Split liver transplantation.

Seventy-five thousand Americans develop organ failure each year. Fifteen percent of those on the list for transplantation die while waiting. Several possible mechanisms to expand the organ pool are being pursued including the use of extended criteria donors, living donation, and split deceased donor transplants. Cadaveric organ splitting results from improved understanding of the surgical anatomy of the liver derived from Couinaud. Early efforts focused on reduced-liver transplantation (RLT) reported by both Bismuth and Broelsch in the mid-1980s. These techniques were soon modified to create both a left lateral segment graft appropriate for a pediatric recipient and a right trisegment for an appropriately sized adult. Techniques of split liver transplantation (SLT) were also modified to create living donor liver transplantation. Pichlmayr and Bismuth reported successful split liver transplantation in 1989 and Emond reported a larger series of nine split procedures in 1990. Broelsch and Busuttil described a technical modification in which the split was performed in situ at the donor institution with surgical division completed in the heart beating cadaveric donor. In situ splitting reduces cold ischemia, simplifies identification of biliary and vascular structures, and reduces reperfusion hemorrhage. However, in situ splits require specialized skills, prolonged operating room time, and increased logistical coordination at the donor institution. At UCLA over 120 in situ splits have been performed and this technique is the default when an optimal donor is available. Split liver transplantation now accounts for 10% of adult transplantations at UCLA and 40% of pediatric transplantations.

Correlation between donor age and the pattern of liver graft recovery after transplantation.

We have observed an increased rate of delayed nonfunction (DNF) of liver grafts procured from older donors. The aim of this study was to correlate donor age and the patterns of graft failure after transplantation. Pattern of liver injury, synthetic function, and graft survival in recipients receiving liver grafts from donor older than age 50 (group I, n = 95) were compared with matched cohort of recipients transplanted with grafts from donors age 20-30 (group III, n = 50). Primary nonfunction (PNF) of the graft was defined as non-recoverable hepatocellular function necessitating emergency retransplantation within 72 hr. DNF was defined as marginal graft function necessitating retransplantation within one month. Recipient characteristics, including age and preoperative UNOS status, were similar between groups. Ischemic/reperfusion injury, reflected by SGOT and SGPT was more severe in older donors. PNF occurred at similar frequencies for all groups (7%). Normal liver function was regained in 76% of recipients in group I, and in 92% in group II. However, cholestatic pattern was observed in recipient of grafts from group I donors. Rapid rise in bilirubin, despite normalization of prothrombin time and liver transaminases, was the hallmark of DNF. DNF resulted in higher retransplantation rate in group I (24% vs. 8% in group II). Donor age did not affect patient survival. Liberalizing criteria for donor selection, and acceptance of older donors is a calculated risk. Over 75% of the recipients will regain normal liver function. However, a higher number of these grafts will exhibit slow recovery after transplantation, and a significant rate of DNF. Recognition of such pattern and early retransplantation should decrease mortality.

Rapid en bloc technique for pancreas-liver procurement. Improved early liver function.

It is our experience that warm dissection in the porta hepatis as well as extensive organ mobilization during combined pancreas-liver procurements may cause posttransplant dysfunction of the liver. To avoid this, we recently utilized a rapid en bloc procurement technique with minimal warm dissection and division of the liver and pancreas ex vivo. Fifteen procurements were performed using this rapid en bloc technique; seventeen procurements involved extensive dissection followed by sequential in situ procurement of the liver and pancreas grafts. The control group consisted of 15 age-matched patients who received livers when no pancreas was harvested. Dissection time was 157 +/- 13 min (mean +/- SEM) in the in situ group, 78 +/- 3 min in the en bloc group (P<0.02), and 51 +/- 6 min in the liver only group (P<0.02). There was no difference in donor age, cold ischemia time, or recipient United Network for Organ Sharing status. Pancreata obtained using the en bloc technique all had immediate function and there were no episodes of acute pancreatitis. Early liver graft function, as assessed by lactate dehydrogenase, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, and total bilirubin levels, was significantly lower in the en bloc and liver only group when compared with the in situ group. The total hospital stay was also significantly lower in these groups. We conclude that the rapid en bloc technique decreases operative time during the donor operation. Procurement-related injury to the liver graft is minimized without compromising pancreas graft function.

