John M. Ham

Right lobe living donor liver transplantation.

1. Living donor liver transplantation (LDLT) is currently performed at about 30 centers in the United States. 2. Careful and critical evaluation of donor and recipient is required for optimal outcome. 3. Right lobe donation is preferred over left lobe donation in adult LDLT. 4. There has been 1 donor death (<0.3%) in the US experiences. Donor biliary complications occur in approximately 4% of the cases. 5. Recipient survival after adult LDLT in the United States is approximately 88%. Hepatic artery thrombosis occurs in 3% and biliary complications in 18%.

Liver regeneration and function in donor and recipient after right lobe adult to adult living donor liver transplantation

BACKGROUND Regeneration of the liver to a predetermined size after resection or transplantation is a well described phenomenon, but the time course over which these events occur has not been well defined. It is not clear how initial liver mass, reperfusion, immunosuppression, or steatosis influence this process. METHODS Liver regeneration was assessed prospectively by volumetric magnetic resonance imaging (MRI) in living right lobe liver donors and the recipients of these grafts. Imaging was performed at regular intervals through 60 days after resection/transplantation, and liver mass was determined. Liver function tests and synthetic function were monitored throughout the study period in donors and recipients of these grafts as well as recipients of cadaveric grafts. RESULTS MRI consistently overestimated liver mass by a mean of 45 g (+/-65) (range 10-123). Donor liver mass increased by 101%, 110%, 115%, and 144% at 7, 14, 30, and 60 days after resection, respectively. Recipient liver mass increased by 87,101, 119, and 99% at 7, 14, 30, and 60 days after transplantation, respectively. Steatosis did not influence the degree of regeneration or graft function, nor was there a functional difference between grafts of >1% graft to recipient body weight ratio or <1%. CONCLUSIONS MRI accurately determines right lobe mass. Most liver regeneration occurs in the 1st week after resection or transplantation, and the time course does not differ significantly in donors or recipients. The mass of the graft or remnant segment affects the duration of the regeneration process, with a smaller initial liver mass prolonging the course. Steatosis of <30% had no bearing on liver function or regeneration and, therefore, should not be an absolute criterion for exclusion of donors. A calculated graft to recipient body weight ratio of 0.8% is adequate for right lobe living donor liver transplantation.

Selection and Outcome of Living Donors for Adult to Adult Right Lobe Transplantation

BACKGROUND The shortage of cadaveric livers has sparked an interest in adult-to-adult living donor transplantation. Right lobe donor hepatectomy is frequently required to obtain a graft of adequate size for adult recipients. Careful donor selection is necessary to minimize complications and assure a functional graft. METHODS A four-step evaluation protocol was used for donor selection and satisfactory results of all tests in each step were required before proceeding to the next. Donors were selected based on a battery of laboratory studies chosen to exclude unrecognized infection, liver disease, metabolic disorders, and conditions representing undue surgical risk. Imaging studies included ultrasonography, angiography, magnetic resonance imaging, and intraoperative cholangiography and ultrasonography. The information obtained from liver biopsy was used to correct the estimated graft mass for the degree of steatosis. RESULTS From March 1998 to August 1999, 126 candidates were evaluated for living donation. A total of 35 underwent donor right lobectomy with no significant complications. Forty percent of all donors that came to surgery were genetically unrelated to the recipient. A total of 69% of those evaluated were excluded. ABO incompatibility was the primary reason for exclusion after the first step (71%) and the presence of steatosis yielding an inadequate estimated graft mass after the second step (20%). CONCLUSIONS Donor selection limits the application of living donor liver transplantation in the adult population. Unrelated individuals increase the size of the donor pool. Right lobe hepatectomy can be performed safely in healthy adult liver donors. Preoperative liver biopsy is an essential part of the evaluation protocol, particularly when the estimated graft mass is marginal.

Results of the double-blind, randomized, multicenter, phase III clinical trial of thymoglobulin versus Atgam in the treatment of acute graft rejection episodes after renal transplantation

