Conventional Liver Transplantation Research Articles

Development of a Large Animal Model of Ischemia-free Liver Transplantation in Pigs.

In organ transplantation, ischemia, and reperfusion injury (IRI) is considered as an inevitable event and the major contributor to graft failure. Ischemia-free liver transplantation (IFLT) is a novel transplant procedure that can prevent IRI and provide better transplant outcomes. However, a large animal model of IFLT has not been reported. Therefore, we develop a new, reproducible, and stable model of IFLT in pigs for investigating mechanisms of IFLT in IRI. Ten pigs were subjected to IFLT or conventional liver transplantation (CLT). Donor livers in IFLT underwent 6-h continuous normothermic machine perfusion (NMP) throughout graft procurement, preservation, and implantation, whereas livers in CLT were subjected to 6-h cold storage before implantation. The early reperfusion injury was compared between the 2 groups. Continuous bile production, low lactate, and liver enzyme levels were observed during NMP in IFLT. All animals survived after liver transplantation. The posttransplant graft function was improved with IFLT when compared with CLT. Minimal histologic changes, fewer apoptotic hepatocytes, less sinusoidal endothelial cell injury, and proinflammatory cytokine (interleukin [IL]-1β, IL-6, and tumor necrosis factor-α) release after graft revascularization were documented in the IFLT group versus the CLT group. We report that the concept of IFLT is achievable in pigs. This innovation provides a potential strategy to investigate the mechanisms of IRI and provide better transplant outcomes for clinical practice.

Substantial decline of organ preservation fluid contamination following adoption of ischemia-free liver transplantation: a post-hoc analysis.

Preservation fluid (PF) contaminations are common in conventional liver transplantation (CLT) and presumably originate from organ or PF exposures to the external environment in a non-strict sterile manner. Such exposures and PF contamination may be avoided in ischaemia-free liver transplantation (IFLT) because of the strict sterile surgical procedures. In this study, the authors evaluated the impact of IFLT on organ PF contamination. A post-hoc analysis using data from the first randomized controlled trial of IFLT was performed to compare the incidence, pathogenic spectrum of PF contamination, and incidence of early recipient infection between IFLT and CLT. Multivariable logistic regression was used to explore risk factors for PF contamination. Of the 68 cases recruited in the trial, 64 were included in this post-hoc analysis. The incidence of culture-positive PF was 9.4% (3/32) in the IFLT group versus 78.1% (25/32) in the CLT group ( P <0.001). Three microorganisms were isolated from PF in the IFLT group, while 43 were isolated in the CLT group. The recipient infection rate within postoperative day 14 was 3.1% (1/32) in the IFLT group vs 15.6% (5/32) in the CLT group, although this difference did not reach statistical significance ( P =0.196). Multivariate analysis revealed that adopting IFLT is an independent protective factor for culture-positive PF. PF contamination is substantially decreased in IFLT, and IFLT application is an independent protective factor for PF contamination. Using rigorous sterile measures and effective antibiotic therapy during IFLT may decrease PF contamination.

MMP inhibition as a novel strategy for extracellular matrix preservation during whole liver decellularization

As the only reliable treatment option for end-stage liver diseases, conventional liver transplantation confronts major supply limitations. Accordingly, the decellularization of discarded livers to produce bioscaffolds that support recellularization with progenitor/stem cells has emerged as a promising translational medicine approach. The success of this approach will substantially be determined by the extent of extracellular matrix (ECM) preservation during the decellularization process. Here, we assumed that the matrix metalloproteinase (MMP) inhibition could reduce the ECM damage during the whole liver decellularization of an animal model using a perfusion-based system. We demonstrated that the application of doxycycline as an MMP inhibitor led to significantly higher preservation of collagen, glycosaminoglycans, and hepatic growth factor (HGF) contents, as well as mechanical and structural features, including tensile strength, fiber integrity, and porosity. Notably, produced bioscaffolds were biocompatible and efficiently supported cell viability and proliferation in vitro. We also indicated that produced bioscaffolds efficiently supported HepG2 cell function upon seeding onto liver ECM discs using albumin and urea assay. Additionally, MMP inhibitor pretreated decellularized livers were more durable in contact with collagenase digestion compared to control bioscaffolds in vitro. Using zymography, we confirmed the underlying mechanism that results in these promising effects is through the inhibition of MMP2 and MMP9. Overall, we demonstrated a novel method based on MMP inhibition to ameliorate the ECM structure and composition preservation during liver decellularization as a critical step in fabricating transplantable bioengineered livers.

