Liver transplantation for inherited metabolic liver diseases / 器官移植

Inherited metabolic liver disease (IMLD) is a category of liver metabolic diseases caused by genetic disorders. The pathogenesis of IMLD is complex, which primarily comprises the accumulation of harmful metabolic substrates or products caused by specific enzyme defects and energy defects or abnormal deposition caused by abnormal metabolism of glucose, fat and other substances. In recent years, liver transplantation has played an increasingly critical role in the treatment of IMLD with the development of liver transplantation. At present, IMLD has become the second most important indication after biliary atresia in pediatric liver transplantation. Currently, IMLD patients receiving liver transplantation can be divided into two categories: the first category is IMLD complicated with liver disease; Category 2 patients have a normal liver structure but are deficient in related metabolic enzymes. It can not only replace the liver with abnormal structure and function, but also provide normal enzymes required for patients' metabolism, which may improve their quality of life and even save their lives. In this article, common feasible liver transplantation for IMLD, clinical prognosis and surgical procedures of liver transplantation for IMLD were reviewed, aiming to provide reference for liver transplantation for IMLD.

Clinical value of split domino donor auxiliary liver transplantation / 中华消化外科杂志

Objective:To investigate the clinical value of split domino donor auxiliary liver transplantation.Methods:The retrospective and descriptive study was conducted. The clinco-pathological data of 3 liver transplantation recipients who were admitted to Nanjing Drum Tower Hospital affiliated to Nanjing University Medical School and 1 liver transplantation recipient who was admitted to external hospital in September 2018 were collected. The first case was male, aged 22 years, who was diagnosed as type II citrullinemia (CTLN2). The second case undergoing liver transplantation in external hospital was male, aged 59 years, who was diagnosed as decompensated alcoholic cirrhosis. The third case was female, aged 52 years, who was diagnosed as hepatocellular carcinoma of right lobe of liver. The fourth case was female, aged 51 years, who was diagnosed as hepatocellular carcinoma of right lobe of liver. The donor liver from a brain and cardiac death donor was split in vitro into the left liver and the right liver, in which the right liver without middle hepatic vein, and the modified piggyback liver transplantation using the left liver and the classical orthotropic liver transplantation using the right liver was conducted on the first and the second case, respectively. The original liver of the first case was split in vivo into the left liver and the right liver, and the piggyback auxiliary liver transplantation using the left liver and the piggyback auxiliary liver transplantation using the right liver was conducted on the third and the fourth case who underwent extended right hemihepatectomy, respectively. Observation indicators: (1) intraoperative situations; (2) follow-up. Follow-up was conducted using outpatient examination and telephone interview to detect liver function, liver imaging, complication and survival of recipients up to October 2021.Results:(1) Intraoperative situations. Liver transplantation was conducted successfully on the first, third and fourth case, with the operation time, the volume of intraoperative blood loss, the donor liver cold ischemia time, the graft-to-recipient weight ratio were 400 minutes, 370 minutes, 390 minutes, 600 mL, 1 300 mL, 1 600 mL, 230 minutes, 152 minutes, 135 minutes, 1.2%, 0.8%, 1.1%. (2) Follow-up. B-ultrasound examination of the first, third and fourth case after liver transplantation showed that the blood flow was normal, and all the 3 cases discharged and were followed up at postoperative 1, 6 and 12 month. The liver function, the level of blood ammonia and citrulline were normal of the first, third and fourth case at postoperative 1 week. Imaging examina-tion showed normal liver morphology of the first and third case, and a transplanted liver atrophy caused by portal vein steal of the fourth case. ① The