Liver transplantation for decompensated cirrhosis after jejunoileal bypass: a strategy for management.

BACKGROUND: Although jejunoileal bypass results in end-stage liver disease in up to 100% of patients, little is known about outcome after liver transplantation. METHODS: The clinical courses of six patients who underwent liver transplantation at UCLA for decompensated cirrhosis owing to a jejunoileal bypass were reviewed. Liver function, allograft pathology, renal function, and nutritional status were assessed. RESULTS: Of the four patients with an intact jejunoileal bypass, two of the three who were biopsied had recurrent steatotic liver disease. The two patients whose jejunoileal bypass was reversed at the time of liver transplantation had lower alkaline phosphatase, lower creatinine, higher albumin, and higher cholesterol, and were more obese than their counterparts with intact bypasses. CONCLUSIONS: Patients undergoing liver transplantation for jejunoileal bypass-associated liver disease should, if possible, have their bypass reversed at the time of transplantation; otherwise, they must be followed closely and be biopsied routinely. Recurrent liver disease should prompt reversal of the jejunoileal bypass.

Preoperative factors associated with outcome and their impact on resource use in 1148 consecutive primary liver transplants.

BACKGROUND: Hepatic transplantation is a highly effective but costly treatment for end-stage hepatic dysfunction. One approach to improve efficiency in the use of scarce organs for transplantation is to identify preoperative factors that are associated with poor outcome posttransplantation. This may assist both in selecting patients optimal for transplantation and in identifying strategies to improve survival. METHODS: In the present work, we retrospectively reviewed consecutive liver transplants performed at the University of California at Los Angeles during a 6-year period and determined preoperative variables that were associated with outcome in primary grafts. In addition, we used the hospital's cost accounting database to determine the impact of these variables on the degree of resource use by high-risk patients. RESULTS: We found five variables to have independent prognostic value in predicting graft survival after primary liver transplantation: (1) donor age, (2) recipient age, (3) donor sodium, (4) recipient creatinine, and (5) recipient ventilator requirement pretransplant. Recipient ventilator requirement and elevated creatinine were associated with significant increases in resource use during the transplant admission. CONCLUSIONS: Patients at high risk for graft failure and costly transplants can be identified preoperatively by a set of parameters that are readily available, noninvasive, and inexpensive. Selection of recipients on the basis of these data would improve the efficiency of liver transplantation and reduce its cost.

Early graft function after pediatric liver transplantation: comparison between in situ split liver grafts and living-related liver grafts.

BACKGROUND: The systematic application of living-related and cadaveric, in situ split-liver transplantation has helped to alleviate the critical shortage of suitable-sized, pediatric donors. Undoubtedly, both techniques are beneficial and advantageous; however, the superiority of either graft source has not been demonstrated directly. Because of the potential living-donor risks, we reserve the living donor as the last graft option for pediatric recipients awaiting liver transplantation. Inasmuch as no direct comparison between these two graft types has been performed, we sought to perform a comparative analysis of the functional outcomes of left lateral segmental grafts procured from these donor sources to determine whether differences do exist. METHODS: A retrospective analysis of all liver transplants performed at a single institution between February 1984 and January 1999 was undertaken. Only pediatric (<18 years) recipients of left lateral segmental grafts procured from either living-related (LRD) or cadaveric, in situ split-liver (SLD) donors were included. A detailed analysis of preoperative, intraoperative, and postoperative variables was undertaken. Survival was estimated using the Kaplan-Meier method, and comparison of variables between groups was undertaken using the t test of Wilcoxon rank sum test. RESULTS: There were no significant differences in the preoperative variables between the 39 recipients of SLD grafts and 34 recipients of LRD grafts. The donors did differ significantly in mean age, ABO blood group matching, and preoperative liver function testing. Postoperative liver function testing revealed significant early differences in aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, prothrombin time, and alkaline phosphatase, with grafts from LRD performing better than those from SLD. SLD grafts also had significantly longer ischemia times and a higher incidence of graft loss owing to primary nonfunction and technical complications (9 vs. 2, P<0.05). However, six of these graft losses in the SLD group were because of technical or immunologic causes, which, theoretically, should not differ between the two groups. Furthermore, these graft losses did not negatively impact early patient survival as most patients were successfully rescued with retransplantation (30-day actuarial survival, 97.1% SLD vs. 94.1% LRD, P=0.745). In the surviving grafts, the early differences in liver function variables normalized. CONCLUSIONS: Inherent differences in both donor sources exist and account for differences seen in preoperative and intraoperative variables. Segmental grafts from LRD clearly performed better in the first week after transplantation as demonstrated by lower liver function variables and less graft loss to primary nonfunction. However, the intermediate function (7-30 days) of both grafts did not differ, and the early graft losses did not translate into patient death. Although minimal living-donor morbidity was seen in this series, the use of this donor type still carries a finite risk. We therefore will continue to use SLD as the primary graft source for pediatric patients awaiting liver transplantation.