A randomized-controlled trial of ischemia-free liver transplantation for end-stage liver disease

Ischemia-reperfusion injury (IRI) has thus far been considered as an inevitable component of organ transplantation, compromising outcomes, and limiting organ availability. Ischemia-free organ transplantation is a novel approach designed to avoid IRI, with the potential to improve outcomes. In this randomized, controlled clinical trial, recipients of livers from donors after brain death were randomly assigned to receive either an ischemia-free or a 'conventional' transplant. Primary end point was the incidence of early allograft dysfunction. Secondary end points included complications related to graft IRI. 65 out of 68 randomized patients underwent transplants and were included in the analysis. 32 patients received ischemia-free liver transplantation (IFLT), and 33 received conventional liver transplantation (CLT). Early allograft dysfunction occurred in 2 (6%) randomized to IFLT and in 8 (24%) randomized to CLT (difference, -18%; 95% CI, -35% to -1%; P=.044). Post-reperfusion syndrome occurred in 3 (9%) randomized to IFLT and in 21 (64%) randomized to CLT (difference, -54%; 95% CI, -74% to -35%; P < .001). Non-anastomotic biliary strictures diagnosed with protocol magnetic resonance cholangiopancreatography at 12 months were observed in 2 recipients (8%) randomized to IFLT and in 9 recipients (36%) randomized to CLT (difference, -28%; 95% CI, -50% to -7%; P = .014). The comprehensive complication index at one year after transplantation was 30.48 (95% CI, 23.25-37.71) in the IFLT group vs 42.14 (95% CI, 35.01-49.26) in the CLT group (difference, -11.66; 95% CI, -21.81 to -1.51; P = .025). Among patients with end-stage liver disease, IFLT, compared with conventional approach, significantly reduced complications related to ischemia reperfusion injury. Chictr.org. ChiCTR1900021158 IMPACT AND IMPLICATIONS: Ischemia reperfusion injury has thus far been considered as an inevitable event in organ transplantation, compromising outcomes and limiting organ availability. Ischemia-free liver transplantation is a novel approach of transplanting donor livers without interruption of blood supply. We showed that in patients with end-stage liver disease, ischemia-free liver transplantation, compared with conventional approach led to reduced complications related to ischemia reperfusion injury in this randomized trial. This new approach is expected to change the current practice in organ transplantation improving transplant outcomes, increasing organ utilization, while providing a clinical model to delineate the impact of organ injury on alloimmunity.

Abrogation of graft ischemia-reperfusion injury in ischemia-free liver transplantation.

BackgroundIschemia‐reperfusion injury (IRI) is considered an inherent component of organ transplantation that compromises transplant outcomes and organ availability. The ischemia‐free liver transplantation (IFLT) procedure has been developed to avoid interruption of blood supply to liver grafts. It is unknown how IFLT might change the characteristics of graft IRI.MethodsSerum and liver biopsy samples were collected from IFLT and conventional liver transplantation (CLT) recipients. Pathological, metabolomics, transcriptomics, and proteomics analyses were performed to identify the characteristic changes in graft IRI in IFLT.ResultsPeak aspartate aminotransferase (539.59 ± 661.76 U/L versus 2622.28 ± 3291.57 U/L) and alanine aminotransferase (297.64 ± 549.50 U/L versus 1184.16 ± 1502.76 U/L) levels within the first 7 days and total bilirubin levels by day 7 (3.27 ± 2.82 mg/dl versus 8.33 ± 8.76 mg/dl) were lower in the IFLT versus CLT group (all p values < 0.001). The pathological characteristics of IRI were more obvious in CLT grafts. The antioxidant pentose phosphate pathway remained active throughout the procedure in IFLT grafts and was suppressed during preservation and overactivated postrevascularization in CLT grafts. Gene transcriptional reprogramming was almost absent during IFLT but was profound during CLT. Proteomics analysis showed that “metabolism of RNA” was the major differentially expressed process between the two groups. Several proinflammatory pathways were not activated post‐IFLT as they were post‐CLT. The activities of natural killer cells, macrophages, and neutrophils were lower in IFLT grafts than in CLT grafts. The serum levels of 14 cytokines were increased in CLT versus IFLT recipients.ConclusionsIFLT can largely avoid the biological consequences of graft IRI, thus has the potential to improve transplant outcome while increasing organ utilization.

Ischemic-Free Liver Transplantation Reduces the Recurrence of Hepatocellular Carcinoma After Liver Transplantation.