level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), direct bilirubin (DBil) of the first case before liver transplantation, at postoperative 1 day, 2 day, 3 day, 7 day, 10 day, 6 month and 1 year were 22.8 U/L, 404.1 U/L, 355.5 U/L, 289.6 U/L, 31.0 U/L, 23.1 U/L, 42.1 U/L and 25.8 U/L, 31.5 U/L, 517.7 U/L, 327.6 U/L, 172.9 U/L, 15.9 U/L, 21.4 U/L, 47.5 U/L and 29.7 U/L, 3.8 μmol/L, 92.1 μmol/L, 87.4 μmol/L, 79.7 μmol/L, 90.1 μmol/L, 130.6 μmol/L, 33.8 μmol/L and 25.4 μmol/L, 2.3 μmol/L, 47.0 μmol/L, 44.1 μmol/L, 47.1 μmol/L, 57.4 μmol/L, 70.9 μmol/L, 24.7 μmol/L and 9.7 μmol/L, respectively. The level of citrulline and blood ammonia of the first case before and after liver transplantation were 999.0 μmol/L, 196.0 μmol/L and 14.6 μmol/L, 9.0 μmol/L, respectively. The first case was followed up for 3 years and survived without any liver transplantation related complication. ② The level of ALT, AST, TBil, DBil of the third case before liver transplantation, at postoperative 1 day, 2 day, 3 day, 7 day, 10 day, 6 month and 1 year were 21.3 U/L, 143.9 U/L, 182.0 U/L, 132.0 U/L, 17.2 U/L, 10.1 U/L, 17.6 U/L and 16.8 U/L,20.0 U/L, 291.0 U/L, 227.5 U/L, 106.4 U/L, 15.8 U/L, 10.8 U/L, 17.1 U/L and 19.4 U/L, 6.8 μmol/L, 50.9 μmol/L, 45.0 μmol/L, 34.0 μmol/L, 32.4 μmol/L, 22.3 μmol/L, 12.8 μmol/L and 14.9 μmol/L, 2.5 μmol/L, 18.4 μmol/L, 17.2 μmol/L, 14.9 μmol/L, 14.8 μmol/L, 12.1 μmol/L, 3.6 μmol/L and 4.4 μmol/L. The level of citrulline and blood ammonia of the third case after liver transplantation were 24.9 μmol/L and 16.0 μmol/L. The third case was followed up for 3 years and survived without any liver transplantation related complication. ③ The level of ALT, AST, TBil, DBil of the fourth case before liver transplantation, at postoperative 1 day, 2 day, 3 day, 7 day, 10 day, 6 month and 1 year were 35.0 U/L, 268.7 U/L, 682.0 U/L, 425.8 U/L, 57.5 U/L, 34.0 U/L, 29.4 U/L and 18.1 U/L, 37.0 U/L, 419.1 U/L, 436.2 U/L, 139.5 U/L, 35.2 U/L, 32.4 U/L, 54.7 U/L and 32.8 U/L, 7.1 μmol/L, 64.2 μmol/L, 41.4 μmol/L, 17.6 μmol/L, 34.2 μmol/L, 48.7 μmol/L, 14.1 μmol/L and 21.8 μmol/L, 2.8 μmol/L, 18.9 μmol/L, 16.1 μmol/L, 6.0 μmol/L, 14.6 μmol/L, 26.7 μmol/L, 3.9 μmol/L, 11.8 μmol/L. The level of citrulline and blood ammonia of the fourth case after liver transplantation were 8.4 μmol/L and 47.0 μmol/L. One week after surgery, the transplanted right liver of the fourth case occurred atrophy due to blood stealing from the right branch of the portal vein. B-ultrasound examination showed that the reflux of the hepatic artery and hepatic vein was unobstructed. Immunosuppressants were discontinued 3 months after operation on the fourth case and there was no complication such as rejection, bile leakage, biliary stricture, thrombosis and vascular stricture during follow-up. The fourth case died of lung metastasis 19 months after operation.Conclusion:Split domino donor auxiliary liver transplantation can be used for the treatment of metabolic liver disease and advanced hepatocellular carcinoma.

Current status and prospect of surgical technique of liver transplantation / 器官移植

Along with the increasing quantity of patients with end-stage liver diseases year by year, as an efficacious treatment, the safety and efficacy of liver transplantation are critical issues to be considered. In addition, liver transplant techniques have become a new research hot spot. In recent years, liver transplant techniques are constantly innovating and developing with the unremitting efforts of researchers. Researchers have successively developed multiple liver transplant techniques, such as split liver transplantation, ischemia-free liver transplantation, liver xenotransplantation, domino liver transplantation, delayed total hepatectomy combined with liver resection and segment Ⅱ-Ⅲ liver transplantation, heterotopic auxiliary liver transplantation on splenic fossa and magnetic anastomosis. It has laid a foundation for expanding the donor pool, improving clinical efficacy of liver transplantation and enhancing the quality of life of liver transplant recipients. In this article, the exploration, development, innovation and improvement of liver transplant techniques were reviewed and prospected, aiming to provide reference for clinical application of liver transplantation.

