器官移植

2020 Vol. 11, No. 4

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Editorial
Transplantation Forefront
Original Article
Guideline Interpretation
Donation Window
Special Column of COVID-19 Pneumonia
Review Article

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Editorial

Multidisciplinary cooperation of achieving the optimal clinical efficacy of pediatric liver transplantation

Yi Shuhong, Yang Yang, Chen Guihua

2020, 11(4): 431-434. doi: 10.3969/j.issn.1674-7445.2020.04.001

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Abstract:
With the maturity of the technique of adult liver transplantation, pediatric liver transplantation has been gradually emerging in major liver transplantation centers throughout China. Pediatric liver transplantation differs from adult liver transplantation in terms of recipient selection, technical details, perioperative management, postoperative treatment and follow-up, etc. Multidisciplinary cooperation is required to continuously improve the clinical efficacy of pediatric liver transplantation. In this article, we reviewed the significance of multidisciplinary cooperation in achieving the optimal clinical efficacy of pediatric liver transplantation, in respect to the recipient selection and extrahepatic organ function evaluation, mastering the technical key points of different types, improving the quality of postoperative follow-up, and formulating clinical diagnosis and treatment strategies, etc.

Transplantation Forefront

Research progress on myeloid-derived suppressor cell and transplantation immune tolerance

Yuan Shun, Wang Zhiwei

2020, 11(4): 435-442. doi: 10.3969/j.issn.1674-7445.2020.04.002

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Abstract:
Myeloid-derived suppressor cell (MDSC) is a type of heterogeneous cell derived from bone marrow, which was first found in tumor. MDSC can inhibit the function of T cell with immunosuppressive effect. In recent years, more and more studies have shown that in the field of organ transplantation, MDSC can also regulate the host's immune function, induce specific immune tolerance, and play a protective role in transplant organs, which is expected to become a new target in clinical treatment of transplant rejection. The biological characteristics of MDSC and the mechanism of immune tolerance induced by MDSC were reviewed in this paper.

Original Article

The application value of Multi-Latex polygranular technique joint detection of urinary microproteins in noninvasive diagnosis after renal transplantation

Li Shengbing, Chen Wen, Li Xiubin, Ma Xihui, Sun Yujie, Bi Lili, He Xiuyun, Han Yong, Xiao Li, Shi Bingyi

2020, 11(4): 443-448. doi: 10.3969/j.issn.1674-7445.2020.04.003

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Objective To investigate the application value of Multi-Latex polygranular technique joint detection of kidney injury-related urinary microproteins in noninvasive diagnosis after renal transplantation. Methods Clinical data of 72 recipients undergoing renal transplantation were retrospectively analyzed. According to the level of serum creatinine (Scr), the recipients were divided into normal renal function group (group A, n=14), mild kidney injury (group B, n=37), and severe kidney injury group (group C, n=21). 20 healthy volunteers were selected as the healthy control group (HC group). The contents of urinary retinol binding protein (RBP), microalbumin (mAlb), IgG, transferrin (TRF), α₁-microglobulin (MG), and β₂-MG of subjects in each group were detected using the Multi-Latex polygranular technique. The correlation between urinary microproteins and Scr, blood urea nitrogen (BUN) was analyzed. The differences of urinary microproteins in each group were compared. And the diagnostic value of single and joint detection of urinary microproteins was evaluated. Results Six kinds of urinary microproteins in HC group and group A were significantly lower than those in group B and group C, and six kinds of urinary microproteins in group B were significantly lower than those in group C (all P < 0.01). Six kinds of urinary microproteins in renal transplant recipients were positively correlated with BUN. RBP, mAlb, α₁-MG, and β₂-MG were positively correlated with Scr. The correlations were statistically significant (P < 0.001-0.05). The diagnostic value of joint detection of urinary microproteins is better than the detection of single index, among which TRF+mAlb+RBP+α₁-MG quadruple detection had the highest diagnostic value. Conclusions Six kinds of urinary microproteins can be used as specific indicators to reflect graft renal function. The polygranular technique can simultaneously detect its contents and achieve noninvasive diagnosis. The diagnosis based on TRF+mAlb+RBP+α₁-MG quadruple detection is expected to further improve the noninvasive diagnosis system after renal transplantation.