Ischemia reperfusion injury (IRI) is an adverse factor for hepatocellular carcinoma (HCC) recurrence after liver transplantation. Ischemic-free liver transplantation (IFLT) is a novel transplant procedure that can largely reduce or even prevent IRI, but the clinical relevance of IFLT and the recurrence of HCC after liver transplantation are still unknown. This retrospective study compared survival outcomes, HCC recurrence, perioperative data and IRI severity following liver transplantation (LT). 30 patients received IFLT and 196 patients received conventional liver transplantation (CLT) were chosen for the entire cohort between June 2017 and August 2020. A 1:3 propensity score matching was performed, 30 IFLT recipients and 85 matched CLT patients were enrolled in propensity-matched cohorts. An univariate and multivariate Cox regression analysis was performed, and showed surgical procedure (CLT vs IFLT) was an independent prognostic factor (HR 3.728, 95% CI 1.172-11.861, P=0.026) for recurrence free survival (RFS) in HCC patients following liver transplantation. In the Kaplan–Meier analysis, the RFS rates at 1 and 3 years after LT in recipients with HCC in the IFLT group were significantly higher than those in the CLT group both in the entire cohort and propensity-matched cohort (P=0.006 and P=0.048, respectively). In addition, patients in the IFLT group had a lower serum lactate level, lower serum ALT level and serum AST level on postoperative Day 1. LT recipients with HCC in the IFLT group had a lower incidence of early allograft dysfunction than LT recipients with HCC in the CLT group. Histological analysis showed no obvious hepatocyte necrosis or apoptosis in IFLT group. In conclusion, IFLT can significantly reduce IRI damage and has the potential to be a useful strategy to reduce HCC recurrence after liver transplantation.

Effects of a Domino Liver Transplantation Program on Patient Survival and Waiting List Time: A Single-Center Retrospective Study

Explanted livers from patients with familial amyloid polyneuropathy have often been used for domino liver transplantation (DLT). This has expanded the organ pool for liver transplantation. We evaluated the effects of a single-center DLT program on waiting list duration and patient survival. Liver transplants conducted from 2007 to 2017 were analyzed. Selected patients, all liver transplant candidates above the age of 60 years and patients with hepatocellular carcinoma, were offered DLT. Survival, time on waiting list, and operative factors were evaluated. The study group included 485 patients transplanted with grafts from deceased donors (conventional liver transplantation) and 149 patients who were offered and accepted a potential DLT, of whom 34 underwent DLT and 115 did not; these patients received a deceased donor graft (non-DLT). Five-year and overall estimated survival rates respectively were 79% and 54.4% for DLT and 67.6% and 46.7% for non-DLT (P=.67, log rank test). No differences were noted in survival (P=.816) or waiting times (P=1.0) between DLT and non-DLT groups. As expected, survival time in the conventional liver transplantation group was longer (84.7% and 60.6%, P < .001). Donor age and ischemia time were significantly different between DLT and non-DLT (P < .001). DLT has enabled 6% additional transplantations without affecting waiting time or survival (34/600).

Application of ischaemia‐free liver transplantation improves prognosis of patients with steatotic donor livers – a retrospective study

SummaryThe use of steatotic livers in liver transplantation (LT) is controversial. Ischaemia‐free liver transplantation (IFLT) has obvious advantages for the recovery of allograft function. The aim of this study was to examine the effect of liver grafts with steatosis on outcome and the effect of IFLT with steatotic livers. 360 patients with LT were enrolled in this study. Perioperative characteristics and differences in outcome among different grades of steatotic groups, and between the IFLT and conventional LT (CLT) groups were analysed. Occurrence of early allograft dysfunction (EAD; 50%) and primary nonfunction (PNF; 20%) was significantly higher in the severe steatosis group (P < 0.001 and <0.001, respectively). Survival rate is significantly low in severe steatosis group (3‐year: 60%, P = 0.0039). The IFLT group had a significantly lower occurrence of EAD than the CLT group (0% vs. 60%, P = 0.01). The level of postoperative peak AST, GGT and creatine were significantly lower in IFLT group (P = 0.009, 0.032 and 0.024, respectively). In multivariable analysis, IFLT and EAD were independent factors affecting postoperative survival. Severe steatotic livers lead to severe complications and poor outcomes in LT. IFLT has obvious advantages for reducing the rate of EAD in LT with steatotic livers.

Dextroplantation of Left Liver Graft in Infants.

