Influence of CYP3A5 genotype of donor and recipient on tacrolimus concentration/dose ratio in early postoperative period of children living related liver transplantation / 中华器官移植杂志

Objective To provide a reference for the individualized medication of tacrolimus in children after living related liver transplantation,according to the effect of CYP3A5 genotyping on the concentration/dose ratio of tacrolimus in children with living related liver transplantation.Methods Peripheral blood samples were collected from children with living related liver transplantation in the transplant center.The CYP3A5 genotype was determined by polymerase chain reaction (PCR)pyrosequencing.Related indicators such as tacrolimus dose and concentration in children with living related liver transplantation were collected within 3 months after operation.According to the donor/receptor genotype,the donor/receptor expression group,the donor/receptor single expression group,and the donor/receptor non-expression group were set up.Tacrolimus concentration/dose (C0/D) ratio was statistically analyzed at 5th day,7th day,14th day,28th day,2nd month and 3rd month after administration.Results Among the 76 patients,there were 21 patients (27.63％) in CYP3A5 donor/receptor non-expression group,27 patients (35.53％) in donor/receptor single expression group,and 28 patients (36.84％) in the donor/receptor expression group.The time to the target concentration range (C0＞8 ng/mL) in CYP3A5 donor/receptor expression group was longer than in donor/receptor single expression group and donor/receptor non-expression group.Except for the individual time points,there were significant differences between CYP3A5 donor/receptor expression group and donor/receptor non expression group,or between donor/receptor non-expression group and donor/receptor single expression group,or between donor/receptor expression group and donor/receptor single expression group at rest time points (P＜0.05 for all).Conclusion In the CYP3A5 donor/receptor gene expression group,the higher dose was needed to reach the target concentration range than the gene single expression group and the donor/receptor non-expression group.Except for individual time points,there were significant differences in C0/D at rest different time points.Regardless of whether the donor or recipient contained the CYP3A5* 1 allele,C0/D was lower than the non-expressed type of the gene.Considering the polymorphism of the donor/receptor CYP3A5 gene,it was worthful for children with living related liver transplantation to allow the drug concentration to reach the therapeutic window as soon as possible and reduce organ rejection and adverse reactions.

The donor mortality in living related liver transplantation / 中华肝胆外科杂志

To investigate the cause of donor death in living donor liver transplantation(LDLT), we reviewed all published articles in English on LDLT from the Foreign Medical Journal Full-Text Service (FMJS) and searched the literature for donor deaths before 2008. We identified 12 donor deaths. The rate of donor death is 0.2%. Any donor death would be a catastrophe for the donor's family and for the medical team. It is imperative to avoid donor death in LDLT.

Study for Histopathologic Findings of the Hepatic Artery in the Living Related Liver Transplantation Patients

Living related liver transplantation(LRLT) is theoretically the best treatment option for end stage liver disease and nonresectable hepatocellular carcinomas. Anastomosed hepatic artery is at high risk in thrombosis after LRLT, which directly related to the patient's life. Usually, recipient hepatic artery is so friable and intimal separation and blood clot between intima and media were noted frequently. From December 2001 to June 2003, consecutive 30 hepatic arteries were harvested from 45 LRLTs patients with end stage liver disease. All hepatic artery were anastomosed with #9-0 nylon by plastic surgeon. All hepatic arteries were patent intraoperatively and postoperatively. In the histopathologic study of hepatic artery, some had intimal thickening, myxoid change and intimal hyperplasia in 14 out of 30 cases. Since pathologic changes may develop as a result of transarterial chemoembolization(TACE) and others causes, we postulated that the prevalence of hepatic arterial thrombosis, a catastrophic graft-threatening complication of LRLT, might be increased in this subset of LRLT patients who received TACE. But, in our study, patients who underwent hepatic arterial chemoembolization statistically do not show an increased risk of developing hepatic arterial thrombosis or other hepatic arterial complications after LRLT. And pathologic changes are statistically not correlate with the TACE.