De novo malignant tumor after renal transplantation: single-center trial

Su Daming, Deng Wenfeng, Liu Rumin, Li Jiangtao, Fu Fangxiang, Ni Haiqiang, Hu Yangcheng, Yu Lixin, Xu Jian, Miao Yun

2020, 11(4): 449-454. doi: 10.3969/j.issn.1674-7445.2020.04.004

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Objective To analyze the incidence and risk factors of de novo malignant tumors in renal transplant recipients. Methods Clinical data of 1 549 renal transplant recipients were retrospectively analyzed, including the basic status, pathological type and incidence rate of patients with de novo malignant tumors after renal transplantation. The survival situation of these patiensts was assessed. And the risk factors of de novo malignant tumors after renal transplantation were identified. Results The incidence rate of de novo malignant tumors in renal transplant recipients was 3.03%(47/1 549). The 47 recipients were (48±12) years old when undergoing renal transplantation, and they were (55±12) years old when diagnosed malignant tumors. The time interval between transplantation and diagnosis was 66 (36, 100) months. Among the de novo malignant tumors, colorectal cancer was the most common, with a cumulative incidence rate (CIR) of 0.58%. The survival time of 47 recipients with de novo malignant tumors after renal transplantation was 59 (2, 135) months, and the 5-year survival rate was 50%. The recipients with the age > 45 years old when undergoing renal transplantation was a risk factor for de novo malignant tumors after renal transplantation (P < 0.05). Conclusions The incidence rate of de novo malignant tumors is relatively high in renal transplant recipients. The recipients with the age > 45 years old when undergoing renal transplantation is a risk factor for de novo malignant tumors.

Individualized medication of tacrolimus after liver transplantation guided by CYP3A5*1 gene polymorphisms: a prospective controlled study

He Li, Li Guangming, Lin Dongdong, Liu Jinning, Wang Xin, Wang Lu

2020, 11(4): 455-460. doi: 10.3969/j.issn.1674-7445.2020.04.005

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Objective To evaluate the safety and efficacy based on cytochrome P450(CYP)3A5*1 gene polymorphisms in guiding the individualized medication of tacrolimus (FK506) after liver transplantation. Methods Clinical data of 100 consecutively enrolled recipients who underwent liver transplantation for the first time were analyzed and randomly divided into experimental group and control group, with 50 cases in each group. The donors and recipients in the experimental group received preoperative CYP3A5 gene detection, and determined the FK506 medication regimen according to the CYP3A5*1 genotype. The compliance rate of FK506 target blood concentration, the recovery rate of liver function in the two groups of recipients at 7, 14, 28 d and 3, 6, 9, 12 months postoperatively, as well as the number of FK506 dosage adjustment during the follow-up were observed. The 1-year graft survival rate and the incidence of complications were recorded in both groups of recipients, such as acute rejection, infection, acute kidney injury, gastrointestinal symptoms, de novo hypertension, de novo diabetes, colds and rash, etc. Results The differences of the compliance rate of FK506 target blood concentration between the two groups of recipients at 7, 14 d after operation were statistically significant (both P < 0.05). There was no statistically significant difference between the two groups in the compliance rate of FK506 target blood concentration at 28 d and 3, 6, 9, 12 months and the recovery rate of liver function at the 7 observation time points after operation (all P > 0.05). The difference between the two groups of recipients in number of FK506 dose adjustment during follow-up was statistically significant (P=0.021). There were no statistically significant differences in 1-year graft survival rate and incidence of complications between the two groups of recipients after operation and during follow-up (all P > 0.05). Conclusions It is safe to guide individualized medication of FK506 after liver transplantation according to CYP3A5*1 gene polymorphism. It can increase the compliance rate of FK506 target blood concentration of recipients in the early postoperative stage, and can effectively reduce the number of dose adjustment duringfollow-up.

