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The aim of this study is to present our institutional experience in living donor liver transplantation (LDLT) as a treatment for end-stage liver disease in children with biliary atresia (BA). A retrospective review of transplant records was performed. One hundred BA patients (52 males and 48 females) underwent LDLT. The mean follow-up period was 85.5 months. The mean age was 2.4 years. The mean preoperative weight, height, and computed GFR were 12.2 kg, 82.5 cm, and 116.4 ml/min/1.73 m2, respectively. Twenty-seven patients were below 1 year of age, and 49 patients were below 10 kg at the time of transplantation. Ninety-six had had previous Kasai operation prior to transplant. The mean recipient operative time was 628 min. The mean recipient intraoperative blood loss was 176 ml. Thirty-five did not require blood or blood component transfusion. The left lateral segment (64) was the most common type of graft used. There were 27 operative complications which included 3 reoperations for postoperative bleeding, 9 portal vein, 4 hepatic vein, 4 hepatic artery, and 7 biliary complications. There was one in-hospital mortality and one retransplantation. The overall rejection rate was 20%. The overall mortality rate was 3%. The 6-month, 1-year and 5-year actual recipient survival rates were 99%, 98% and 98%, respectively.

Background: Liver graft size, anatomy of the bile duct and the vascular inflow and outflow are essential for living related liver transplantation (LRLT). Preoperative delineation of those variations that would change the operative procedure to achieve a successful result especially in an emergency condition., Purpose: Our aim was to develop a rapid and noninvasive imaging diagnostic method for the detection of anatomical variants that is mandatory for a safe operation when selecting potential liver transplant living donors. We used a different magnetic resonance (MR) imaging technique, which enabled to us to exploit the anatomical landmark of the liver, signal enhancement of blood flow in the abdomen, and the intrahepatic biliary routes inside the liver. Then, with the help of Advantage Window workstation reconstruction, the reconstructed single vascular or biliary systems were displaced in a three-dimensional fashion and the whole examination finished within 30 min., Methods: Modification of the standard MR technique was performed on a superconductive 1.5T whole body image scanner, MR arteriogaphy, venography, and cholangiography with three-dimensional reconstruction in evaluating the anatomy of the hepatic arteries, hepatic veins, portal venous system, bile ducts, and liver size in potential liver transplant living donors. These anatomical structures were compared with traditional imaging methods., Results: In all 38 cases, as well as delineation of the portal vein detail to the segmental level was satisfactorily obtained in this MR study. The images were well displayed in a three-dimensional fashion, which had good correlation with images from traditional imaging modalities and operative findings. In 86.8% cases, the MR arteriography was well matched with the celiac angiography. Of those 17 operative cases, estimation of liver volume was well correlated with the liver graft within 3.9-12.5% variation. In the major hepatic vein, we obtained 100% accuracy and 88.2% in the minor branches. Of 12 donors received intraoperative cholangiography during liver donation, good correlation of biliary anatomy was achieved. One donor was excluded from graft donation due to the complicated arterial supply to the left liver. According to the anatomical variation, surgical procedures in graft harvesting and anastomosis were readjusted and no major complications were found in those donors and all recipients survived after liver transplantation., Conclusion: MR volumetry, venography, angiography, and cholangiography with three-dimensional reconstruction is sufficient for all major imaging evaluation. It may replace the traditional conventional catheter angiography, computed tomography, sonography and endoscopic retrograde cholangiography as a single investigation in the evaluation of the potential liver transplant donors. Angiography is only valuable in suboptimal cases and intraoperative cholangiography is only performed in biliary ductile variants.

Postoperative biliary and vascular complications contribute significantly to morbidity and mortality in liver transplantation. Interventional radiologists are an integral part of the multidisciplinary team necessary for optimizing the management of these complications. During a 15-year period, 39 cadaveric and 25 living related liver transplantations were performed at the Chang Gung Memorial hospital, Taiwan. Of 64 liver transplant recipients, 9 (3 adult and 6 pediatric) underwent 13 interventional radiological procedures for the treatment of biliary sludge-casts (n = 2), bile duct occlusion or stenosis (n = 2), hepatic veins thrombosis (n = 1), hepatic veins stenosis (n = 1), portal vein stenosis with splenorenal shunting (n = 1), biloma (n = 1), and infected fluid collection or ascites (n = 4). Antegrade or retrograde interventional approach was used to successfully treat all biliary complications, and all percutaneous drainage procedures were effective in the control of intra-abdominal fluid collections. Portal vein stenosis was treated by balloon dilatation, and the associated splenorenal shunt was closed by metallic coil embolization via transhepatic catheterization of the portal vein. Hepatic vein stenosis was effectively treated by balloon dilatation and expandable metallic stent deployment via transfemoral and jugular venous approaches, respectively. Hepatic vein thrombosis was only partially lysed by transvenous streptokinase administration, and surgical thrombectomy was needed to achieve complete recanalization. The total success rate of the interventional procedures was 92 % with no procedure-related complications. The overall survival rate in this series is 89 %, and all patients who underwent living related liver transplantation maintain to date a 100 % survival rate. We can conclude that interventional radiological procedures are very useful for managing biliary and vascular complications after liver transplantation. These techniques provide a cure in most situations, thus obviating the need for further surgical intervention or re-transplantation.

