Living donor liver transplantation in maple syrup urine disease – Case series and world's youngest domino liver donor and recipient

MSUD occurs due to deficiency of enzyme BCKAD required for metabolism of leucine, isoleucine, and valine leading to the accumulation of these and their ketoacids causing acute metabolic decompensation manifesting as encephalopathy or sudden death. The patient requires special protein‐restricted diet to survive. As this enzyme is expressed in liver, liver transplantation has been successfully performed as a cure. We report two patients of MSUD who underwent LDLT while their livers were used as a domino graft for other biliary cirrhotic patients. A 22‐month‐old male child diagnosed as a case of classic MSUD underwent LDLT from an altruistic aunt as donor following which his serum leucine levels normalized on an unrestricted protein diet. His liver was used as a domino graft. A 38‐month‐old female child with diagnosed MSUD underwent LDLT from a swap donor, and her liver was used as a domino graft. Her DQ improved post‐transplant. LDLT from non‐heterozygous donors is a cure for classical MSUD. Their livers can be used as domino grafts for non‐MSUD cases.     

An alternative method of arterial reconstruction in pediatric living donor liver transplantation with the recipient right gastroepiploic artery

The classical method for arterial reconstruction in pediatric living donor liver transplantation using left lateral segment consists of end-to-end anastomosis between the donor left hepatic artery and the recipient right hepatic artery. In the present case, an intra-operative hepatic artery thrombosis occurred because of extensive intima wall dissection of the recipient hepatic artery. The patient was a 6-yr-old boy with fulminant hepatic failure, who underwent living donor partial liver transplantation with left lateral segment from his father. The graft was irrigated by a left hepatic artery and an accessory left hepatic artery from gastric artery, both arteries with diameter of <2 mm. These arteries were anastomosed to the recipient right and left hepatic arteries, respectively. Before performing the bile duct reconstruction it was noted that these anastomoses were occluded by clots of blood. An extensive subintimal dissection of the recipient hepatic artery was the cause of this problem. The creation of a new anastomosis by using a more proximal part of this artery without subintimal dissection was judged impossible. Then, the right gastroepiploic artery was mobilized and an anastomosis was performed with the donor left hepatic artery in an end-to-end fashion. Arterial blood flow to the graft was established successfully and the patient's postoperative recovery was excellent. Fifteen days after the transplantation, an angiotomography demonstrated a good hepatic arterial blood flow. The patient is now alive and well, 4 months after the transplantation. In conclusion, the method of hepatic graft arterialization described here is an important option for patients who undergo living donor or split liver transplantation.     

Waiting list mortality for pediatric deceased donor liver transplantation in a Japanese living‐donor–dominant program

Living donor liver transplantation (LDLT) has become a major life‐saving procedure for children with end‐stage liver disease in Japan, whereas deceased donor liver transplantation (DDLT) has achieved only limited success. The annual number of pediatric liver transplantations is approximately 100‐120, with a patient 20‐year survival rate of 81.0%. In 2005, the liver transplantation program at the National Center for Child Health and Development in Tokyo, Japan, was initiated, with an overall number of 560 pediatric patients with end‐stage liver disease to date. In July 2010, our center was qualified as a pediatric DDLT center; a total of 132 patients were listed for DDLT up until February 2019. The indications for DDLT included acute liver failure (n = 46, 34.8%), metabolic liver disease (n = 26, 19.7%), graft failure after LDLT (n = 17, 12.9%), biliary atresia (n = 16, 12.1%), and primary sclerosing cholangitis (n = 10, 7.6%). Overall, 25.8% of the patients on the waiting list received a DDLT and 52.3% were transplanted from a living donor. The 5‐year patient and graft survivals were 90.5% and 88.8%, respectively, with an overall waiting list mortality of 3.0%. LDLT provides a better survival compared with DDLT among the recipients on the DDLT waiting list. LDLT is nevertheless of great importance in Japan; however, it cannot save all pediatric recipients. As the mortality of children on the waiting list has not yet been reduced to zero, both LDLT and DDLT should be implemented in pediatric liver transplantation programs.     