The position of the left side liver graft is important, and it could lead to complications of the hepatic vein (HV) and portal vein (PV), especially in a small child using a variant left lateral section (vLLS) graft. The purpose of this study was to evaluate the outcome of a novel technique for the implantation of a vLLS graft to the right side (dextroplantation) in infants. For 3years, 10 consecutive infants underwent dextroplantation using a vLLS graft (group D). The graft was implanted to the right side of the recipient after 90° counterclockwise rotation; the left HV graft was anastomosed to inferior vena cava using the extended right and middle HV stump, and PV was reconstructed using oblique anastomosis without angulation. Surgical outcomes were compared with the historical control group (n=17, group C) who underwent conventional liver transplantation using a vLLS during infancy. Group D recipients were smaller than group C (body weight <6kg: 50.0% versus 11.8%; P=0.03). The rate of graft-to-recipient weight ratio >4% was higher in group D (60.0%) than C (11.8%; P=0.01). Surgical drains were removed earlier in group D than in group C (15 versus 18 postoperative days [PODs]; P=0.048). Each group had 1 PV complication (10.0% versus 5.9%); no HV complication occurred in group D, but 3 HV complications (17.6%) occurred in group C (P>0.05). Hospital stay was shorter in group D than in group C (20 versus 31 PODs; P=0.02). Dextroplantation of a vLLS graft, even a large-for-size one, was successful in small infants without compromising venous outcomes, compared with conventional vLLS transplantation. We could remove the surgical drains earlier and reduce hospital stays in cases of dextroplantation.

Regulated differentiation of stem cells into an artificial 3D liver as a transplantable source.

End-stage liver disease is one of the leading causes of death around the world. Since insufficient sources of transplantable liver and possible immune rejection severely hinder the wide application of conventional liver transplantation therapy, artificial three-dimensional (3D) liver culture and assembly from stem cells have become a new hope for patients with end-stage liver diseases, such as cirrhosis and liver cancer. However, the induced differentiation of single-layer or 3D-structured hepatocytes from stem cells cannot physiologically support essential liver functions due to the lack of formation of blood vessels, immune regulation, storage of vitamins, and other vital hepatic activities. Thus, there is emerging evidence showing that 3D organogenesis of artificial vascularized liver tissue from combined hepatic cell types derived from differentiated stem cells is practical for the treatment of end-stage liver diseases. The optimization of novel biomaterials, such as decellularized matrices and natural macromolecules, also strongly supports the organogenesis of 3D tissue with the desired complex structure. This review summarizes new research updates on novel differentiation protocols of stem cell-derived major hepatic cell types and the application of new supportive biomaterials. Future biological and clinical challenges of this concept are also discussed.

Evolving thresholds for liver transplantation in hepatocellular carcinoma: A Western experience.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer‐related deaths worldwide. Once considered an experimental treatment with dismal survival rates, liver transplantation for HCC entered a new era with the establishment of the Milan criteria over 20 years ago. In the modern post‐Milan‐criteria era, 5‐year survival outcomes are now upwards of 70% in select patients. Liver transplantation (LT) is now considered the optimal treatment for patients with moderate to severe cirrhosis and HCC, and the rates of transplantation in the United States are continuing to rise. Several expanded selection criteria have been proposed for determining which patients with HCC should be candidates for undergoing LT with similar overall and recurrence‐free survival rates to patients within the Milan criteria. There is also a growing experience with downstaging of patients who fall outside conventional LT criteria at the time of HCC diagnosis with the goal of tumor shrinkage via locoregional therapies to become a candidate for transplantation. The aim of this review article is to characterize the various patient selection criteria for LT, discuss balancing organ stewardship with outcome measures in HCC patients, present evidence on the role of downstaging for large tumors, and explore future directions of LT for HCC.

Is resectable hepatocellular carcinoma a contraindication to liver transplantation? A novel decision model based on “number of patients needed to transplant” as measure of transplant benefit