Rare complication after pediatric living donor liver transplantation: right diaphragmatic hernia

Qu Wei, Zhu Zhijun, Wei Lin, Sun Liying, Zeng Zhigui, Liu Ying, Wang Jun, Tan Yule, Zhang Liang, He Enhui

2020, 11(4): 461-465. doi: 10.3969/j.issn.1674-7445.2020.04.006

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Objective To analyze the clinical characteristics, pathogenic causes and therapeutic experience of right diaphragmatic hernia after pediatric living donor liver transplantation. Methods Clinical data of 3 recipients with right diaphragmatic hernia after pediatric living donor liver transplantation were retrospectively analyzed. The clinical characteristics, diagnosis and treatment process and therapeutic experience were analyzed and summarized. Results The primary diseases of 3 children with diaphragmatic hernia after living donor liver transplantation were biliary atresia. The diaphragmatic hernia occurred at 4-6 months after liver transplantation. The contents of diaphragmatic hernia included the intraperitoneal and interperitoneal tissues and organs. Diaphragmatic defects were all located in the posterior medial area of the right diaphragm. The primary stage intermittently suturing repair was performed during intraoperative period. No diaphragmatic hernia recurred during long-term follow-up. Conclusions The clinical manifestations of right diaphragmatic hernia after pediatric living donor liver transplantation are diverse. The risk factors include malnutrition, low body weight, surgical trauma, chemical erosion caused by bile leakage, focal infection and pleural-peritoneal pressure gradient, etc. Surgical intervention is the preferred treatment strategy for diaphragmatic hernia after liver transplantation.

Clinical efficacy analysis of pediatric blood type incompatible living donor liver transplantation

Sun Chao, Meng Xingchu, Dong Chong, Wang Kai, Zheng Weiping, Qin Hong, Han Chao, Yang Yang, Zhang Fubo, Cao Shunqi, Xu Min, Gao Wei

2020, 11(4): 466-470. doi: 10.3969/j.issn.1674-7445.2020.04.007

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Objective To explore the clinical efficacy of pediatric blood type incompatible living donor liver transplantation. Methods The clinical data from 242 cases of pediatric living donor liver transplantation recipients were retrospectively analyzed. Recipients were assigned to group A (ABO-identical group, n=165), group B (ABO-compatible group, n=42) and group C (ABO-incompatible group, n=35) according to the blood type compatibility between the recipients and the donors. The occurrence of postoperative complications and development of postoperative donor specific antibody (DSA) among the 3 groups were observed and compared. And the blood type distribution of donors and recipients and development of erythrocyte antibodies in group C were analyzed. The survival situation of recipients after liver transplantation was compared among the 3 groups. Results There was no significant difference in the incidence of complications among the 3 groups(all P > 0.05). DSA was dominated by human leukocyte antigen (HLA) Ⅱ antibodies after liver transplantation, mostly anti-HLA-DR and anti-HLA-DQ. The postoperative erythrocyte antibodies for liver transplant recipients in group C were dominated by IgM, with titers ≤1:2 for all. The differences in postoperative survival rates were not statistically significant among 3 groups(all P > 0.05). Conclusions Pediatric blood type incompatible living donor liver transplantation is a safe and effective treatment, which can effectively expand the source of liver transplant donors and save the children's lives.

