Emergency orthotopic liver transplantation (OLT) is currently the only standard treatment for fulminant hepatic failure (FHF). The waiting time for transplantation can exceed a week-using a liver assist device to bridge patients with FHF to OLT might therefore decrease the mortality rate. Several liver support systems have been described, but no system has gained FDA approval or widespread clinical acceptance. Although the results of many experimental and clinical trials are encouraging, the field is still in its initial stages. Using nonbiologic liver support is based on the assumption that several toxins that cause hepatic coma can be removed from the circulation by blood or plasma sorption methods. As these toxins could be involved in many FHF complications recovery without the need for transplantation is the ultimate aim. Biologic liver support uses xenogeneic livers or hepatocytes to support the failed human liver, exploiting biological cell functions, namely detoxification, metabolism, and biosynthesis. The classical nonbiologic dialysis methods could decrease mortality in patients with acute-on-chronic liver failure, but definitive conclusions are impossible to draw because of the small number of patients studied and inadequate follow-up. Larger studies performed in specialty centers should provide conclusive data about the role of the bioartificial liver support system as a possible universal bridge to OLT. This article presents an overview of published experience with liver support systems since the 1960s.

Humans↗

PubMed2005

Transjugular intrahepatic portosystemic shunt placement in liver transplant recipients: experiences with pediatric and adult patients.

OBJECTIVE: The purpose of our study was to evaluate the safety and efficacy of transjugular intrahepatic portosystemic shunts (TIPS) in pediatric and adult liver transplant recipients. A retrospective review of six TIPS placed in six liver transplant recipients-a pediatric patient with a split liver transplant, a pediatric patient with left lateral segment transplant, and four adult patients-was performed. CONCLUSION: TIPS placement in both pediatric and adult liver transplant recipients is feasible. In liver transplant patients who are recipients of a left lateral segment or a split liver transplant, knowledge of the liver transplant anatomy is critical in the placement of TIPS. TIPS placement is a treatment option and a bridge to retransplantation for patients who have undergone liver transplantation and develop sequelae of portal hypertension.

Adolescent↗

PubMed2004

Prospective, randomized trial of the effect of antibody induction in simultaneous pancreas and kidney transplantation: three-year results.

BACKGROUND: Historically, antibody induction has been used because of the higher immunologic risk of graft loss or rejection observed in simultaneous pancreas and kidney (SPK) transplantation compared with kidney transplantation alone. This trial was designed to assess the effect of antibody induction in SPK transplant recipients receiving tacrolimus, mycophenolate mofetil, and corticosteroids. Induction agents included T-cell-depleting and interleukin-2 receptor antibodies. METHODS: A total of 174 SPK transplant recipients were enrolled in a prospective, open-label, multi-center study. They were randomized to induction (n=87) or non-induction (n=87) groups and followed for 3 years. RESULTS: At 3 years, actual patient (94.3% and 89.7%) and pancreas (75.9% and 75.9%) survivals were similar between the induction and non-induction groups, respectively. Actual kidney survival was similar at 1 and 2 years, but at 3 years, it was significantly better in the induction group compared with the non-induction group (92% vs. 81.6%; P =0.04). At 3 years, median serum creatinine and hemoglobin A1C were similar between the induction and non-induction groups (1.35 mg/dL and 1.20 mg/dL, 5.4% and 5.5%, respectively). Three-year cumulative incidence of biopsy-confirmed, treated acute kidney rejection in the induction and non-induction groups was 19.5% and 27.5% (P =0.14), respectively, with odds 4.6 times greater in African Americans regardless of treatment (P =0.004). Significantly higher rates of cytomegalovirus (CMV) viremia and CMV syndrome occurred in those receiving T-cell-depleting antibody induction (36.1%) when compared with those receiving anti-interleukin-2 receptor antibodies (2%) and non-induction (8.1%) (P <0.0001). CONCLUSIONS: Tacrolimus, mycophenolate mofetil, and corticosteroids resulted in excellent safety and efficacy in SPK transplant recipients. Actual 3-year kidney survival was significantly better in the induction group; however, CMV viremia and CMV syndrome rates were significantly higher in the T-cell-depleting antibody group. African Americans demonstrated a significantly greater risk of acute rejection despite antibody induction. Decisions regarding the use of induction therapy must weigh the risk of kidney graft loss or rejection against the risk of infection.

Antibodies, Monoclonal↗

PubMed2004

Revisiting an old nemesis.

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Adult↗

PubMed2004

Summary report of a national conference: Evolving concepts in liver allocation in the MELD and PELD era. December 8, 2003, Washington, DC, USA.

A national conference was held to review and assess data gathered since implementation of MELD and PELD and determine future directions. The objectives of the conference were to review the current system of liver allocation with a critical analysis of its strengths and weaknesses. Conference participants used an evidence-based approach to consider whether predicted outcome after transplantation should influence allocation, to discuss the concept of minimal listing score, to revisit current and potential expansion of exception criteria, and to determine whether specific scores should be used for automatic removal of patients on the waiting list. After review of data from the first 18 months since implementation, association and society leaders, and surgeons and hepatologists with wide regional representation were invited to participate in small group discussions focusing on each of the main objectives. At the completion of the meeting, there was agreement that MELD has had a successful initial implementation, meeting the goal of providing a system of allocation that emphasizes the urgency of the candidate while diminishing the reliance on waiting time, and that it has proven to be a powerful tool for auditing the liver allocation system. It was also agreed that the data regarding the accuracy of PELD as a predictor of pretransplant mortality were less conclusive and that PELD should be considered in isolation. Recommendations for the transplant community, based on the analysis of the MELD data, were discussed and are presented in the summary document.

