complicated, which significantly increase the difficulty of perioperative management of liver transplantation. Therefore, it is of great significance to strengthen postoperative management of the recipients with severe liver disease after liver transplantation. In this article, the pathophysiological characteristics of severe liver disease, the selection of immunosuppressant after liver transplantation, and the prevention and treatment of infection after liver transplantation in patients with severe liver disease were summarized.

Original Article

Evaluation of clinical prognosis of liver transplant recipients of hepatocellular carcinoma complicated with microvascular invasion

Liang Ziming, Ye Linsen, Tang Hui, Song Laien, Gu Shijie, Yi Shuhong

2020, 11(3): 350-355. doi: 10.3969/j.issn.1674-7445.2020.03.005

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Abstract:
Objective To investigate the clinical prognosis of the liver transplant recipients diagnosed with hepatocellular carcinoma (HCC) complicated with microvascular invasion (MVI). Methods Clinical data of 3 447 HCC recipients undergoing liver transplantation were extracted from Surveillance, Epidemiology, and End Results (SEER) database of American National Cancer Institute. According to the incidence of MVI, all recipients were divided into MVI (n=376) and non-MVI groups (n=3 071). The clinical prognosis of liver transplant recipients was statistically compared between two groups by analyzing the 1-, 3- and 5-year overall survival (OS) and liver cancer specific survival (LCSS). Relevant clinical data including age, gender, race, pathological staging, tumor size, lymph node metastasis, distant metastasis, tumor-node-metastasis (TNM) staging and MVI were recorded in two groups. The independent risk factors of clinical prognosis of HCC recipients undergoing liver transplantation were analyzed by multivariate Cox regression model. The nomogram for predicting the clinical prognosis of the recipients was delineated. The accuracy of the prediction model was evaluated by the consistency index. Results In the non-MVI group, the 1-, 3-, 5-year OS and LCSS were 93.5%, 82.1%, 75.3% and 98.3%, 93.8%, 90.7%, significantly higher than 88.8%, 72.1%, 68.4% and 95.3%, 83.1%, 80.4% in the MVI group (all P < 0.05). Multivariate regression analysis showed that pathological staging, tumor size, lymph node metastasis, distant metastasis, TNM staging and MVI were the independent risk factors of OS and LCSS in HCC recipients undergoing liver transplantation (all P < 0.05). The nomogram consistency index was calculated as 0.624 (0.602-0.648). Conclusions MVI is an independent risk factor of the clinical prognosis of HCC recipients undergoing liver transplantation, which is significantly correlated with poor prognosis of the recipients. The nomogram based on MVI can predict the clinical prognosis of these recipients.

Comparison between different perfusion methods for donor liver acquisition in rat liver transplantation model under direct vision of single operator

Li Lei, Li Shanbao, Wang Tao, Wo Qi, Cao Wanyue, Xu Junming

2020, 11(3): 356-361. doi: 10.3969/j.issn.1674-7445.2020.03.006

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Abstract:
Objective To establish a rat liver transplantation model under direct vision of single operator and to explore the effect of different perfusion methods on the quality of the donor liver. Methods On the basis of the "two-cuff method" established by Kamada, the operation details were improved to established the rat liver transplantation model. The recipient rats were divided into two groups according to different perfusion methods, group A (perfusion via abdominal aorta) and group B (perfusion via portal vein). The perfusion effect, operation time, operation success rate, postoperative liver function, liver graft pathological manifestations and survival were compared between the two groups. Results There were more residual red blood cells in sinus hepaticus in group B than in group A after perfusion. Both the donor liver perfusion time and donor operation time were longer in group A than those in group B, and the differences were statistically significant (both P < 0.01). The success rate of operation in group A and group B was 77% and 71%, respectively. At 3 d after liver transplantation in rats, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TB) of the rats in the two groups were significantly higher than normal. At 7, 30 d after operation, compared with group A, the levels of ALT, AST and TB in group B were significantly increased, and the differences were statistically significant (all P < 0.01-0.05). The liver pathological examination showed that the degree of inflammatory reaction in the liver and degree of destruction of liver tissue in group B were more severe than those in group A, but there was no significant difference in long-term survival rate between the two groups. Conclusions Although the perfusion time and donor operation time of rat liver transplantation model were slightly prolonged by means of abdominal aorta perfusion, the perfusion effect was better, which can reduce liver tissue damage after operation and restore liver function to normal levels more quickly.