Background: Biliary tract reconstruction has long been considered the Achilles' heel of liver transplantation as biliary complications can increase morbidity and mortality especially in partial liver graft transplantation., Methods: Thirty-four living related liver transplants were performed at Chang Gung Memorial Hospital in Kaohsiung for 33 children and 1 adolescent during a 5.5-year period. All potential donors underwent a detailed preoperative imaging study of the vascular and biliary anatomy, including three-dimensional helical computed tomographic cholangiography (n = 20), magnetic resonance cholangiography (n = 14), and intra-operative cholangiography (n = 31) before graft retrieval. All hepatic artery anastomoses were performed in the standard microsurgery fashion and their patency was confirmed intra-operatively using Doppler ultrasound., Results: The biliary complication rate was 8.8% (3/34), including multiple intrahepatic biliary stenosis of unknown origin (n = 1), bile leakage from the Roux-en-Y loop (n = 1), and a missed biliary radicle (n = 1) which were treated via interventional radiological and surgical procedures. The overall graft and patient survival rates were 100%., Conclusion: The biliary complication rate in this series was low compared to those of other experienced centers. Complete study of the variations of intrahepatic duct ramification pre-and-intra-operatively provided adequate information on the appropriate transection plane. Furthermore, intra-operative Doppler ultrasound verification of vessel patency helps prevent vascular complications, which has been identified as a cause of biliary complications.

Spontaneously accepted mouse liver allografts are capable of protecting subsequently transplanted donor organs from rejection; however, the underlying mechanisms are unclear. Dendritic cells (DC) residing in liver grafts are likely important in tolerance induction. DC propagated from mouse liver with GM-CSF are phenotypically and functionally immature. They are poor allostimulators in MLR and prolong survival of pancreatic islet allografts. It has been problematic to perform mechanistic studies in an islet transplant model because of difficulties in obtaining sufficient graft infiltrating cells. In this study, we used a sponge allograft model [i.e.. a subcutaneously implanted sponge matrix loaded with B10 (H2b) spleen cells]. To investigate the influence of administration of donor (B10) liver-derived DC on alloimmune reactivity of C3H (H2k) hosts, sponge graft infiltrating cells (SGIC) and recipient spleen cells were isolated, and their immunophenotype and donor-specific cytotoxic T lymphocyte (CTL) activity were examined. The results illustrate that donor-specific CTL activity of T cells are lower in recipients that had received systemic treatment with liver-derived immature DC, associated with a decrease in CD8+ cell population and an increase in Gr-1+ cells in SGIC, compared with recipients treated with mature bone marrow (BM)-derived DC. Interestingly, administration of liver DC directly into the sponge did not inhibit T cell responses. These data suggest that systemic administration of donor liver DC induces donor-specific hyporesponsiveness, probably not by direct inhibition of graft infiltrating T cells. The increased Gr-1+ cells may play immune regulatory roles in induction of host donor-specific hyporesponsiveness.

Background: Hepatic venous reconstruction is critical in living donor liver transplantation because outflow obstruction may lead to graft dysfunction or loss. We describe our experience and analyze outcomes with a technique of creating a single outflow tract using venoplasties of the graft and recipient hepatic veins., Patients and Methods: A retrospective study was done on 38 consecutive living donor liver transplants performed from June 1994 to March 2000. The grafts included 36 left-side grafts and 2 right-side grafts. Nine grafts had multiple hepatic veins and required a venoplasty of two or three hepatic veins to create a single outflow orifice. Triple recipient hepatic venoplasty was performed in 32 patients, double venoplasty in 5 and none in 1., Results: There were four cases of outflow obstruction, three occurring in patients with a double recipient venoplasty. Two of the problems were remedied intraoperatively by adjusting the position of the graft although two were structural in nature and required the insertion of expandable metallic vascular stents. All donors and recipients with their original grafts are alive at a mean follow-up period of 27 months., Conclusion: A triple recipient venoplasty with a matching venoplasty of multiple graft hepatic veins to create a single wide outflow orifice is recommended in living donor liver transplantation using left side grafts.