Adult↗

PubMed2004

Split-liver transplantation: coming of age.

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Journal Article↗

PubMed2003

The sickest first? Disparities with model for end-stage liver disease-based organ allocation: one region's experience.

February 27, 2002, allocation of cadaver livers for transplantation changed from a waiting-time-based system to an evidence-based system referred to as the Model for End-Stage Liver Disease (MELD). We reviewed data from 1 of the 11 United Network for Organ Sharing regions to determine the impact of the MELD on the allocation of cadaver livers for transplantation in that region. The region of interest (study region) consists of three distinct geographic areas (referred to as Transplant Service Areas [TSAs]). Based on information obtained from the Organ Procurement and Transplantation Network for the United States and for the study region, the following observations were made: (1) study region patients who received a cadaver liver had higher mean and median MELD scores than cadaver liver recipients in the United States (study region mean score, 25.1; median, 26.0; US mean score, 23.9; median, 24.0); (2) within the study region, TSAs with competing liver transplant programs performed transplantation on patients at a significantly higher mean MELD score than TSAs dominated by a single center (TSA-1 mean score, 27.3; TSA-2 mean score, 26.6; TSA-3 mean score, 21.3); this disparity persisted when transplantations for hepatocellular carcinoma (HCC) were excluded; and (3) study region patients removed from the waiting list because of death or being too sick for transplantation have higher MELD scores than the national average (study region mean score, 25.4; US mean score, 23.8). Overall, implementation of the MELD resulted in a substantial increase in the number of transplantations performed for HCC, and MELD exceptions for all reasons were more common in TSAs that have multiple centers. Despite the MELD, there remains disparity in organ allocation within the study region. The MELD may accurately predict pretransplantation mortality, but it does not ensure equitable organ distribution. We propose that intraregional sharing of cadaver livers based on the MELD may help limit disparities in organ allocation.

Adult↗

PubMed2003

Advances in adult living donor liver transplantation.

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Adult↗

PubMed2002

Initial experience with the modified extracorporeal liver-assist device for patients with fulminant hepatic failure: system modifications and clinical impact.

BACKGROUND: The need to find a safe, effective liver support system for patients with fulminant hepatic failure (FHF) continues to be unmet. A system using immortalized human hepatocytes was originally developed in the early 1990s. A modified version of the initial extracorporeal liver-assist device (ELAD) was recently placed into an initial clinical trial at the University of Chicago. The goal of this study was to determine the safety profile of the device at one center before broadening the study to other sites. METHODS: Patients who were diagnosed with FHF and admitted to the University of Chicago were eligible for the ELAD study. Informed consent was obtained, and patients received continuous ELAD therapy until and throughout transplantation. Data were prospectively collected and subsequently analyzed. RESULTS: Five patients were treated with the device. All patients successfully underwent transplantation. Four of the five patients survived to the 30-day endpoint of the study. There were no biomechanical problems identified. The patients' hemodynamic conditions did not deteriorate during treatment. The adult patients' clinical courses appeared to stabilize while connected to the ELAD (mean arterial pressure range 80-97, mean 88.6; cerebral perfusion pressure range 62-88, mean 76.5). Patient 4 experienced remarkable improvement during ELAD therapy: elimination of phenylephrine, reduction of dopamine from 20 microg/min to 5 microg/min, and reduction of respiratory support from 100% O2, 10 cm positive end-expiratory pressure to 60% O2, and 5 cm H2O positive end-expiratory pressure. The device continued to be metabolically active throughout the study period as documented by oxygen use (mean O2 change from sampling port before cartridge to sampling port after cartridge for all patients treated = 55 mm Hg). CONCLUSIONS: The patients tolerated treatment with the ELAD well. There were no unanticipated safety issues. The cells in the cartridges were metabolically active. All patients successfully underwent transplantation. The results from this single-institution experience indicates that larger randomized multicenter trials should proceed.

Adult↗

PubMed2002

Advances in pediatric liver transplantation: continuous monitoring of portal venous and hepatic artery flow with an implantable Doppler probe.

BACKGROUND: Acute vascular thrombosis is a dreaded complication in solid organ transplantation. Pediatric liver transplantation is associated with a high incidence of hepatic artery thrombosis. Graft salvage is dependent upon early recognition and correction of the thrombosis. Current methods of surveillance for vascular thrombosis lack early detection. METHODS: Four consecutive pediatric liver transplantations were performed using the implantable Doppler probe to monitor the patency of the hepatic artery and the portal vein during the early postoperative period. RESULTS: The implantable Doppler probes provided reliable monitoring of vascular patency. Early detection of hepatic artery thrombosis, with subsequent correction and graft salvage, was achieved with the use of the implantable Doppler probe. CONCLUSIONS: The implantable Doppler probe provides real-time surveillance of vascular patency for up to 7 days in the postoperative period. Signal quality and character was easily assessed by physician and nursing staff and reliably reflected intravascular flow.

Adolescent↗