Establishment and analysis of mouse model of acute antibody-mediated rejection in heart transplantation

Liao Tao, Yang Zhe, Zhang Yannan, Han Fei, Sun Qiquan

2020, 11(3): 362-368. doi: 10.3969/j.issn.1674-7445.2020.03.007

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Objective To establish a mouse model of acute antibody-mediated rejection (AMR) in heart transplantation and to analyze its characteristics. Methods Mouse models of heart transplantation and skin transplantation were established. According to different treatment methods, all animals were divided into the homologous control group, non-sensitized group, pre-sensitized group and pre-sensitized+ ciclosporin group (9 donors and 9 recipients in each group). The graft survival time, donor-specific antibody (DSA) level and pathological manifestations of each group were observed, and the characteristics of rejection were analyzed. Results In the homologous control group, the cardiac grafts of the mice survived for a long period of time during the 3-month observation period. The survival time of the cardiac grafts in the non-sensitized group, pre-sensitized group and pre-sensitized+ciclosporin group was (7.0±0.7) d, (2.6±0.5) d and (5.0±0.7) d, respectively. The differences among the groups were statistically significant (all P < 0.01). The DSA level in the pre-sensitized group was significantly elevated than the baseline level at 3 d after heart transplantation, and that in the pre-sensitized+ciclosporin group was remarkably up-regulated at 5 d after heart transplantation, the differences were statistically significant (P < 0.05, P < 0.01). The pathological manifestation of the non-sensitized group was the myocardial cell destruction, the formation of interstitial inflammation, mild C4d deposition and a large amount of CD3 cell infiltration. The pathological manifestations of the pre-sensitized group and the pre-sensitized+ciclosporin group showed myocardial cell destruction, capillary inflammation and a large amount of C4d deposition, whereas the amount of CD3 cell infiltration in the pre-sensitized group was more than that in the pre-sensitized+ciclosporin group. Conclusions The use of ciclosporin on the basis of heart transplantation and skin transplantation between different strains of mice can successfully establish a practical acute AMR model in mouse heart transplantation, which provides the basis for subsequent AMR pathogenesis and intervention research.

Comparison of the accuracy of RIFLE, AKIN and KDIGO criteria in predicting early death after liver transplantation

Liu Xun, Xue Mei, Wu Anshi

2020, 11(3): 369-373,390. doi: 10.3969/j.issn.1674-7445.2020.03.008

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Objective To compare the accuracy of three acute kidney injury (AKI) criteria of RIFLE, Acute Kidney Injury Network (AKIN) and Kidney Disease: Improving Global Outcomes (KDIGO) in predicting the early (30 d) postoperative death of liver transplant recipients. Methods Clinical data of 173 liver transplant recipients were retrospectively analyzed. The incidence of postoperative AKI was calculated according to the three criteria of RIFLE, AKIN and KDIGO. The all-cause fatality rate and cause of death at postoperative 30 d were analyzed. The risk factors of death within 30 d after operation were analyzed by binary Logistic regression. The prediction accuracy of three criteria for death within 30 d after operation was compared by the receiver operating characteristic (ROC) curve. Results According to the RIFLE, AKIN and KDIGO criteria, the incidences of postoperative AKI were 48.0%, 51.4% and 53.8%, respectively. Thirteen patients died within 30 d after operation and the fatality rate was 7.5%. RIFLE, AKIN and KDIGO stages were the independent risk factors for death within 30 d after operation (all P < 0.05). The area under the curve (AUC) of RIFLE, AKIN and KDIGO stages to predict death within 30 d after liver transplantation were 0.828, 0.766 and 0.844, respectively. There was a statistically significant difference between AKIN and KDIGO (P < 0.05). Conclusions KDIGO criterion is better for predicting early death after liver transplantation. However, as a tool, the comparative selection among these three criteria still needs the evidence support from a large multicenter sample.