The donor shortage problem is particularly serious in Asia and has markedly limited progress in liver transplantation. The increasing demand has, in fact, made it necessary to resort to living donor liver transplantation in both pediatric and adult recipients. Nevertheless, expanding the use of split liver allografts is yet another option to increase the supply. This has a wide potential application on a regional level because most liver transplant programs are still small and may have limited resources in terms of being able to do two transplants in one sitting. The first experience of overseas sharing of split liver grafts in Asia took place in January 1999. The graft was from a 35-yr-old donor from Kaohsiung, Taiwan, who sustained irreversible brain damage in a vehicular accident and had optimal conditions for multiorgan donation. The liver was split ex vivo and the left lateral segment was given to a 3-yr-old girl with biliary atresia at the Chang Gung Memorial Hospital. The extended right lobe split graft was transported to Hong Kong and transplanted into a 51-yr-old male patient with end-stage hepatitis C cirrhosis who was then in a state of acute failure with hepatorenal syndrome. Graft function was excellent in both recipients and the patient from Taiwan was discharged without any complications. Unfortunately, the Hong Kong recipient developed a cerebrovascular accident and required a reoperation for bile leakage from the cut surface of the liver in the early postoperative period. He has made a steady recovery since then; graft function has remained good and his kidneys have recovered. Both patients are currently alive and well 11 months post-transplant. This initial experience of overseas sharing of split liver grafts in Asia demonstrates its feasibility. It has a potentially wide applicability and could lead to the establishment of a formal organ-sharing network in the region. Established competence and mutual trust among the participating liver transplant teams would be essential in perpetuating such a graft-multiplying strategy on an organized basis.

Little is known about the possible role of complement inhibitors on tolerance induced by liver allografts. Clusterin, which is a plasma glycoprotein, inhibits cytolytic membrane attack complex (MAC) of complement by binding to soluble C5b-7 complex. The role of clusterin in relation to the naturally achieved tolerance in a rat orthotopic liver transplantation (OLT) has not been investigated before. Here we determined the kinetics of clusterin expression at different post-transplantation time points in a tolerogenic model (DA-PVG) where rejection was naturally overcome without any immunosuppressive drugs in comparison with the syngenic OLT model (DA-DA). Peripheral blood and liver tissues were taken from OLT at various post-operative time points. A strong expression of soluble clusterin was observed on post-transplantation day 7, which occurred at the peak of the rejection in this tolerogenic OLT model. The expression of clusterin remained strong even after tolerance was achieved. The intensity of clusterin expression was much stronger when compared with the syngenic OLT (DA-DA) model after OLT. A strong expression of clusterin mRNA was also observed in the tolerogenic model on post-OLT day (POD) 7 and the expression persisted when compared with the syngenic model on post-OLT day 60. Our data have shown that the strongest levels of clusterin during the reaction phase in tolerogenic OLT may be involved in tolerance induction.

We report two cases of unusual repeated hypotension, decreased cardiac output, decreased mixed venous oxygen saturation, decreased central venous pressure, pulmonary artery pressure, and pulmonary wedge pressure after the completion of all vascular anastamoses of liver transplantation. These unstable hemodynamics appear to reflect a clinically relevant picture of hypovolemia. However, the real cause was partial hepatic outflow obstruction. The obstruction was suspected because hypotension was alleviated by elevating the full-sized liver graft ventrally and to the left. Doppler ultrasound examination confirmed that the flow velocity of the hepatic vein outflow was insufficient when the liver fell to its resting position in the right hepatic fossa. An additional side-to-side cavo-caval anastomosis resolved the problem in one patient, whereas the other required not only the additional anastomosis, but also application of a tissue expander filled with 770 mL normal saline beneath the liver to eliminate the obstruction. We emphasize that obstruction of the hepatic outflow causes only temporal hypovolemia because of a decrease of venous return and that treatment of this complication should be surgical intervention to relieve the obstruction. Blind resuscitation with fluids will not solve the problem and, in fact, may result in fluid overload with subsequent complications.