BACKGROUND Thymoglobulin, a rabbit anti-human thymocyte globulin, was compared with Atgam, a horse anti-human thymocyte globulin for the treatment of acute rejection after renal transplantation. METHODS A multicenter, double-blind, randomized trial with enrollment stratification based on standardized histology (Banff grading) was conducted. Subjects received 7-14 days of Thymoglobulin (1.5 mg/kg/ day) or Atgam (15 mg/kg/day). The primary end point was rejection reversal (return of serum creatinine level to or below the day 0 baseline value). RESULTS A total of 163 patients were enrolled at 25 transplant centers in the United States. No differences in demographics or transplant characteristics were noted. Intent-to-treat analysis demonstrated that Thymoglobulin had a higher rejection reversal rate than Atgam (88% versus 76%, P=0.027, primary end point). Day 30 graft survival rates (Thymoglobulin 94% and Atgam 90%, P=0.17), day 30 serum creatinine levels as a percentage of baseline (Thymoglobulin 72% and Atgam 80%; P=0.43), and improvement in posttreatment biopsy results (Thymoglobulin 65% and Atgam 50%; P=0.15) were not statistically different. T-cell depletion was maintained more effectively with Thymoglobulin than Atgam both at the end of therapy (P=0.001) and at day 30 (P=0.016). Recurrent rejection, at 90 days after therapy, occurred less frequently with Thymoglobulin (17%) versus Atgam (36%) (P=0.011). A similar incidence of adverse events, post-therapy infections, and 1-year patient and graft survival rates were observed with both treatments. CONCLUSIONS Thymoglobulin was found to be superior to Atgam in reversing acute rejection and preventing recurrent rejection after therapy in renal transplant recipients.

Surgical Management of Anatomical Variations of the Right Lobe in Living Donor Liver Transplantation

OBJECTIVE To review the anatomical variations of the right lobe encountered in 40 living liver donors, describe the surgical management of these variations, and summarize the results of these procedures. SUMMARY BACKGROUND DATA Anatomical variability is the rule rather than the exception in liver and biliary surgery. To make effective use of liver segments from living donors for transplantation, surgical techniques must be adapted to the anomalies. METHODS Donor evaluation included celiac and mesenteric angiography with portal phase, magnetic resonance angiography, and intraoperative ultrasonography and cholangiography. Arterial anastomoses were generally between the donor right hepatic artery and the recipient main hepatic artery. Jump-grafts were constructed for recipients with hepatic artery thrombosis, and double donor arteries were joined to the bifurcation of the recipient hepatic artery. The branches of a trifurcated donor portal vein were isolated during the parenchymal transection, joined in a common cuff, and anastomosed to the recipient main portal vein. Significant accessory hepatic veins were preserved, brought together in a common cuff if multiple, and anastomosed to the recipient cava. The bile ducts were individually drained through a Roux-en-Y limb, and stents were placed in most patients. RESULTS Forty right lobe liver transplants were performed between adults. No donor was excluded because of prohibitive anatomy. Seven recipients had a prior transplant and five had a transjugular intrahepatic portosystemic shunt (TIPS). Arterial anomalies were noted in six donors and portal anomalies in four. Arterial jump-grafts were required in three. Sixteen had at least one significant accessory hepatic vein, and one had a double right hepatic vein. There were no vascular complications. Multiple bile ducts were found in 27 donors. Biliary complications occurred in 33% of patients without stents and 4% with stents. CONCLUSIONS Anatomical variations of the right lobe can be accommodated without donor complications or complex reconstruction. Previous transplantation and TIPS do not significantly complicate right lobe transplantation. Microvascular arterial anastomosis is not necessary, and vascular complications should be infrequent. Biliary complications can be minimized with stenting.

The interrelationship between portal and arterial blood flow after adult to adult living donor liver transplantation

Background. When adults are transplanted with segmental grafts, disparity between the size of the graft and the native organ is almost universal.These grafts presumably still receive all of the native portal inflow despite a reduced vascular bed and dramatically elevated blood flow may result. The hemodynamic changes after segmental transplantation in adults have not yet been studied and their clinical significance is unknown. Methods. Portal venous and hepatic arterial blood flow were measured intraoperatively in right lobe liver donors and recipients with electromagnetic flow probes. Postoperative evolution was monitored in recipients with ultrasonography. Results. Portal flow to the right lobe ranged from 601 to 1102 ml/min before resection and from 1257 to 2362 ml/min after transplantation. There was a statistically significant linear correlation between the change in portal flow and graft to recipient body weight ratio. Arterial blood flow ranged from 213 to 460 ml/min before resection and from 60 to 300 ml/min after transplantation. Preoperative portal peak systolic velocity was uniformly around 10 cm/sec. Values on postoperative day 1 were increased to 30 cm/sec in recipients of cadaveric organs, to 50 cm/sec in recipients of organs with graft to recipient body weight ratios of more than 1.2%, and to 115 cm/sec in recipients of organs with ratios less than 0.9%. A decreasing tendency was universally observed. Arterial systolic velocity was inversely related to portal systolic velocity. Neither graft dysfunction nor vascular complications occurred. Conclusions. The hemodynamic pattern after right lobe transplantation is predictable and intraoperative measurements and ultrasonography are useful for monitoring. The size of the graft influences the magnitude of the hemodynamic changes.

The hepatic artery in liver transplantation.