Effect of low postoperative platelet count on early fatality rate of adult liver transplantation without platelet transfusion during operation

Wang Sainan, Wu Zhitao, Wu Yan, Wu Anshi

2020, 11(3): 374-378. doi: 10.3969/j.issn.1674-7445.2020.03.009

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Objective To investigate the effect of low platelet (PLT) count on the early fatality rate of liver transplant recipients without intraoperative PLT transfusion. Methods Clinical data of 180 recipients undergoing orthotopic liver transplantation were retrospectively analyzed. The critical value of PLT count on postoperative 7 d to predict the early postoperative fatality rate was evaluated by the receiver operating characteristic(ROC) curve. All recipients were divided into the low PLT count group and control group according to the critical value. Relevant clinical data including perioperative PLT count, preoperative general conditions and intraoperative conditions of the recipients were included. The independent risk factors of the early fatality rate of liver transplant recipients were analyzed by Logistic regression analysis. The early prognosis of the recipients between two groups was observed and compared by the postoperative length of intensive care unit (ICU) stay, postoperative length of hospital stay, early allograft dysfunction and fatality rate on postoperative 30 d. Results The PLT count < 32×10⁹/L on 7 d after liver transplantation was an independent risk factor of the fatality rate on postoperative 30 d (P < 0.05). The postoperative length of ICU stay of the recipients in the low PLT count group was 9 (5, 14) d, significantly longer than 5 (3, 6) d in the control group (P < 0.05). In the low PLT count group, the early allograft dysfunction rate was 55.0%, significantly higher than 20.6% in the control group (P < 0.05). In the low PLT count group, the fatality rate on postoperative 30 d was 40.0%, significantly higher than 2.5% in the control group (P < 0.05). The length of hospital stay did not significantly differ between two groups (P > 0.05). Conclusions The PLT count < 32×10⁹/L on postoperative 7 d is an independent risk factor for the fatality rate on postoperative 30 d of liver transplant recipients. It can prompt the early allograft dysfunction and contribute to predict the early clinical prognosis of liver transplant recipients.

The efficiency study on different scoring models in predicting delayed graft function after renal transplantation

Qiao Yuxi, Ding Chenguang, Tian Puxun, Ding Xiaoming, Pan Xiaoming, Yan Hang, Xiang Heli, Feng Xinshun, Hou Jun, Tian Xiaohui, Li Yang, Zheng Jin, Xue Wujun

2020, 11(3): 379-383. doi: 10.3969/j.issn.1674-7445.2020.03.010

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Objective To analyze the prediction efficiency of scoring models at home and abroad on delayed graft function (DGF) after renal transplantation in China. Methods The clinical data of 112 donors and 220 recipients undergoing renal transplantation were prospectively analyzed. The DGF predicted by KDRI model, Jeldres model, and model of our center was compared with actual DGF incidence of renal transplant recipients. The prediction efficiency of each model was analyzed. The predictive accuracy was compared by the area under curve (AUC) of receiver operating characteristic (ROC) curve. Results The DGF incidence of 220 renal transplant recipients was 14.1% (31/220). DGF prediction using KDRI model showed that 41 cases were high risk donors, the AUC was 0.57, the sensitivity was 0.37, the specificity was 0.66, and the positive predictive value was 22%. DGF prediction using Jedres model showed that 22 cases were high risk recipients, the AUC was 0.56, the sensitivity was 0.13, the specificity was 0.92 and the positive predictive value was 20%. DGF prediction using the model of our center showed that 25 cases were high risk donors, the AUC was 0.80, the sensitivity was 0.53, the specificity was 0.84, the positive predictive value was 40%. Conclusions Compared with the KDRI and Jedres models, the prediction model of our center has higher AUC and sensitivity with a better prediction efficiency on DGF. Therefore, it is a suitable evaluation system of donors from donation after citizen's death in Chinese.