Surgical technical innovations in pediatric liver transplantation / 器官移植

In recent decade, pediatric liver transplantation has developed rapidly in China due to the improvement of surgical techniques and postoperative management, which has been applied from several domestic liver transplantation centers to more than 10 provinces, cities and autonomous regions. The annual quantity of pediatric liver transplantation has exceeded 1 000 for 3 consecutive years, ranking first across the world. The technique of pediatric liver transplantation has been gradually oriented to precision medicine. The development of pediatric liver transplantation mainly focuses on the "grafts". In this article, the development characteristics and trends of pediatric liver transplantation were elucidated from the perspectives of different types of liver transplantation that expanded the source of donor liver, including split liver transplantation, auxiliary liver transplantation, Domino liver transplantation and liver transplantation with hyper-reduced grafts, as well as the application of minimally invasive surgical and microsurgical anastomosis techniques in pediatric liver transplantation, which represented by laparoscopic surgery and Da Vinci surgical system, aiming to provide reference for further improving the long-term survival rate of grafts and the quality of life of the recipients.

Mechanism of coagulation dysfunction in the recipients mediated by tissue factor activation after liver xenotransplantation / 器官移植

Objective To investigate the mechanism underlying the activation of tissue factor (TF) that leads to coagulation dysfunction in the recipients after liver xenotransplantation. Methods Auxiliary heterotopic liver xenotransplantation was performed in 3 minipigs with α-1,3-galactosyltransferase gene-knockout (GTKO) as the donors and Tibetan macaque (Macaca thibetana) as the recipients. Postoperative coagulation function changes in the recipients were observed. Reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical staining were adopted to quantitatively measure the expression levels of monkey and minipig TF messenger RNA (mRNA) and protein in the liver tissues of the primary and transplant livers at different time points before and after transplantation. The recalcification time of peripheral blood mononuclear cell (PBMC) was recorded in the normal control monkeys and the recipient monkeys before and 2 h after liver transplantation to evaluate the coagulation status in the recipients. Results All three recipients presented with different degrees of coagulation dysfunction after surgery, manifested as a decrease in fibrinogen level and a reduction in platelet count. The monkey TF protein was positively expressed in the primary livers after surgery, whereas negatively expressed in transplant livers before and after liver transplantation. The minipig TF protein was negatively expressed in both primary livers and transplant livers. At postoperative 2 h, monkey TF mRNA was up-regulated by (2.10±0.24) times in the primary liver compared with the preoperative level, whereas the minipig TF mRNA was up-regulated by (1.42±0.15) times compared with preoperative level. There was statistical significance between the primary livers and transplant livers (P=0.014). Compared with PBMC in the normal control monkeys and recipient monkeys before liver transplantation, the recalcification time of the PBMC in the recipient monkeys was significantly shortened at postoperative 2 h (both P<0.001). Conclusions At the presence of coagulation dysfunction after liver xenotransplantation, the level of TF activation in the primary livers is significantly higher than that in the transplant livers. The TF activation in the primary livers is the main cause of coagulation dysfunction after liver xenotransplantation.

A case of highly sensitized recipient after combined kidney transplantation and splenic fossa auxiliary heterotopic liver transplantation in a 28-months follow-up and review / 中华器官移植杂志

Objective To analyze the follow-up results and clinical characteristics of one case of highly sensitized recipient after combined kidney transplantation and splenic fossa auxiliary heterotopic liver transplantation.Methods This patient was diagnosed as having chronic renal insufficiency in the uremia period 10 years ago,subjected to kidney transplantation 9 years ago,and got renal allograft loss 8 years ago.The recipient was positive for PRA (for class Ⅰ,31％,and for class Ⅱ,63％).Under the general anesthesia,the patient was given combined kidney transplantation and splenic fossa auxiliary heterotopic liver transplantation.The ATG was used for immune induction.Rituximab and plasma exchange were applied to prevent acute rejection.Regular follow-up was done after discharge.Results On the postoperative day (POD) one,ALT was 256 IU/L,AST was 342 IU/L and serum creatinine was 502 μmol/L.On the POD 6,ALT and AST levels were normal and serum creatinine was 141 μmol/L.Serum creatinine increased to 202 μmol/L and the volume of urine reduced on the POD 7.The ultrasound displayed graft size increased slightly,substantial echogenicity enhanced,artery blood flow RI increased to 0.8,suggesting the occurrence of acute rejection.A single dose of Rituximab,intravenous IG,and plasma exchange were given.On the POD 60,serum creatinine was reduced to 131 μmol/L.During a follow-up period of 28 months,imrnunosuppresants were given:Tac + MMF + Pred.FK506 valley concentration was maintained at 6-8 μg/L.The function of the transplanted kidney and liver was normal,and the general conditions were good.Conclusion Combined kidney transplantation and splenic fossa auxiliary heterotopic liver transplantation is safe.Individualized medication and regular follow-up are the important factors for long-term survival of recipients.