Hepatic artery complications after liver transplantation are uncommon, but represent an important cause of morbidity and mortality. In addition, these complications tax an already limited supply of donor organs because of the frequent need for retransplantation in this group of patients. In this study, we examined the incidence of hepatic arterial anomalies in donors and recipients of orthotopic liver transplants, focusing on the techniques that are available for hepatic arterial reconstruction and on the occurrence of hepatic arterial complications. A total of 77 liver transplants were carried out in 68 patients. Standard recipient anatomy was present in 60 of 68 patients (88%). Anomalous vessels were identified in eight patients (12%), including six cases of replaced right hepatic artery (9%) and two cases of replaced left hepatic artery (3%). Donor liver arterial anatomy was standard in 62 cases (80%). Anomalous arterial supply was identified in 15 of 77 donor livers (20%), including replaced left hepatic artery in nine (12%) and replaced right hepatic artery in six (8%). A variety of methods were used to manage the anomalous vessels. There was one hepatic artery pseudoaneurysm, three cases of hepatic artery thrombosis (4%), and one patient developed a dissection of the native celiac axis. In primary transplants, utilization of the recipients proper hepatic artery was associated with a significantly higher risk of hepatic artery thrombosis (P less than 0.04) when compared with the common hepatic artery or the branch patch technique. Use of a Carrel patch on the donor artery was associated with a significantly reduced incidence of hepatic artery thrombosis (P less than 0.0003). For retransplantation, it is recommended that a more proximal recipient anastomotic site be chosen. An innovative method is described that provides increased length of the donor arterial supply without the use of an arterial graft.

Adult Living Donor Versus Deceased Donor Liver Transplantation: A 6‐Year Single Center Experience

No long‐term (>3 years) prospective comparison of adult‐to‐adult living donor liver transplantation (A2ALLTx) to adult deceased donor liver transplantation (ADDLTx) has been reported.

A randomized, multicenter study comparing steroid-free immunosuppression and standard immunosuppression for liver transplant recipients with chronic hepatitis C

This randomized, prospective, multicenter trial compared the safety and efficacy of steroid‐free immunosuppression (IS) to the safety and efficacy of 2 standard IS regimens in patients undergoing transplantation for hepatitis C virus (HCV) infection. The outcome measures were acute cellular rejection (ACR), severe HCV recurrence, and survival. The patients were randomized (1:1:2) to tacrolimus (TAC) and corticosteroids (arm 1; n = 77), mycophenolate mofetil (MMF), TAC, and corticosteroids (arm 2; n = 72), or MMF, TAC, and daclizumab induction with no corticosteroids (arm 3; n = 146). In all, 295 HCV RNA–positive subjects were enrolled. At 2 years, there were no differences in ACR, HCV recurrence (biochemical evidence), patient survival, or graft survival rates. The side effects of IS did not differ, although there was a trend toward less diabetes in the steroid‐free group. Liver biopsy samples revealed no significant differences in the proportions of patients in arms 1, 2, and 3 with advanced HCV recurrence (ie, an inflammation grade ≥ 3 and/or a fibrosis stage ≥ 2) in years 1 (48.2%, 50.4%, and 43.0%, respectively) and 2 (69.5%, 75.9%, and 68.1%, respectively). Although we have found that steroid‐free IS is safe and effective for liver transplant recipients with chronic HCV, steroid sparing has no clear advantage in comparison with traditional IS. Liver Transpl, 2011.

A prospective randomized trial of mycophenolate mofetil with neoral or tacrolimus after orthotopic liver transplantation

BACKGROUND The success of liver transplantation in this decade has become the stimulus to extend the donor and recipient pool. Reducing early posttransplant morbidity to maintain our success, as we expand our frontiers, has led us to focus on balanced testing of multidrug immunosuppression regimens. METHODS A prospective trial in orthotopic liver transplantation using Mycophenolate Mofetil and an identical steroid taper with randomization of patients to Neoral (N) or Tacrolimus (FK) is the basis of this report. This was an intent-to-treat study designed to compare the 6-month primary endpoints of rejection and infection and to compare the 6-month secondary endpoints of liver function, renal function, bone marrow function, hypertension, and serum cholesterol levels. RESULTS Ninety-seven patients completed the 6-month follow-up period (N=49, FK=48). The actual 6-month patient and graft survival rates were 98% and 94%, respectively. There was no difference in the number of patients with rejection episodes (N=11, FK=8) (P=0.61). There were 24 infections (3 cytomegalovirus) in the FK group and 30 infections (9 cytomegalovirus) in the N group. The cholesterol levels at 6 months were not significantly different (P=0.07) between the groups. The other secondary 6-month endpoints were not significantly different, except total bilirubin, which was lower in the FK arm (P=0.02). CONCLUSIONS The use of Mycophenolate Mofetil with N or FK and an identical steroid taper after orthotopic liver transplantation is associated with excellent graft and patient survival, and at 6 months, only 191% of the patients experienced rejection, with a 48% overall infection rate.