Systematic evaluation on PD-1 monoclonal antibody in the treatment of malignant tumor after solid organ transplantation

Bin Yangyang, Li Jiequn, Li Qiang, Zhou Zhengjun, Zhou Yi, Chen Guangshun, Qi Haizhi, Si Zhongzhou

2020, 11(3): 384-390. doi: 10.3969/j.issn.1674-7445.2020.03.011

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Objective To investigate the efficacy and safety of programmed cell death protein-1 (PD-1) monoclonal antibody on the treatment of malignant tumor after solid organ transplantation (SOT). Methods The relevant literatures in 7 databases were searched. The data on 54 cases of recipients with malignant tumors treated with PD-1 monoclonal antibody after SOT were collected, and the clinical effects and rejection of SOT recipients treated with PD-1 monoclonal antibody were analyzed. Results Total 32 acceptable articles including 54 SOT recipients were incorporated, including 43 males and 11 females aged 14-79 years old. There are 29 renal transplant recipients, 19 liver transplant recipients and 6 heart transplant recipients. The types of PD-1 monoclonal antibody agent used by SOT recipients included pembrolizumab for 28 patients and nivolumab for 26 patients. The overall remission rate, disease progression rate and fatality rate of PD-1 monoclonal antibody for postoperative malignant tumors of SOT recipients were 32% (17/54), 44% (24/54) and 36% (19/54), respectively. After treatment with PD-1 monoclonal antibody for postoperative malignant tumors of SOT recipients, the incidence of rejection was 39% (21/54), indicating no significant correlation between rejection and type of PD-1 monoclonal antibody (P > 0.05). Conclusions PD-1 monoclonal antibody can effectively treat postoperative malignant tumors of SOT recipients, and may induce rejection during the treatment. But rejection is not the most common cause for death of recipients.

Lung transplantation for cystic fibrosis: a case report and literature review

Chen Ao, Lian Qiaoyan, Xu Xin, Wei Bing, Liu Mengyang, Peng Guilin, Zhang Jianheng, He Jianxing, Ju Chunrong

2020, 11(3): 391-394,423. doi: 10.3969/j.issn.1674-7445.2020.03.012

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Objective To investigate the clinical efficacy and prognosis of lung transplantation in the treatment of cystic fibrosis (CF). Methods Clinical data of one patient with end-stage CF undergoing allogeneic bilateral lung transplantation were retrospectively analyzed. Clinical characteristics, diagnostic methods and treatment strategies of the CF recipient were summarized. Results The recipient had suffered from relevant symptoms since childhood including repeated cough and purulent sputum for 30 years, complicated with recurrent pulmonary infection combined with acute exacerbation, chronic sinusitis and extremely severe malnutrition. Prior to lung transplantation, the patient had to depend upon the invasive ventilator due to respiratory muscle weakness, and admitted to intensive care unit (ICU) for a long time. Imaging examination revealed multiple cystic columnar bronchiectasis accompanied with infection in bilateral lungs. The diagnosis of CF was further confirmed by sweat test and gene detection. The recipient underwent bilateral lung transplantation on August 17, 2017 and received rehabilitation treatment. The lung function was gradually restored to normal. The recipient had obtained the same quality of life to the healthy counterparts since the date of manuscript submission (over 2 years). Conclusions Lung transplantation is an efficacious treatment for end-stage CF, which can not only save patients' lives, but also significantly improve the quality of life of patients.

Guideline Interpretation

Interpretation of Guide to the Quality and Safety of Organs for Transplantation(6th edition): identification and referral of potential donors

Dong Jianhui, Liu Xuyang, Wang Hongliang, Liao Jixiang, Yang Dongge, Su Qingdong, Lu Haisheng, Lan Liugen, Li Haibin, Wen Ning, Qin Ke, Sun Xuyong

2020, 11(3): 395-399. doi: 10.3969/j.issn.1674-7445.2020.03.013

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Organ shortage is one of the important factors restricting the development of human organ transplantation. The identification and referral of potential donors determine the total scale of organ donation. Whether potential donors can be identified and referred is the most important reason for the difference of organ donation rates in different regions. This paper interprets the chapter of the identification and referral of potential donors in the Guide to the Quality and Safety of Organs for Transplantation (6th edition) issued by European Union in order to provide reference for the staff of organ procurement organization and related medical personnel in China and improve the organ donation rate in China.