The purpose of this study was to evaluate the outcome of the medial segment of the graft after living related liver transplantation (LRLT). Of the 12 pediatric recipients who underwent LRLT, 2 received whole left liver graft, 1 left lateral segment graft, and 9 extended left lateral segment grafts. The hepatic veins of the donor were reviewed and the volume of the medial segment and left lateral liver was measured before and 6 months after liver transplantation. The flow velocity and direction of the portal vein in the medial segment graft was also evaluated by Doppler ultrasound. The grafted livers of all recipients showed a substantial increase in volume of 9-120% 6 months after LRLT. For the left lateral segment, an increase in volume was found in all cases ranging from 21 to 245%. For the medial segment, volume increases of 5-48% were found in seven cases with normal hepatopetal flow detected inside the segment 4 intrahepatic portal vein. In four cases, the partial medial segment graft of the extended left lateral liver graft decreased in volume from 33 to 69%. Among these four cases, slow flow (n = 2) and hepatofugal flow (n = 1) were also detected in the intrahepatic portal vein of the medial segment. Mapping of the tributary of the hepatic veins of the graft revealed inadequate venous drainage of the partial segment 4 graft, which may be considered as the cause of the atrophic change of the partial segment 4 graft. In conclusion, different regenerative rates between the left lateral segment and the medial segment were noted, with a greater rate in the left lateral segment. The venous drainage of the medial segment is of primary concern in the determination of the outcome of the regeneration. Atrophic change occurs when inadequate hepatic venous drainage is encountered. Therefore, if an extended left lateral liver graft is required, the corresponding draining veins of the partial medial segment must be preserved. Otherwise, whole left liver or left lateral segment graft would be a better choice.

The purpose of this study was to determine the utility of intraoperative Doppler ultrasound for the diagnosis and reduction of the vascular complications in liver transplantation. This study included 19 pediatric and 5 adult patients. In the pediatric group, 12 patients received living related liver transplantation (LRLT), two splitting liver transplantation (SLT), three reduced-size liver transplantation (RLT) and two full-size pediatric liver transplants (FPLT). The hemodynamics and waveform of the hepatic vein, portal vein and hepatic artery were evaluated by intraoperative Doppler ultrasound (US) after reperfusion of the graft. Unsatisfactory hemodynamics was identified in nine cases, including decrease hepatic venous flow (6-9 cm/s) with non-pulsative flat waveform (adults, n = 2 and LRLT, n = 2); portal vein thrombosis (LRLT, n = 1); decrease portal flow (8 mL/min/kg) (LRLT, n = 1); occlusion of the portal vein (SLT, n = 1); poor arterial flow with dampened artery waveform (FPLT, n = 2). These abnormalities were all successfully re-reconstructed by surgical procedures and achieved a graft survival rate of 100%. Two late vascular complications including hepatic venous thrombosis and recurrent portal vein stenosis with splenorenal shunt were discovered 1 month later. They were treated effectively by surgical thrombolectomy and percutaneous balloon dilatation and metallic coils embolization respectively. Three patients died of non-vascular complications and all patients who underwent LRLT survived with a resultant 87.5% overall survival rate. In conclusion, intraoperative Doppler US is efficient in detecting abnormal hepatic hemodynamics, which permits early intervention and hence a better prognosis for the patients. Re-reconstructive procedures were monitored closely under Doppler US guidance until proper flow and wave-form were established. This reduces post-transplant vascular complications and thereby eliminates the likelihood of a lethal complication that might call for re-transplantation.

Lymphoproliferative disorder (LPD) is a well recognized complication of solid organ transplantation. It is associated with Epstein-Barr virus (EBV) infection and is often a fatal complication of immunosuppression. We report a 2.5-year-old boy who developed LPD presenting as small bowel lymphoma after liver transplantation. The patient had intermittent fever after transplantation and reactivation of latent EBV infection was documented by pre- and posttransplant serologic tests. About 5 months after his liver transplantation, the patient had sudden onset of abdominal pain and emergency laparotomy was performed for peritonitis. He proved to have multiple small bowel perforations caused by B cell lymphoma and died of multiple organ failure 9 days after operation, despite aggressive treatment and stopping immunosuppressive agents. We conclude that prevention of overimmunosuppression in pediatric recipients after liver transplantation and early detection and treatment of LPD are important to decrease this often-fatal complication.

Living related liver transplantation (LRLT) has been developed in response to the paediatric organ donor shortage. According to the International Living Donor Registry, 521 transplants had been performed in 515 patients between December 8 1988 and January 19 1996 in 30 centres worldwide. The overall actuarial patient and graft survival rates were 82.7 and 80%, respectively. Between June 17 1994 and November 30 1996, the authors performed 11 LRLT at the Chung Gung Memorial Hospital. The living donors consisted of 10 mothers and one father. The mean graft weight was 303 g and the mean graft recipient weight ratio was 2.2%. Donor hepatectomy was performed without vascular inflow occlusion. The intra-operative blood loss ranged from 30 mL to 120 mL with an average of 61 mL, and blood transfusion was not required in all donors both intra-operatively and during the postoperative period. Underlying diseases of the recipients were biliary atresia (n = 10) and glycogen storage disease (n = 1). The mean graft cold ischaemia time was 106 min, the mean second warm ischaemia time was 51 min and the mean interval between portal and arterial reperfusion was 81 min. The initial LRLT results were promising with all donors having been discharged without complication. The recipients experienced a few complications, all of which were manageable with early intervention. All 11 recipients are alive and well. These are encouraging results and the authors hope to expand the use of live donors for liver transplantation to cope with demand.

