Marc P. Posner

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.

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.

Effects of interferon treatment on liver histology and allograft rejection in patients with recurrent hepatitis C following liver transplantation

Recurrent hepatitis C after liver transplantation remains a significant cause of graft loss and retransplantation. Although treatment of recurrent hepatitis C with interferon‐based regimens has become widely accepted as safe and can lead to sustained virologic clearance of hepatitis C virus (HCV) RNA, long‐term histologic improvement and the risk of precipitating graft rejection remain controversial. The present study is a retrospective evaluation of the clinical and histological consequences of treating recurrent hepatitis C with interferon‐based therapy in a selected group of liver transplant recipients. Twenty‐three liver transplant recipients with recurrent hepatitis C and histologic evidence of progressive fibrosis completed at least 6 months of interferon, 83% of whom received pegylated‐interferon α‐2b; only 4 tolerated ribavirin. Overall, 11 patients (48%) had undetectable HCV RNA at the end of 6 months of treatment. Of these patients, 3 remained HCV RNA–negative on maintenance interferon monotherapy for 33 months, and the other 8 (35%) completed treatment and remained HCV RNA–undetectable 24 weeks after discontinuation of interferon. Overall necroinflammatory activity in liver biopsies obtained 2 years after HCV RNA became undetectable decreased significantly (7.73 ± 2.37 vs. 5.64 ± 2.94 units before and after treatment, respectively; P = .016). However, 5 of these 11 patients had no histologic improvement in follow‐up liver histology. Liver biopsies in the 12 nonresponders demonstrated disease progression. Of the 23 patients treated with interferon, 8 (35%) had evidence of acute or chronic rejection on posttreatment liver biopsy, most of whom had no previous history of rejection (P < .01 for comparison of pretreatment and posttreatment prevalence of histologic rejection), and 2 experienced graft loss from chronic rejection, requiring retransplantation. In conclusion, interferon treatment of recurrent hepatitis C does not consistently improve histologic disease after virologic response, and it may increase the risk of allograft rejection. (Liver Transpl 2004;10:850–858.)

Histologic recurrence of chronic hepatitis C virus in patients after living donor and deceased donor liver transplantation

Hepatitis C virus (HCV) recurs in nearly all patients after liver transplantation. This recurrence is associated with progressive fibrosis and graft loss. It remains unclear whether the natural course of HCV recurrence is altered in patients who undergo living donor liver transplantation (LDLT). We conducted a prospective, controlled trial using protocol liver biopsies to evaluate the histologic outcome of recurrent HCV in 23 patients who underwent LDLT and 53 patients who underwent transplantation with a deceased donor liver (DDLT) during the same period of time. Patients who did not survive at least 6 months after transplantation or who had hepatocellular carcinoma or any other coexistent liver disease were excluded from analysis. All patients underwent protocol liver biopsy at 6 months and at 12 months and at yearly intervals thereafter. The mean age, sex, racial distribution, and serum HCV RNA and the percentage of patients with genotype 1 were similar in the 2 groups of patients. The model for end‐stage liver disease score at the time of transplantation was slightly lower in patients who underwent LDLT, but this difference was not significant. The distribution of immunosuppression agents used, the mean doses of calcineurin agents, the use of mycophenolate mofetil, and the dose and tapering schedule for prednisone were similar in both groups of patients. The mean duration of follow‐up was 40 months. No significant difference in either graft or patient survival or the percentage of patients who developed acute rejection was noted in the 2 groups of patients. At 48 months, graft and patient survival were 82% and 82% and 75% and 79% for patients who underwent DDLT and LDLT, respectively. The degree of hepatic inflammation increased stepwise over 3 years but was not significantly different in the 2 patient groups. In contrast, the mean fibrosis score and the percentage of patients with fibrosis increased stepwise after DDLT but appeared to plateau 12 months after LDLT. At 36 months, fibrosis was present in 78% of DDLT patients, and mean fibrosis score was 1.9, compared with 59% with fibrosis and a mean score of .9 after LDLT. In conclusion, these data strongly suggest that fibrosis progression from recurrent HCV is not more severe in patients after LDLT. (Liver Transpl 2004;10:1248–1255.)

A prospective evaluation of fibrosis progression in patients with recurrent hepatitis C virus following liver transplantation

Recurrence of hepatitis C virus (HCV) following liver transplantation (LT) is universal. A subset of these patients develop advanced fibrosis and cirrhosis and it is believed that this leads to increased posttransplantation mortality. The specific aims of this study were to determine the incidence of advanced fibrosis and those factors associated with this process, and to evaluate causes for mortality in patients with recurrent HCV. A total of 227 patients who underwent LT with chronic HCV were monitored prospectively. The mean age of this group at LT was 49.5 yr; 76% were male and 85% were Caucasian. Fibrosis progression was monitored by protocol liver biopsy, initially performed 6 months after LT and then at 6‐ to 24‐month intervals. Advanced fibrosis, defined as the bridging fibrosis or cirrhosis, developed in 1%, 11%, 25%, and 41% of patients after 1, 3, 5, and 6‐10 yr, respectively. Acute cellular rejection hepatic steatosis, a persistent elevation in serum alanine aminotransferase and donor‐race were associated with the development of advanced fibrosis. In contrast, the development of advanced fibrosis was not affected by the use of interferon prior to undergoing LT, cytomegalovirus disease, or donor age. A total of 60 patients (26%) died over 15 yr of follow‐up. Although graft failure accounted for 45% of deaths in patients with advanced fibrosis, this represented only 8% of all deaths in patients with recurrent HCV. Sepsis was the most common cause of death and this was observed with similar frequency in patients who developed advanced fibrosis (45%) and in those with less advanced fibrosis (47%). In conclusion, approximately 41% of patients with recurrent HCV developed advanced fibrosis 6‐10 yr after LT. However, complications associated with sepsis, not recurrent cirrhosis, was the most common cause of death in patients with recurrent HCV and this was similar in patients with or without advanced fibrosis. Liver Transpl 13:975–983, 2007.

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.

Surveillance for Hepatocellular Carcinoma in Patients with Cirrhosis Improves Outcome

OBJECTIVE Liver transplantation has become an effective treatment for cirrhotic patients with early-stage hepatocellular carcinoma. We hypothesized that the quality of surveillance for hepatocellular carcinoma influences prognosis by affecting access to liver transplantation. METHODS A total of 269 patients with cirrhosis and hepatocellular carcinoma were retrospectively categorized into 3 groups according to quality of surveillance: standard-of-care (n=172) (group 1); substandard surveillance (n=48) (group 2); and absence of surveillance in patients not recognized to be cirrhotic (n=59) (group 3). RESULTS Three-year survival in the 60 patients who underwent liver transplantation was 81% versus 12% for patients who did not undergo transplantation (P<.001). The percentages of patients who underwent transplantation according to tumor stage at diagnosis (T1, T2, T3, and T4) were 58%, 35%, 10%, and 1%, respectively. Hepatocellular carcinoma was diagnosed at stages 1 and 2 in 70% of patients in group 1, 37% of patients in group 2, and only 18% of patients in group 3 (P <.001). Liver transplantation was performed in 32% of patients in group 1, 13% of patients in group 2, and 7% of patients in group 3 (P<.001). Three-year survival from cancer diagnosis in patients in group 3 (12%) was significantly worse than in patients in group 1 (39%) or group 2 (27%) (each P<.05). Eighty percent of patients in group 3 had subtle abnormalities of cirrhosis on routine laboratory tests. CONCLUSION The quality of surveillance has a direct impact on hepatocellular carcinoma stage at diagnosis, access to liver transplantation, and survival.

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.