Very small pediatric donor kidney transplantation in pediatric recipients

Kidneys from very small pediatric donors (age <5 years, weight <21 kg) may be a means to increase the donor pool for pediatric recipients. Transplantation of small pediatric kidneys is more commonly performed in adult recipients due to the increased risks of technical complications, thrombosis, and early graft failure. While these risks are abrogated in adult recipients by limiting the donor weight to ≥10 kg and using the EB technique, it is unknown whether pediatric recipients achieve comparable results. US national data were assessed for all first‐time, deceased‐donor, kidney‐only pediatric recipients, 1/1996‐10/2013, who received very small pediatric donor grafts or grafts from ideal adult donors. We identified 57 pediatric EB, 110 pediatric SK, and 2350 adult transplants. The primary outcome was 3‐year all‐cause graft survival. Kaplan‐Meier curves showed worse outcomes for pediatric grafts compared to adult ideal grafts (P=.042). On multivariate analysis, pediatric recipients of SK grafts had significantly higher HRs (aHR 2.01, 95% CI 1.34‐3.00) and pediatric recipients of EB grafts had somewhat higher non‐significant HRs (1.57; 95% CI 0.88‐2.79) for graft survival. These results suggest cautionary use of very small pediatric donors as a source to expand the donor pool for pediatric candidates.     

Impact of hepatic arterial hemodynamics in predicting early hepatic arterial thrombosis in pediatric recipients younger than three yr after living donor liver transplantation

We used Doppler US to evaluate the changes in hepatic arterial hemodynamics that occur following LDLT in pediatric recipients, with a view to assessing the utility of these parameters in predicting early HAT. A retrospective review of 144 pediatric recipients (73 males, 71 females) who underwent routine Doppler US in the first week after LDLT was undertaken, and changes in hepatic arterial hemodynamics were assessed. The HARI and HAPSV were compared in patients with early HAT (defined as occurring in the first postoperative week) and a control group, and the utility of these parameters in predicting early HAT after LDLT was determined. A total of 11 pediatric recipients experienced early HAT, being diagnosed on average four and a half days after LDLT. HARI and HAPSV values were significantly different between the early HAT group and controls. HARI values <0.6 on the day before the onset of early HAT were able to predict HAT development with a sensitivity of 81.8% and specificity of 95.2%. This provides evidence for routine Doppler US examination in these patients and supports consideration of more intensive anticoagulation in these high‐risk patients.     

Lymphocytotoxic crossmatch in pediatric living donor liver transplantation

Abstract:  To investigate the relationship between the pretransplant LCT results and the outcome after pediatric LDLT in a single center. The clinical data of 76 children undergoing 79 LDLTs including three retransplantations from May 2001 to January 2006 were retrospectively analyzed. All of the children had end-stage liver disease, and their median age was 1.4 yr (range, six months to 16.5 yr). Immunosuppressive therapy consisted of cyclosporine- or FK-based regimens with steroids. The children were classified into two groups (positive or negative) according to the pretransplant LCT results. The incidences of post-transplant surgical complications and of rejection episodes were compared. The relationship between the pretransplant LCT results and patient and graft survival rates was also analyzed. Seventy-nine pretransplant crossmatch tests were done; 13 (16.5%) were positive, and 66 (83.5%) were negative. No significant difference was found in the pretransplant clinical factors between two crossmatch groups. There was no significant difference between the groups in the incidence of vascular and biliary tract complications, in the rate of early or steroid-resistant cellular rejections, or in one- and three-yr patient (91.7%, 91.7%, respectively, in the positive group, 93.5%, 93.5%, respectively, in the negative group, p = 0.80) and graft (92.3%, 92.3%, respectively, in the positive group, 88.8%, 86.4%, respectively, in the negative group, p = 0.63) survival. The present study demonstrates that there is no reason to do pretransplant LCT to select the living donor for pediatric LDLT.     