Randomized controlled trial to evaluate flush and reperfusion techniques in liver transplantation.

To determine the impact of different flush and reperfusion techniques on postreperfusion syndrome (PRS) and postoperative graft function, 100 transplants were randomly assigned into four groups as follows: group 1 (n=31), portal vein flush, no vena caval venting; group 2 (n=21), hepatic arterial flush, no vena caval venting; group 3 (n=29), portal vein flush with vena caval venting; and group 4 (n=19), hepatic artery flush with vena caval venting. Donor and recipient characteristics were similar. Extensive intraoperative and postoperative monitoring was performed and measurements were documented immediately before reperfusion and at 1, 5, 15, and 30 min after reperfusion. PRS was defined by three criteria: mean arterial pressure (MAP) <60 mmHg at 1 min after reperfusion, MAP <60 mmHg at 5 min after reperfusion, and a decrease of 30% or more for the MAP percent area under the curve during the initial 5 min after reperfusion (%AUC). Using these definitions, the overall incidence of PRS was 21%, 8%, and 43%, respectively. Group 1 was the most hemodynamically stable; the incidence of PRS in group 1 was 2/31 (7%) at 1 min and 8/31 (25%) using %AUC criteria compared with 7/21 (33%) at 1 min and 12/21 (57%) using %AUC criteria for group 2 (P<0.05). The patients in groups 3 and 4 (vena caval venting) demonstrated smaller percentage increases in serum potassium levels (as determined by %AUC; 4.3+/-6.8 and 0.3+/-5.4, vs. 15.1+/-8.1 for group 1 and 22.9+/-8.2 for group 2). The difference between group 4 and group 2 was statistically significant (P<0.05). The increases in serum potassium did not translate into increased cardiac or hemodynamic instability. Combining all data obtained over the first 30 min after reperfusion, there was no statistically significant difference in hemodynamic or biochemical changes noted among the four groups. Postoperative liver function was similar among the four groups. We conclude that portal vein flush without vena caval venting provided a lower incidence of PRS than any other technique. Vena caval venting decreased the release of potassium into the circulation. Postoperative graft function was not significantly affected by flush and reperfusion techniques.

In situ splitting of the cadaveric liver for transplantation.