In liver transplantation, the role of the imaging study in the evaluation of transplant candidacy is to define the conditions in which transplantation is contraindicated and to identify anatomic variations that may alter the surgical approach. Among pediatric recipients, the largest numbers of patients were suffering from biliary atresia, and metabolic diseases. Acquired and congenital vascular anomalies are usually associated with biliary atresia which may be hazardous to liver transplantation requiring a modification of standard surgical procedure. Therefore, confirmation of the patency of the vascular structure is the most essential prerequisite especially in living related liver transplantation. From June 17, 1994 to November 30, 1996, eleven living related liver transplantations were performed at Chang Gung Memorial Hospital, Kaohsiung Medical Center. The left liver or the left lateral segment of the liver was used as the graft. It is necessary to keep patency of the inflow and outflow of hepatic vessels and biliary trees of both donor and recipient. Both resected and remnant livers have to function well postoperatively. In order to achieve parenchyma dissection with minimal hepatic damage, various anatomical variations of the liver size, portal vein, hepatic veins and bile duct of the donor cannot be ignored. Therefore, the precise preoperative anatomical evaluation of the donor using various imaging modalities is mandatory for the safe partial liver transplantation. Ultrasound, computed tomography, magnetic resonance image and three dimensional computed tomographic cholangiography are the method of choice in demonstrating the anatomical structures. After the complex anatomical factors can be well evaluated we can assess the appropriateness and feasibility of the procedure that may correct problems during or after transplantation. Finally, noninvasive and safe examination procedures are our outmost concern and policy in doing this survey.

Recognition of rejection and other hepatic complications by needle biopsy plays a significant role in the management of liver allograft recipients. In this report, 22 pediatric patients (below 18 years old) were selected from the 37 liver transplants. Seven of the 22 cases have an uneventful posttransplant course. The most common cause of allograft injury in these patients appeared to be acute cellular rejection. It occurred in 7 (31.8%) of the 22 cases and was the primary process in 8 of the 25 episodes of liver dysfunction. Other etiologies, such as opportunistic viral infection (3 cases), biliary obstruction (2 cases), preservation injury (1 case), and vascular obstruction (1 case) were less common. Acute graft rejection causing liver dysfunction was associated with a mixed portal inflammation, destruction of the interlobular bile ducts, and varied degree of venous endotheliitis, followed by centrilobular hepatocyte necrosis. Chronic rejection was not seen in our pediatric cases. Cold ischemic injury causing transient graft dysfunction as seen in one of our patients demonstrated focal, limited areas of hepatocyte necrosis, mild centrilobular hepatocyte ballooning, and cholestasis without evidence of bile duct damage. More severe ischemic injury resulted from vascular complication causing diffuse hepatocyte necrosis was seen in one patient with hepatic vein thrombosis. The histologic patterns observed were not pathognomic; however, liver biopsies were helpful in suggesting the probable cause of liver dysfunction and in predicting subsequent allograft recovery when used in conjunction with clinical information, radiologic, and other laboratory tests.

Between March 1984 and August 1994, 13 orthotopic liver transplantations were performed in 13 patients < or = 25 years of age. The indications included Wilson's disease (n = 7), biliary atresia (n = 4), choledochal cyst (n = 1) and hepatitis C cirrhosis (n = 1). Technical variants included full-size (n = 11), reduced-size (n = 1) and living-related (n = 1) liver transplantation. These recent technical innovations have offered an expanded donor pool for earlier transplantation, shorter waiting times and excellent quality grafts. Surgical complications occurred in six patients; all required additional surgery. Biliary complications were encountered more commonly in our earlier patients. Our actuarial patient and graft survival rate is 92% at 2 years. The long-term follow-up of our liver-transplanted Wilson's disease patients provides confirmatory evidence that orthotopic liver transplantation cures the underlying metabolic defect with complete normalization of biochemical abnormalities of copper metabolism, reversal of neurological impairments and the disappearance of Kayser-Fleischer corneal rings. The high rate of patient survival and excellent rehabilitation indicate that with prudent clinical judgement, liver transplantation can be achieved with an acceptable rate of morbidity, mortality and cost in a setting where manpower and donor organs are very limited.