Liver graft volumetric changes after living donor liver transplantation with segment 2 graft for small infants

Urahashi T, Mizuta K, Sanada Y, Wakiya T, Yasuda Y, Kawarasaki H. Liver graft volumetric changes after living donor liver transplantation with segment 2 graft for small infants. Abstract: LT for small infants weighing <5 kg with liver failure might require innovative techniques for size reduction and transplantation of small grafts to avoid large‐for‐size graft, but little is known about post‐transplant graft volumetric changes. Five of 172 children who underwent LDLT received monosegment or reduced monosegment grafts using a modified Couinaud’s segment II (S2) graft for LDLT. Serial CT was used to evaluate the changes in the GV and other factors before LDLT and one and three months after LDLT. The shape of these grafts was classified into an OL type and an LL type. The GV increased in all patients one month after LDLT, whereas the GV decreased three months after LDLT in OL in comparison with one month after LDLT. The GRWR of the OL type has tended to decrease at three months, whereas the LL type showed a continuous increase with time, but finally they had adapted graft size for their body size. In conclusion, the volume of S2 grafts after LDLT had unique changes toward the ideal volume for the child weight when they received the appropriate liver volume.     

Reducing the incidence of hepatic artery thrombosis in pediatric liver transplantation: Effect of microvascular techniques and a customized anticoagulation protocol

We aimed to assess the incidence of HAT over three eras following implementation of microvascular techniques and a customized anticoagulation protocol in a predominantly cadaveric split liver transplant program. We retrospectively reviewed pediatric liver transplants performed between April 1986 and 2016 and analyzed the incidence HAT over three eras. In E1, 1986‐2008, each patient received a standard dose of 5 U/kg/h of heparin and coagulation profiles normalized passively. In E2, 2008‐2012, microvascular techniques were introduced. In E3, 2012‐2016, in addition, a customized anticoagulation protocol was introduced which included replacement of antithrombin 3, protein C and S, and early heparinization. A total of 317 liver transplants were completed during the study period, with a median age of 31.7 months. In E1, 22% of grafts were cadaveric in situ split grafts, while the second and third eras used split grafts in 59.0% and 64.9% of cases, respectively. HAT occurred in 9.5% in the first era, 11.5% (P=.661) in the second, and dropped to 1.8% in the third era (P=.043). A routine anticoagulation protocol has significantly reduced the incidence of HAT post‐liver transplantation in children in a predominantly cadaveric in situ split liver transplant program.     

Better innovate than compromise: A novel hepatic outflow reconstruction technique in pediatric living donor liver transplantation

Pediatric LDLT using donors with unfavorable vascular anatomy is challenging in terms of donor safety, and complexity of reconstruction in the recipient. We describe an innovative technique of hepatic venous outflow reconstruction involving the recipient RHV, in the presence of a rudimentary RHV in the donor. The postoperative course of the donor and recipient was uneventful with satisfactory venous outflow in both. This technique avoided the use of prosthetic material, an important consideration given the recipient age and requirement for growth. This shows that donors previously considered unsuitable for donation can be utilized safely as long as principles of vascular anastomosis are adhered to. Moreover, it highlights that innovation is sometimes necessary to avoid compromise in donor safety.     

International survey on anticoagulation and antiplatelet strategies after pediatric liver transplantation

In pediatric LT, anticoagulants and antiplatelet agents are regularly used to reduce the risk of vascular thrombosis. As evidence for optimal strategy is lacking, local practices vary greatly. The present survey aimed to compile an international overview of anticoagulation and antiplatelet strategies in pediatric LT. An online survey was sent to 98 pediatric LT centers in North and South America, Europe, Asia, and Australia. Twenty‐four centers answered the survey. 20/24 (83%) use some sort of anticoagulation and antiplatelet therapy, yielding 20 different strategies. Perioperative vascular problems, size of the hepatic artery, and patient weight were the most frequent determinants of changes in anticoagulant and antiplatelet strategy. Early HAT rates were reported to be 5% or less in 79% of responding centers. Anticoagulation and antiplatelet strategies were not significantly associated with early HAT rates (P = 0.63), or with the number of pediatric LTs performed per year and center (P = 0.92). Internationally, there is a wide variety in anticoagulation and antiplatelet strategies after pediatric LT. Efforts must be made to design a prospective multicentric trial to identify the optimal antithrombotic strategy.     