Does the Venovenous Bypass influence Coagulation Status in Living-Related Liver Transplantation? / 대한마취과학회지

BACKGORUND: Venovenous bypass (VVB) in liver transplantation has been used to decrease the acute hemodynamic and metabolic changes during anhepatic periods. But, the use of VVB in patients undergoing liver transplantation is still under debate concerning its relative risks and benefits. Therefore, the aim of this study was to examine the influences of VVB on the coagulation status and the amount of transfusion in living-related liver transplantation. METHODS: We conducted this retrospective study on 39 patients who underwent orthotopic living-related liver transplantation using the piggyback technique from March 2001 to April 2002. While 19 patients did not receive venovenous bypass, 20 patients received. We compared the two groups in terms of coagulation-related parameters (prothrombin time, activated partial thromboplastin time, platelet count, fibrinogen and thromboelastograph), the amount of transfusion during intraoperative and post-operative 1day. We also compared the incidences of post-reperfusion syndrome in the two groups. RESULTS: The group that underwent living-related liver transplantation with VVB required more packed red blood cell (p-RBC) transfusion than the other group without VVB from post-reperfusion untill the end of operation (P<0.05). This difference in the amount of p-RBC transfusion may be due to the blood remained in the VVB circuit at the termination of VVB. However, the two groups were similar in terms of coagulation-related parameters, the amount of other blood components, such as fresh frozen plasma, platelet concentrates, cryoprecipitate, total amount of transfusion during the 24 hours post- operatively, and the incidence of post-reperfusion syndrome. CONCLUSiONS: We conclude that the using of venovenous bypass in living-related liver transplantation did not influence coagulation status and the amount of transfusion perioperatively.

Living-Related Liver Transplantation with Heterozygote Carrier Graft in Children with Wilson Disease / 대한소아소화기영양학회지

PURPOSE: The purpose of this study was to evaluate the efficiency of treatment of living-related liver transplantation (LRLT) with the parental heterozygote carrier graft in children with Wilson disease. METHODS: We retrospectively evaluated 7 children with Wilson disease who had received liver transplantation from 1994 to 2002 at Asan Medical Center. All the donors were parental. Liver functions, Kayser-Fleischer ring, and other factors regarding to copper metabolism were analyzed. RESULTS: Of the 7 children, 5 had fulminant hepatitis and 2 had decompensated liver cirrhosis irresponsive to medical therapy. All donors being parental, all grafts came to be heterozygote carrier grafts. Survival rate was 100% in those 7 children, 87% in all children with liver transplantation in the same period, and 84% in children with non-metabolic liver disease. After liver transplantation, all 7 children could stop low copper diet and penicillamine therapy and their AST, total bilirubin and prothrombin time were recovered to normal. After liver transplantation, ceruloplasmin and serum copper levels were also recovered to normal. A marked reduction in 24 hr-urinary copper excretion was observed in all recipients after transplantation. During follow-up, Kayser-Fleischer rings resolved completely after LRLT in 5 children and partially in 1 child. CONCLUSION: We concluded that living-related liver tranplantation in children with Wilson disease with parental heterozygote carrier graft is an effective treatment modality.

Donor Safety in Living Donor Liver Transplantation Using Right Lobe / 대한이식학회지

PURPOSE: Right lobe donation is technically more difficult and need to define surgical technique and has more risk for surgical complication. Right lobe donation usually matched graft size but safety of donor is major concern. In this paper, we reviewed our experience of donor hepatectomy using right lobe in regarding to safe of our donor operations, retrospectively. METHODS: Retrospective analysis of 42 donor operations for adult LDLT using right lobe was performed. We observed the patient characteristics, the operative findings, peak liver enzymes (AST, ALT, bilirubin) as donor risk and mortality, morbidity. RESULTS: The peak value of liver enzymes in the group of less the 30% of remained liver were significantly higher than the group of more than 30% of remained liver and these values could induced the risk on donor. The postoperative peak value of liver enzymes were increased according to degree of fatty change especially in case of more than 10% fatty change even without significance. We observed the liver regeneration on postoperative 3 months and the regeneration of liver volume on postoperative 3 months was about two times compare to preoperative value and the regenerative activity was more increased in the group of less amount of remained volume. There was no donor mortality and most important complication was biliary complication, in which were biliary injury, bile leakage and biliary stricture. CONCLUSION: Right lobectomy for donor operation requires a meticulous surgical technique to minimize donor morbidity. Right lobectomy can be performed safely with minimal risk in case of careful donor selection that the remained liver volume exceed 30% of the total liver volume and the liver of minimal fatty change.