Gu Guangxiang, Zong Zhipeng, Zhou Tao, Xia Qiang

2020, 11(4): 471-476. doi: 10.3969/j.issn.1674-7445.2020.04.008

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Objective To summarize the therapeutic effects of living related donor liver transplantation for Crigler-Najjar syndrome type Ⅰ (CNS type Ⅰ). Methods A 3-month-old male infant had appeared a progressive xanthochromia of the skin and sclera 4 d after birth without obvious cause. Other causative factors were eliminated after relevant tests were completed, and identified as CNS type Ⅰ by genetic testing. Living related donor liver transplantation was performed with his mother as the donor. An immunosuppression regimen was routinely applied postoperatively and tacrolimus doses were adjusted according to biochemical indicators and cytochrome P450 (CYP) 3A5 genotype of the recipient. Results The liver enzymes of the recipient returned to normal at 7 d postoperatively, and bilirubin decreased daily and fell to the normal range at 22 d postoperatively. Followed up to the submission date, the recipient's xanthochromia of skin and scleral faded with normal bilirubin and stable liver enzymes. The condition of the recipient was generally good with high quality of life. Conclusions Living donor liver transplantation can treat unconjugated hyperbilirubinemia and other diseases caused by CNS type Ⅰ, which greatly improve the quality of life of patients.

Risk factor analysis and predictors assessment for postoperative delirium in liver transplantation

Chen Junguo, Wang Hao, Xie Bin, He Zhijun, Li Ting

2020, 11(4): 477-481. doi: 10.3969/j.issn.1674-7445.2020.04.009

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Objective To analyze the risk factors and predictors related to postoperative delirium(POD) in liver transplantation. Methods The clinical data of 232 liver transplant recipients were retrospectively analyzed. Recipients were assigned to POD group (n=60) and non-POD (n=172) group according to the presence of POD. The intra- and post-operative conditions were compared between the two groups of liver transplant recipients. The risk factors for occurrence of POD in liver transplant recipients were analyzed using multifactorial analysis. And the value of predicting the occurrence of POD in liver transplant recipients according to the risk factors were assessed. Results The incidence of POD in liver transplant recipients was 25.9%. The operation time and anhepatic phase in the POD group were longer than those in the non-POD group. Intraoperative infusion of erythrocyte, infusion of cryoprecipitate, and lactic acid level were higher than those in the non-POD group (all P < 0.05). The levels of postoperative alanine aminotransferase (ALT), aspartate aminotransferase (AST), prothrombin time international normalized ratio (PT-INR), and plasma fibrinogen in the POD group were significantly higher than those in the non-POD group (all P < 0.05). Preoperative hepatic encephalopathy, elevated blood ammonia, high score of model for end-stage liver disease (MELD), elevated postoperative AST level and long intraoperative anhepatic phase were the independent risk factors for POD in liver transplant recipients (all P < 0.05). Preoperative elevated blood ammonia and high MELD score showed profound value in predicting the occurrence of POD in liver transplant recipients, with best cut-off values of 42.6 μmol/L and 18 points, sensitivity of 0.650 and 0.767 as well as specificity of 0.826 and 0.727, respectively. Conclusions The incidence of POD is high in liver transplant recipients. Preoperative hepatic encephalopathy, elevated blood ammonia, high MELD score, elevated postoperative AST level, and long intraoperative anhepatic phase are independent risk factors for liver transplant POD. Preoperative elevated blood ammonia and high MELD score are predictors of POD in transplant recipients.

esearch on clinical efficacy of liver transplantation for severe liver disease

Kou Jiantao, Liu Zhe, Zhu Jiqiao, Ma Jun, Xu Wenli, Li Han, Jia Yanan, Li Xianliang, He Qiang