BACKGROUND: The shortage of cadaveric donor livers is the rate-limiting step in clinical liver transplantation. Split liver transplantation provides a means to expand the cadaveric donor pool. However, this concept has not reached its full potential because of inferior patient and graft survival and high complication rates when traditional ex vivo split techniques are used. Therefore we sought to evaluate the safety, applicability, and effectiveness of a new technique for split liver transplantation. METHODS: This study consists of 15 in situ split liver procurements, which resulted in 28 liver transplants. In situ splitting of selected livers from hemodynamically stable cadaveric donors was performed at the donor hospital without any additional work-up or equipment being needed. In situ liver splitting is accomplished in a manner identical to the living-donor procurement. This technique for liver splitting results in a left lateral segment graft (segments 2 and 3) and a right trisegmental graft (segments 1 and 4-8). This procedure required the use of the donor hospital operating room for an additional 1.5-2.5 hr and did not interfere with the procurement of 30 kidneys, 12 hearts, 7 lungs, and 9 pancreata from these same donors. RESULTS: The 6-month and 1-year actuarial patient survival rates were 92% and 92%, respectively, while the 6-month and 1-year actuarial graft survival rates were 86% and 86%, respectively. The 6-month and 1-year actuarial patient survival rate of patients who received a left lateral segment graft was 100% and 100%, respectively, while those who received a right trisegmental graft had 6-month and 1-year rates of 86% and 86%, respectively. The actuarial death-censored graft survival rates at 6 months and 1 year were 80% and 80%, respectively, for the left lateral segment grafts, and 93% and 93%, respectively, for the right trisegmental grafts. Alograft and patient survival was independent of United Network for Organ Sharing status at the time of liver transplantation. No patient developed a biliary stricture, required re-exploration for intra-abdominal hemorrhage, or suffered from portal vein, hepatic vein, or hepatic artery thrombosis CONCLUSIONS: In situ split liver transplantation can be accomplished without complications and provides results that are superior to those obtained previously with ex vivo methods. It abolishes ex vivo benching and prolonged ischemia times and provides two optimal grafts with hemostasis accomplished. This technique decreases pediatric waiting time and allows adult recipients to receive right-sided grafts safely. In situ splitting is the method of choice for expanding the cadaveric liver donor pool.

A simple model to estimate survival after retransplantation of the liver.

To formulate a model predicting survival after liver retransplantation, we analyzed in detail the last 150 cases of hepatic retransplantation at UCLA. Cox proportional hazards regression analysis identified five variables that demonstrated independent simultaneous prognostic value in estimating patient survival after retransplantation: (1) age group (pediatric or adult), (2) recipient requiring preoperative mechanical ventilation, (3) donor organ cold ischemia > or =12 hr, (4) preoperative serum creatinine, and (5) preoperative serum total bilirubin. The Cox regression equation that predicts survival based on these covariates was simplified by assigning individual patients a risk classification based on a 5-point scoring system. We demonstrate that this system can be employed to identify a subgroup of patients in which the expected outcome is too poor to justify retransplantation. These findings may assist in the rational selection of patients suitable for retransplantation.

A prospective study on the reliability and cost effectiveness of preoperative ultrasound screening of the "marginal" liver donor.

With the growing shortage of available liver donors, many donors with risk factors that would have traditionally precluded liver procurement are now being considered. In this prospective study, we evaluated 50 "marginal" liver donors with pre-procurement abdominal ultrasounds and correlated results with findings at procurement and with subsequent allograft function. The results show that the ultrasounds have a specificity of 96% and a sensitivity of 68% in predicting abnormalities in donor livers that precluded transplantation. In addition, using ultrasound to screen marginal donors would result in significant savings in manpower and hospital resource utilization without "missing" any normal liver organs. Our results also show that, when properly selected, livers from donors with one or more high-risk factors function well with acceptable primary nonfunction rates.

Outcome after intestinal transplantation: results from one center's 9-year experience; discussion 1031-2.

HYPOTHESIS: Outcomes after intestinal transplantation have improved during the past decade with refinements in surgical techniques as well as advances in immunosuppression and antimicrobial therapy. DESIGN: Retrospective analysis. SETTING: Tertiary care medical center, August 1991 through December 2000. PATIENTS: Adult (5) and pediatric (12) patients with intestinal failure. All developed complications from long-term total parenteral nutrition therapy. Median age was 8.6 years and median weight was 22 kg. INTERVENTIONS: Primary intestinal transplantation with (n = 14) or without (n = 3) the liver. MAIN OUTCOME MEASURES: Patient and graft survival, viral infections, rejection, and nutritional autonomy. RESULTS: Twenty-one intestinal grafts were transplanted into the 17 recipients. All donors were cadaveric and were matched by ABO blood group and size. Patient survival at 1 and 3 years was 63% and 55%, respectively. Death-censored graft survival at 1 and 3 years was 73% and 55%, respectively. There were 1.5 acute cellular rejection episodes per graft and 3 grafts were lost to rejection. Incidences of infection with the Epstein-Barr virus and cytomegalovirus were negligible with aggressive prophylaxis and preemptive therapy. Nutritional autonomy was achieved in 69% of grafts surviving more than 30 days after intestinal transplantation. CONCLUSIONS: Intestinal transplantation is now the standard of therapy for patients with intestinal failure and complications resulting from total parenteral nutrition. Outcomes have markedly improved since initiation of the program. Aggressive immunosuppression as well as prophylaxis and preemptive antiviral therapy have led to low incidences of acute cellular rejection, Epstein-Barr virus, and cytomegalovirus. Finally, nutritional autonomy can be achieved after successful intestinal transplantation.