Analysis of Linear Growth in Children after Living-related Liver Transplantation / 대한소아소화기영양학회지

PURPOSE: The aim of this study is to evaluate the effective role of living-related liver transplantation (LRLT) on posttransplant linear growth in children. METHODS: Thirty six children were enrolled who received LRLT at Asan Medical Center from December, 1994 to February, 1999 and showed more than one-year postoperative survival. Mean height standard deviation score (zH) was analyzed according to medical records including heights during pretransplant and posttransplant follow-up periods. RESULTS: zH of total children showed significant linear growth after LRLT from -1.58 to 0.33 at 24 posttransplant month (p<0.05). zH in children under 6 years of age, to exclude the effect of adolescent linear growth spurt, showed increment in height (p<0.05). Linear growth of children with liver cirrhosis improved and that with fulminant hepatitis was matained same. While stunted children (mean zH=-2.30) achieved good catch-up growth after transplantation, children with normal growth remained same. Children with significant hepatic dysfunction after LRLT such as chronic rejection or posttransplant lymphoproliferative disorder showed retarded posttrasplant linear growth. There was no statistical difference according to the type of immunosuppressants. CONCLUSION: LRLT resulted in adequate or catch-up linear growth in children with acute, chronic and metabolic liver disease. Successful LRLT suggested to be a promising option not only in long term survival but also in normal linear growth.

Right Hepatic Lobectomy for Adult Living Donor Liver Transplantation Safety, anatomical points, and technical points

BACKGROUND: Living related liver transplantation (LRLT) has gained acceptance as treatment modality for children with end-stage liver disease. The left lobe used in LRLT doesn't provide adequate parenchymal mass for its application to adults. We have used right lobe for LRLT in adults. Some criticism has been aroused becuase of the potential significant risk to the donors. METHODS: We analyzed the surgical risk and the stress to 20 donors in a right lobectomy for LRLT. We also analyzed anatomical points for safe harvest, and we describe techincal points based on anatomical variations. RESULTS: There were no deaths, and 6 major complications (3 bleeding, 1 perihepatic fluid collection, 1 pleural effusion, and 1 bile peritonitis after removal of the T-tube) occurred in 6 patients. Liver function was normalized within 2 weeks. There were anatomical variations in the hepatic vein, the portal vein, and the bile duct, especially the right inferior hepatic vein (55%), trifurcation of the portal vein (10%), low inserion of the right posterior bile duct into the common hepatic duct (10%), and separate insertion of the right anterior bile duct and right posterior bile duct into the hepatic duct (10%). We made a vena cava patch for the right inferior hepatic vein. In cases of the low insertion of the right posterior hepatic duct into the common hepatic duct, the cholecystectomy should be done carefully so as not to injure the right posterior hepatic duct. We ligated and divided the right posterior bile duct before dissection of the hepatic artery and the portal vein. In cases of trifurcation of the portal vein, closure of the left portal vein should be done to prevent the narrowing of the left portal vein lumen. CONCLUSIONS: Our results suggest that a right lobectomy for LRLT is safe for donors. However, anatomical variations in the bile duct, the hepatic vein, and the portal vein should be kept in mind to ensure a safe and successful operation.

An Experience of Living Related Liver Transplantation Showed Hepatic Artery Stenosis Postoperatively

Liver transplantation is an accepted and successful mode of treatment for pediatric end-stage liver disease. A living related liver transplatation(LRLT) in a child has certain potential advantages, such as short cold ischemic time, accurate graft size, and vessel diameter match based on elective preoperative preparations. Recently, microvasular surgery techniques have been introduced in hepatic artery reconstruction but still the possibility of hepatic artery thrombosis remains. Herein, We report an LRLT case, which showed hepatic artery stenosis postoperatively, successfully dilated by balloon angioplasty technique.