2020, 11(4): 482-486. doi: 10.3969/j.issn.1674-7445.2020.04.010

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Objective To explore the clinical efficacy of liver transplantation for severe liver disease. Methods The clinical data of 51 patients who underwent liver transplantation for severe liver disease were retrospectively analyzed. The general intraoperative conditions were observed, including operation duration, warm ischemia time, cold ischemia time, anhepatic phase, bleeding volume, blood transfusion volume, plasma transfusion volume and so on. The changes in indexes such as total bilirubin (TB), prothrombin time activity (PTA), and prothrombin time international normalized ratio (PT-INR) were observed before operation and at 3 d, 1 week and 2 weeks after operation. The postoperative survival and occurrence of complications were analyzed. The indexes that might affect the prognosis of patients with severe liver disease were analyzed by Cox regression analysis. Results For the 51 patients, operation duration, warm ischemia time and cold ischemia time was 8 (7, 9) h, 3 (2, 3) min and 6 (5, 8) h respectively, intraoperative anhepatic phase was 80 (70, 100) min, intraoperative bleeding volume was 1 000 (550, 1 500) mL, and intraoperative blood transfusion volume was 1 200 (200, 1 600) mL. Postoperative TB, PTA, PT-INR and other indexes improved significantly compared to those preoperatively. Among the 51 patients, 10 cases died, with the death causes of multiple organ failure and severe infection(7 cases), renal insufficiency (2 cases), and cardiovascular complications (1 case). Survival rates at 1 month and 1 year post-transplantation for patients with severe liver disease were 82% and 80%, respectively. Cox regression analysis suggested that abnormal preoperative PTA and PT-INR were the risk factors for post-transplantation death in patients with severe liver disease. Conclusions Liver transplantation significantly improves the survival rate for patients with severe liver disease, perioperative infection prevention and treatment as well as multiple organ function management play key roles in improving post-transplantation survival rate in patients with severe liver disease.

Guideline Interpretation

Interpretation of Guide to the Quality and Safety of Organs for Transplantation (6th edition): evaluation and selection criteria for donors and organs

Xie Liangbo, Xia Qiuxiang, Zeng Xianpeng, Peng Jingtao, Li Heng, Xiao Hanyu, Chen Jing, Liu Jing, Wang Zhendi

2020, 11(4): 487-491. doi: 10.3969/j.issn.1674-7445.2020.04.011

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Organ transplantation is the most effective method to treat end-stage organ failure. As the increase of transmission risk of donor-derived diseases, the quality, safety and selection criteria of transplanted organs become more and more important. Chapter 7 of the European Union's Guide to the Quality and Safety of Organs for Transplantation (6th Edition) proposed basic requirements in terms of donor and organ quality assessment, selection criteria and procedures, which were worthy of study and practice in clinical practice.

Donation Window

The choice of communication specialist for family member of organ donation and corresponding strategy for work difficulty

Liao Yuan, Wang Xuewen, Guo Yong, Liu Yajie, Jiang Wenshi

2020, 11(4): 492-496. doi: 10.3969/j.issn.1674-7445.2020.04.012

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Communication with the family members of donors is an integral part of the organ donation and transplantation, and the core of it lies in building trust through interpersonal communication. Every word and deed from the communicator will directly affect the overall impression of family members of potential donors towards organ donation. Regardless of whether or not granted the donation ultimately, family members may share their personal experiences and feelings with friends and relatives around them, which develops a secondary dissemination. Therefore, "the choice of best candidate for communication with family members of organ donation" has been an issue that organ donation practitioners have been working on in clinical practice. Taking into consideration of the experiences from different countries or regions, various advices and practices on this issue have been proposed due to differences in social systems, cultural background, organizational structure, clinical practice, etc. In this paper, we had a discussion on this topic, summarize the difficulties currently encountered in communication with family members and propose corresponding strategies.

Special Column of COVID-19 Pneumonia

Operation cooperation and management of bilateral lung transplantation for the first case with novel coronavirus pneumonia in the world

Xu Haiying, Qin Jianan, Chen Jingyu, Sheng Ling, Dong Zhiqiang, Zhou Li, Dai Yu

2020, 11(4): 497-501. doi: 10.3969/j.issn.1674-7445.2020.04.013

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This paper summarized the operation cooperation and management of the first case of bilateral lung transplantation assisted with double extracorporeal membrane oxygenation (ECMO) for the recipient with novel coronavirus pneumonia (COVID-19) in the world. The bilateral lung transplantation assisted by double ECMO had been accomplished successfully on a recipient with COVID-19, who was supported by ventilator and ECMO, with other organs function basically normal. The operation took 405 min and went smoothly. The cooperation and management guidelines of the operation room included the following: setting up of COVID-19 emergency operation group quickly; listing and preparing of the detailed operation supplies; transferring of the whole system of lung transplantation operating room in Wuxi People's Hospital to the Wuxi No.5 People's Hospital (isolation hospital); reconstruction of a negative pressure operating room for lung transplantation; formulating and strictly implementing the guidelines and management process for the operation of patient with COVID-19.