Application of combined liver-intestinal transplantation as a staged procedure.

Liver-intestinal transplantation is a complex surgical procedure that historically has required prolonged operative periods. This report is the first series where liver-intestinal transplantation was performed as a staged procedure. Specifically, allograft reperfusion was followed by resuscitation and stabilization in an intensive care unit before completion of the transplant procedure. Triage of recipients to the intensive care unit following allograft reperfusion was determined at the time of operation and was based upon the clinical condition of the recipient including hemodynamic stability, evidence of coagulopathy, and assessment of early liver function. Medical stabilization was followed by completion of the transplant procedure and definitive abdominal closure within 72 hours. The application of combined liver-intestinal transplantation as a staged procedure demonstrated no effect upon early graft function, incidence of complications, or ability to perform a definitive abdominal closure.

Induction therapy with interleukin-2 receptor antagonist after intestinal transplantation is associated with reduced acute cellular rejection and improved renal function.

PURPOSE: To determine the effectiveness of induction immunotherapy with interleukin-2 receptor antagonists (IL2RA) after intestinal transplantation (IT). METHODS: A single-center, retrospective study was undertaken of all patients undergoing IT using existing medical records and database. Immunotherapy was either triple (standard maintenance triple therapy [SMTT]) or IL2RA [induction IL2RA plus SMTTx] or OKT3 [induction antilymphocyte preparations plus SMTTx]). Data was collected for the first 175 postoperative days. Outcomes included pretransplant renal function, posttransplant serum creatinine normalized to age (nl-sCR), rejection (ACR), and survival. Standard statistical analysis was undertaken. RESULTS: There were no significant differences in the groups: triple (n = 10, median age 3.5 years, cGFR 106 +/- 44 mL/min), IL2RA (n = 13, median age 3.2 years, cGFR 101 +/- 61 mL/min), OKT3 (n = 4, median age 7.7 years, cGFR 104 +/- 27 mL/min). nl-sCR was significantly (P <.01) lower in IL2RA at most postoperative weeks. IL2RA had significantly fewer rejection and infectious episodes than the other two groups. Three-year patient survival was 92% in IL2RA versus 50% triple and OKT3. CONCLUSIONS: IL2RA immunotherapy after IT is associated with a lower incidence of renal dysfunction as compared with historical controls. Furthermore, IL2RA therapy resulted in a lower incidence of rejection and improved survival. IL2RA should be considered in select patients undergoing IT.

Improved outcome after intestinal transplantation at a single institution over 12 years.

PURPOSE: To evaluate the outcomes of patients undergoing intestinal transplantation (IT). METHODS: Retrospective review was undertaken using existing medical records and database. RESULTS: Between November 1991 and May 2003, 114 patients were referred for consideration for IT, of which 33 patients received 37 intestinal allografts. All patients had intestinal failure and all patients had significant complications from total parenteral nutrition (TPN). TPN was the predominant cause of liver failure (63%). Combined liver intestinal grafts were used in the majority of patients. Overall 1- and 3-year patient survival is 77% and 52% with patients transplanted since 1999 having a 1- and 3-year survival of 94% and 73%, respectively. The most common cause of death was sepsis. No graft or patient was lost to cytomegalovirus or Epstein-Barr virus disease. Twenty-seven percent of allografts were lost to rejection. Long-term TPN independence is 82% for grafts more than 30 days after IT. Statistical analysis revealed several important factors impacting outcome. CONCLUSIONS: Successful IT defined as prolonged patient and graft survival and TPN independence can be readily achieved in select patients with IF and complications related to TPN therapy. Outcomes have improved with experience gained and control of viral infections and rejection.