Anesthetic Experience for Liver Transplantation in Children from a Living Related Donor: 3 reports / 대한마취과학회지

We managed three cases of anesthesia for living related liver transplantation from December 1994 to July 1995. Donors were recipient's parents and two of them were 35-year old man, the other was 25-year-old woman. The recipients were suffered from congenital liver diseases (two of them were diagnosed as biliary atresia and the other Byler's disease). They had presented severe jaundice and cholangitis and their mean age & body weight were 15 +/- 4.9 months and 8.6 +/- 1.22 kg, respectively. Average duration of anesthesia was about 15 hours, and anhepatic time was 140 minutes, 80 m inutes and 50 minutes, respectively. Careful attention was paid to body temperature, serum potassium, ionized calcium, blood coagulation function, as well as to general condition and respiratory function. Hemodynamic value was relatively stable through out the operation and postoperative mechanical ventilatory support was required for about 3 days.

Living Related Liver Transplantation / 대한이식학회지

Human orthotopic liver transplantation was first attempted in 1963. Living related liver transplantation has been introduced by Raia in 1988. In children, biliary atresia is the leading indication of living related liver transplantation. We performed 2 cases living related liver transplantation on May, 1996. The donors were 32 and 30 year old father, recipients were his 3 year old son and 4 year old daughter. The causes of liver failure were drug induced fulminant hepatitis and recurrent cholangitis due to biliary atresia. The first case was incompatible of ABO blood typing, donor AB(Rh+) and recipient B(Rh+). The ABO incompatible donor was performed preoperatively plasmapheresis. After left lateral segmentectomy of donor and total hepatectomy of recipient, donor liver was orthotopically transplanted. The average operation time of donor and recipient were 8 hours and 12.5 hours. The amount of transfusion in donor and recipient were average 2 pints and 2.5 pints. The perioperative immunosuppression was maintained with prednisone, azathioprine and cyclosporin, but 1st case was changed from cyclosporin to OKT3 on postoperative 9th day. The postoperative complications of recipient were pulmonary edema, bacterial and fungal infection. The donors were discharged on postoperative 8th and 9th day. The first case patient was discharged postoperative 42th day due to respiratory complication. The 2nd recipient was discharged postoperative 22th day. We suggested that living related liver transplantation is good modality for resolving the graft shrtage in pediatric liver transplantation.

Living Related Liver Transplantation Across ABO Blood Groups / 대한이식학회지

To overcome the shortage of available organ in children, living-related liver transplantation(LRLT) has been introduced in Asan Medical Center since 1994. However, the use of graft livers across ABO blood groups is unavoidable since the organ donor is usually one of the recipient's parents in LRLT cases. In ABO-incompatible liver transplants from brain dead donors, the incidences of perioperative mortality, arterial thrombosis, and irreversible rejection and the rate of retransplantation have been reported to be greater. But recent reports from LRLT showed that 1-year survival rate of ABO incompatible cases were approximately 80%. So we started ABO incompatible LRLTs at our institute since Feb, 1996. Three cases of ABO incompatible LRLT have been performed thereafter, 2 with fulminant hepatitis and 1 with cirrhosis. Plasma pheresis or exchange transfusion was done to decrease isohemagglutinin perioperatively. Immunosuppression consisted of a quadruple-drug treatment in one, FK506 and steroid in two. The follow-up periods were 2, 4 and 13 months respectively. One child died of acute respiratory distress syndrome with normal graft function on 51st postoperative day. Two children are alive with good health, but one of them suffers S2 segment bile duct stricture, which is under the management with PTBD. The present results suggest that ABO incompatilbe LRLTs can be performed to overcome the shortage of the liver in children using a combination of the preioperative plasma pheresis and immunosuppression.