Review Article

Research progress on human herpesvirus 6 infection after liver transplantation

Liu Min, Sun Liying

2020, 11(4): 502-507, 515. doi: 10.3969/j.issn.1674-7445.2020.04.014

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Human herpesvirus 6 (HHV-6) may establish lifetime latency after initial invasion of the host, and liver transplant recipients may experience reactivation of latent infection during immunosuppression. HHV-6 infection in liver transplant recipients could lead to fever, hepatitis, encephalitis and graft dysfunction, and indirectly increases the risk of progression of liver fibrosis due to cytomegalovirus (CMV), hepatitis C virus (HCV) infection. At present, the pathogenesis of HHV-6 infection after liver transplantation has not been systematically elucidated, and effective prevention and treatment strategies are still lacking. This article provided a review for the research progress on the pathogenesis, risk factors, diagnosis and treatment of HHV-6 infection after liver transplantation.

Klotho: a potential protective protein for renal graft

Zhuang Jinyang, Liu Dong, Deng Gengguo, Wang Xiao

2020, 11(4): 508-515. doi: 10.3969/j.issn.1674-7445.2020.04.015

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Klotho gene is an anti-aging gene that is highly expressed in the kidney. Its encoding product Klotho protein can inhibit inflammation, oxidative stress injury, and apoptosis in renal tissue. It is regarded as a renal protective protein and expected to be a new target for the treatment of renal diseases. This article reviewed the biological characteristics of Klotho and the protective effect of Klotho on renal graft function.

Research progress on intestinal flora and renal transplantation

Qin Hao, Zhang Jian, Lin Jun

2020, 11(4): 516-520, 532. doi: 10.3969/j.issn.1674-7445.2020.04.016

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In recent years, with the gradual improvement of people's understanding of intestinal flora, exploring common complications after renal transplantation from the perspective of intestinal flora has become a research hotspot. Studies have demonstrated that the composition of the intestinal flora in renal transplant recipients has significant differences before and after surgery, and this difference is closely related to the occurrence and development of many complications after renal transplantation such as infection, rejection, diarrhea and so on, which could affect the prognosis of the recipients. This article reviewed the research progress on intestinal flora and renal transplantation in order to provide new treatment ideas and strategies for renal transplant recipients.

Effect and research progress on continuous hypothermic machine perfusion in preservation of renal graft

Zhang Fei, Liao Guiyi

2020, 11(4): 521-525. doi: 10.3969/j.issn.1674-7445.2020.04.017

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Inevitable ischemia-reperfusion injury (IRI) occurred in organ donation after citizen's death often results in delayed graft function (DGF) after renal transplantation. Although the incidence of DGF had reduced to some extent due to continuous hypothermic machine perfusion (HMP) for renal graft using LifePort, DGF of renal graft remains a major clinical problem. In order to further reduce the incidence of DGF after renal transplantation, renal transplant surgeons should fully understand the role of continuous HMP in renal transplantation, continue to conduct more in-depth basic and applied research. This article mainly summarized the effect of continuous HMP on renal transplantation and its research progress.

Research progress on molecular markers related to the donor kidney injury from organ donation after citizen's death

Han Fei, Sun Qiquan

2020, 11(4): 526-532. doi: 10.3969/j.issn.1674-7445.2020.04.018

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Shortage of donor kidney is a major problem in renal transplantation. Accurate evaluation of donor kidney function may reduce the organ rejection rate and save more patients with uremia. Compared with pathological examination, detection of circulating molecular markers is more convenient in clinical application. In this article, the research progress on the markers of kidney injury, such as serum creatinine, serum cystatin C (Cys-C), neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP), mitochondrial DNA (mtDNA), kidney injury molecule-1(KIM-1) and interleukin -18 (IL-18), were briefly reviewed.