Updates of heterotopic auxiliary liver transplantation with portal vein arterialization / 中华消化外科杂志

In recent years,liver transplantation donor shortage as one of world medical problems is paid more attention by domestic and overseas scholars.In view of that,heterotopic auxiliary liver transplantation emerges which transplants the whole or some parts of a donor liver outside the original liver position on the condition that some parts or the whole of the original liver were retained.As for the liver transplantation with poor conditions on portal vein,reconstruction of portal vein has become an aporia.Based on this,some scholars put forward the theory——arterialization of portal vein(PVA),namely a method to increase arterial blood supply or replace portal vein blood perfusion of liver by establishing some pathes among artery and portal vein or its branches.The research background and current situation of heterotopic auxiliary liver transplantation with portal vein arterialization,the transplanting position of donor liver,vessel reconstruction,dynamics mechanism after reconstruction and liver regene-ration are summarized in this review.

Advance on auxiliary liver transplantation / 国际外科学杂志

Auxiliary liver transplantation reserves whole or part of recipient' native liver while implanting the graft. It call be classified as auxiliary heterotopic liver transplantation and auxiliary orthotopic liver transplantation according to the location of the graft. On the basis of graft volume. it can be categorized as whole liver auxiliary liver transplantation and partial liver auxiliary liver transplantation. Either cadaveric or living donor is available. Because auxiliarg orthotopic liver transplantation is only the partial liver transplantation, so it is also called aunliry orthotopic partial liver transplantation. The. technique of auxiliary liver transplantation progresses with the devehopment of liver transplantation. Great attention is paid to auxiliary liver transplantation because of its special superiority, in spite of some unresolved problems.

Simple Auxiliary Liver Transplantation without Bile Duct Reconstruction in the Rat / 대한이식학회지

There has been numerous experimental liver transplantation models in the rodent : orthotopic versus hetrerotopic; whole liver versus partial liver; microvascular suture versus cuff method in technical aspects. Several simplified modifications were introduced for experimental liver transplantation for improving animal-survival rate. Liver transplantation without arterial reconstruction, the cuff tchnique or stent method were the examples of simplifing modification. In practice, complications related to biliary reconstruction are frequent causes of intraabdominal infection in our rat liver transplantation. Here we propose using simple liver transplantation model of partial heterotopic liver transplantation without artery and bile duct reconstruction in the studies which need only observation of immediate graft survival or very short-term follow-up. Here we examined the serial histologic changes of auxiliary liver grafts without biliary reconstruction during short period after transplantation. Until 7 days of transplantation, bile duct proliferation was confined in the portal area of grafts and did not distort the lobular structure. Early graft-survival and rapid immunologic response might be evaluated by this easy transplantation model.

Simple Auxiliary Liver Transplantation without Bile Duct Reconstruction in the Rat / 대한이식학회지

There has been numerous experimental liver transplantation models in the rodent : orthotopic versus hetrerotopic; whole liver versus partial liver; microvascular suture versus cuff method in technical aspects. Several simplified modifications were introduced for experimental liver transplantation for improving animal-survival rate. Liver transplantation without arterial reconstruction, the cuff tchnique or stent method were the examples of simplifing modification. In practice, complications related to biliary reconstruction are frequent causes of intraabdominal infection in our rat liver transplantation. Here we propose using simple liver transplantation model of partial heterotopic liver transplantation without artery and bile duct reconstruction in the studies which need only observation of immediate graft survival or very short-term follow-up. Here we examined the serial histologic changes of auxiliary liver grafts without biliary reconstruction during short period after transplantation. Until 7 days of transplantation, bile duct proliferation was confined in the portal area of grafts and did not distort the lobular structure. Early graft-survival and rapid immunologic response might be evaluated by this easy transplantation model.