Impact of donor–recipient sex match on long‐term survival after heart transplantation in children: An analysis of 5797 pediatric heart transplants

The effect of donor–recipient sex matching on long‐term survival in pediatric heart transplantation is not well known. Adult data have shown worse survival when male recipients receive a sex‐mismatched heart, with conflicting results in female recipients. We analyzed 5795 heart transplant recipients ≤18 yr in the Scientific Registry of Transplant Recipients (1990–2012). Recipients were stratified based on donor and recipient sex, creating four groups: MM (N = 1888), FM (N = 1384), FF (N = 1082), and MF (N = 1441). Males receiving sex‐matched donor hearts had increased unadjusted allograft survival at five yr (73.2 vs. 71%, p = 0.01). However, this survival advantage disappeared with longer follow‐up and when adjusted for additional risk factors by multivariable Cox regression analysis. In contrast, for females, receiving a sex‐mismatched heart was associated with an 18% higher risk of allograft loss over time compared to receiving a sex‐matched heart (HR 1.18, 95% CI: 1.00–1.38) and a 26% higher risk compared to sex‐matched male recipients (HR 1.26, 95% CI: 1.10–1.45). Females who receive a heart from a male donor appear to have a distinct long‐term survival disadvantage compared to all other groups.     

Low incidence of hepatic artery thrombosis after pediatric liver transplantation without the use of intraoperative microscope or parenteral anticoagulation

The risk of hepatic artery thrombosis (HAT) after pediatric liver transplantation (PLT) has been reported to range from 0 to 25%. We report our experience focusing on the interrelationships between risk factors, surgical technique and the incidence of HAT after liver transplantation in the pediatric age group. From February 18, 1997 to December 31, 2003, 150 consecutive liver transplants were performed in 132 pediatric patients. There were similar numbers of whole grafts when compared with partial grafts, 80 (53.3%) vs. 70 (46.7%), p = 0.30. Four grafts (2.7%) developed HAT. Of the grafts with HAT, three were successfully revascularized within the first 24 h. Only one graft (0.66%) was lost to HAT. A single surgeon utilizing 3.5-6.0 magnification loupes performed all but one hepatic arterial anastomoses. All patients were followed postoperatively by a daily ultrasound protocol and with anticoagulation of aspirin and alprostadil only. Living and deceased donor left lateral segment grafts had an increased rate of HAT when compared with whole liver grafts. HAT with subsequent graft loss may be minimized in PLT with the use of surgical loupes only, anticoagulation utilizing aspirin, alprostadil, and daily ultrasounds.     

A case of pediatric live‐donor liver transplantation with a left lateral segment reduction by a linear stapler after reperfusion

In pediatric LDLT, graft reduction is sometimes required because of the graft size mismatch. Dividing the portal triad and hepatic veins with a linear stapler is a rapid and safe method of reduction. We herein present a case with a left lateral segment reduction achieved using a linear stapler after reperfusion in pediatric LDLT. The patient was a male who had previously undergone Kasai procedure for biliary atresia. We performed the LDLT with his father's lateral segment. According to the pre‐operative volumetry, the GV/SLV ratio was 102.5%. As the patient's PV was narrow, sclerotic and thick, we decided to put an interposition with the IMV graft of the donor between the confluence and the graft PV. The graft PV was anastomosed to the IMV graft. The warm ischemic time was 34 min, and the cold ischemic time was 82 min. The ratio of the graft size to the recipient weight (G/R ratio) was 4.2%. After reperfusion, we found that the graft had poor perfusion and decided to reduce the graft size. We noted good perfusion in the residual area after the lateral edge was clamped with an intestinal clamp. The liver tissue was sufficiently fractured with an intestinal clamp and then was divided with a linear stapler. The final G/R ratio was 3.6%. The total length of the operation was 12 h and 20 min. The amount of blood lost was 430 mL. No surgical complications, including post‐operative hemorrhage and bile leakage, were encountered. We believe that using the linear stapler decreased the duration of the operation and was an acceptable technique for reducing the graft after reperfusion.     