Interpretation of Guide to the Quality and Safety of Organs for Transplantation(6th edition): risk of malignant tumor transmission

Lin Jun, Li Shixin, Yang Yang

2020, 11(3): 400-404. doi: 10.3969/j.issn.1674-7445.2020.03.014

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As China enters the era of organ donation after the citizen's death, the organ donation cases with potential malignant tumor history increase gradually. Guide to the Quality and Safety of Organs for Transplantation (6th Edition) by European Committee was translated into Chinese in 2019. This article interprets Chapter 9 of the guideline "Risk of Malignant Tumor Transmission" to assist organ donation coordinator and transplant team in screening donors at risk of malignant tumor transmission in our country and to reduce the risk of donor-derived tumor transmission.

Review Article

Research progress on carbapenem-resistant Klebsiella pneumoniae infection in organ transplantation

Liu Weiwang, Wang Xiao, Li Chuanchang

2020, 11(3): 405-412. doi: 10.3969/j.issn.1674-7445.2020.03.015

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Klebsiella pneumoniae (KP) is a common conditional pathogen, and also one of the common pathogens causing infection in immunocompromised patients, with its infection rate increasing year by year. Carbapenem antibiotics are effective drugs to control KP infection. But with the widespread use of carbapenem antibiotics, carbapenemresistant Klebsiella pneumoniae (CRKP) appears and increases year by year. Organ transplant recipients are at high risk of CRKP infection due to the suppressed immune system. Once drug-resistant bacteria infection occurs, it is often difficult to control and the survival rate of transplant organs is reduced, which brings great challenges to clinical treatment. In this article, the current status and treatment progress of CRKP infection in organ transplantation are summarized.

Research progress on liver transplantation for alcoholic liver disease

Duan Fangfang, Cheng Jun, Yang Song

2020, 11(3): 413-418. doi: 10.3969/j.issn.1674-7445.2020.03.016

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Liver transplantation is a major treatment for patients with alcoholic liver disease (ALD)-related end-stage cirrhosis, liver failure, hepatocellular carcinoma (HCC) and severe alcoholic hepatitis. In this article, the latest research progress on liver transplantation in ALD patients was summarized from the aspects of surgical indications, survival status, alcohol-drinking management and systemic disease management of the recipients, aiming to provide reference for better clinical management of ALD recipients undergoing liver transplantation.

Research status of liver transplantation in the treatment of non-alcoholic fatty liver disease

Yang Zhou, Fu Binsheng

2020, 11(3): 419-423. doi: 10.3969/j.issn.1674-7445.2020.03.017

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Liver transplantation is the most effective means to treat the related end-stage liver disease caused by non-alcoholic fatty liver disease (NAFLD). But the recurrence rate of NAFLD after liver transplantation is very high due to the affection of obesity, metabolic syndrome and other adverse factors. In recent years, liver transplantation for NAFLD related end-stage liver disease has made some progress both in China and abroad. This article reviews the research progress of NAFLD and liver transplantation for NAFLD.

Research progress of nervous system and neurocognition-related complications after liver transplantation

Miao Xiaolei, Wu Yan, Wu Anshi

2020, 11(3): 424-430. doi: 10.3969/j.issn.1674-7445.2020.03.018

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The postoperative nervous system and neurocognition-related complications have become an important issue of research focus with the gradual increase of the survival rate after liver transplantation. Compared to other solid organ transplantation, the incidence of nervous system complications after liver transplantation is higher and closely related to death. This paper mainly overviewed the nervous system complications, neurocognition-related complications after liver transplantation and the risk factors inducing these complications. It also discussed how to evaluate, monitor, and prevent these complications in order to provide reference for future studies.