The relationship of donor source and age on short- and long-term allograft survival in pediatric renal transplantation

Abstract:  Limited pediatric data on allograft survival from advanced aged kidney donors exist. To determine the influence of donor source and age on allograft survival in pediatric renal transplant recipients, we analyzed the OPTN database. Allograft survival for 7291 pediatric renal transplants was evaluated. Up to five yr post-transplantation, graft survival was higher for LD vs. DD recipients. At seven yr, allograft survival was 71% in 18–54 yr-old LD recipients, 59.1% in ≥55 yr-old LD, and 45.1% in ≥50 yr-old DD recipients. An approximate 35% improvement in allograft survival in 18–54 yr-old LD recipients was observed. Multivariate results showed that recipients of LD 35–49 (aRR 0.66, 95% CI 0.55–0.80) and LD 50–54 (aRR 0.65, 95% CI 0.45–0.94) have a graft survival advantage over the ideal DD. In LD ≥55 yr, no improvement in graft survival was observed when compared with the 18–34 yr-old DD. In summary, we observed in a pediatric population, <55 yr-old LD kidneys afford improved long-term allograft survival when compared with DD kidney recipients. Increasing awareness of the long-term graft survival advantage for children receiving an LD kidney, even from older donors, should be a priority.     

Hepatic artery reconstruction in pediatric living donor liver transplantation under 10 kg, without microscope use

Enne M, Pacheco-Moreira L, Balbi E, Cerqueira A, Alves J, Valladares MA, Santalucia G, Martinho J-M. Hepatic artery reconstruction in pediatric living donor liver transplantation under 10 kg, without microscope use.
Pediatr Transplantation 2010: 14: 48–51. © 2009 John Wiley & Sons A/S.
Abstract:  Arterial reconstructions are pivotal, particularly in pediatric LDLT. We describe microsurgical reconstruction technique with 6× loupes and the clinical course of the first 23 less than 10 kg recipients in an initial LDLT program at a developing country. From March 2002 to October 2008, 286 liver transplantation were performed in 279 patients at our unit. There were 73 children and 206 adults. Among the children, 23 weighing less than 10 kg were recipients from living donors. Arterial reconstructions were with end-to-end interrupted suture using a 6× magnification loupe, according to the untied suture technique. All patients were prospectively followed by color Doppler ultrasound protocol. In our initial experience there were no arterial complications. With mean 24 months of follow-up, 19 patients (82%) are alive with good graft function. Hepatic artery in LDLT can be safely reconstructed with microsurgical techniques without microscope using, with 6× loupe magnification, and can achieve good results in patients under 10 kg.     

Technique advance to avoid hepatic venous outflow obstruction in pediatric living‐donor liver transplantation

HVOO represents a serious critical complication of pediatric living‐donor liver transplantation because open surgical repair is virtually impossible. Currently, despite several technical innovations and the introduction of triangulated anastomosis for hepatic vein reconstruction, the reported incidence of HVOO is still considerable. The aim of this study was to propose a new technique for hepatic venous reconstruction that avoids the original orifice of the recipient hepatic veins. Instead, anastomosis is performed in a newly created wide longitudinal orifice in the anterior wall of the recipient inferior vena cava. A total of 210 living related‐donor liver transplantations were performed using two methods for reconstruction of the hepatic vein. Group 1 included 69 patients subjected to direct anastomosis of the orifice of the graft hepatic vein and a wide orifice created in the recipient inferior vena cava by the confluence of the orifices of the right, left, and middle hepatic veins. Group 2 included 141 patients in whom the original orifices of the recipient hepatic veins were closed, the inferior vena cava was widely opened, and a long longitudinal anastomosis was performed using two lines of continuous sutures. Diagnosis of HVOO was suspected based on clinical findings and ultrasound studies and then confirmed by liver biopsy and interventional radiology examinations. Among the 69 recipients in group 1, 16 patients died due to graft problems during the postoperative period and eight of the survivors (15.1%) presented with HVOO. In group 2 (141 patients), 21 patients died, and there were no cases of HVOO. A comparison of the incidence of HVOO between groups revealed a significant difference (p = 0.01). Hepatic venous reconstruction during pediatric living‐donor liver transplantation should be performed using a wide longitudinal incision in the anterior wall of the recipient inferior vena cava because this technique eliminated anastomosis complications.