Number-needed-to-treat is used in assessing the effectiveness of a health-care intervention, and reports the number of patients who need to be treated to prevent one additional bad outcome. Although largely used in medical literature, there are no studies measuring the benefit of liver transplantation (LT) over hepatic resection (HR) for hepatocellular carcinoma (HCC) in terms of "Number of patients needed to transplant (NTT)." Child-Turcotte-Pugh (CTP) Classes B-C, very large (>10 cm) and multi-nodular (>2 nodules) tumours, macroscopic vascular invasion and extra-hepatic metastases. 1028 HCC cirrhotic patients from one Eastern (n=441) and two Western (n=587) surgical units. Patient survival observed after HR by proportional hazard regression model was compared to that predicted after LT by the Metroticket calculator. The benefit obtainable from LT compared to resection was analysed in relationship with number of nodules (modelled as ordinal variable: single vs. oligonodular), size of largest nodule (modelled as a continuous variable), presence of microscopic vascular invasion (MVI), and time horizon from surgery (5-year vs. 10-year). 330 patients were beyond the Milan criteria (32%) and 597 (58%) had MVI. The prevalence of MVI was 52% in patients within Milan criteria and 71% in those beyond (p<0.0001). In the 5-year transplant benefit analysis, nodule size and HCC number were positive predictors of transplant benefit, while MVI had a strong negative impact on NTT. Transplantation performed as an effective therapy (NTT <5) only in oligonodular HCC with largest diameter >3cm (beyond conventional LT criteria) when MVI was absent. The 10-year scenario increased drastically the transplant benefit in all subgroups of resectable patients, and LT became an effective therapy (NTT <5) for all patients without MVI whenever tumor extension and for oligonodular HCC with MVI within conventional LT criteria. Based on NTT analysis, the adopted time horizon (5-year vs. 10-year scenario) is the main factor influencing the benefit of LT in patients with resectable HCC and Child A cirrhosis.

Hepatopulmonary syndrome in children - is conventional liver transplantation always needed?

Hepatopulmonary syndrome (HPS) is the association of liver disease, hypoxemia, and intrapulmonary vascular dilatations. There are little data on the management of HPS in children other than conventional orthotopic liver transplantation (OLT). To describe the patient characteristics, mode of diagnosis, treatment, and outcomes of children with HPS at our center. Retrospective review of patients diagnosed with HPS between 1997 and 2007 after IRB approval. There were 10 patients, six females; median age at diagnosis of HPS was 12 yr. Six with cirrhosis underwent OLT and had subsequent resolution of HPS and are stable at last follow-up. Of the remaining four, two had cirrhosis. HPS resolved without conventional OLT in the following four patients: hepatitis C after antiviral treatment, biliary atresia with portal hypertension after transjugular intrahepatic portosystemic shunting, Abernethy syndrome after auxiliary partial OLT, and in a child with splenic vein thrombosis after splenectomy. Our series shows resolution of HPS in all patients and 100% survival after conventional OLT. Four children had resolution of HPS after surgical or medical treatments other than conventional OLT. Careful review of clinical status and underlying pathophysiology and anatomy at diagnosis of HPS should inform treatment decisions.

Living-related liver transplantation: implication for the anaesthetist

Living donor liver transplantation, originally introduced about a decade ago to overcome paediatric cadaveric organ shortage, has rapidly gained acceptance within the transplant community and is nowadays almost routinely applied to the growing number of adult and paediatric patients awaiting a live-saving liver transplantation. In fact its introduction has contributed to a continuing decrease of waiting list deaths. The risk of potential complications and even death for the donor increases with the extent of liver tissue resected. Better preoperative evaluation of suitability, refinement of surgical technique and smarter anaesthetic management, based on extended knowledge of underlying pathophysiology, have made the procedure safer for donors, with low morbidity and even lower mortality rates, tending towards zero in experienced centres. Despite these improvements, a certain risk is inherent. Yet from an ethical point of view it has to remain unacceptable especially because donors are otherwise healthy people and their only motives are altruistic. The procedure of living donor liver transplantation like conventional liver transplantation involves various disciplines, each of which contributes in a specific manner. There is a broad scope of issues that anaesthetists are responsible for and these largely depend on the department and hospital requirements. These issues may range from perioperative anaesthetic management and pain relief, to--and there are definite continental differences--the coordination of donor evaluation, intensive care management, postoperative complication management, as well as psychological support for donors, recipients and their relatives. In this paper we review and summarize the potential impact of findings and advances made in this particular field as described by the most important articles published during the past year.

Evaluation of 100 patients for living donor liver transplantation

The initial success of living donor liver transplantation (LDLT) in the United States has resulted in a growing interest in this procedure. The impact of LDLT on liver transplantation will depend in part on the proportion of patients considered medically suitable for LDLT and the identification of suitable donors. We report the outcome of our evaluation of the first 100 potential transplant recipients for LDLT at the University of Colorado Health Sciences Center (Denver, CO). All patients considered for LDLT had first been approved for conventional liver transplantation by the Liver Transplant Selection Committee and met the listing criteria of United Network for Organ Sharing status 1, 2A, or 2B. Once listed, those patients deemed suitable for LDLT were given the option to consider LDLT and approach potential donors. Donors were evaluated with a preliminary screening questionnaire, followed by formal evaluation. Of the 100 potential transplant recipients evaluated, 51 were initially rejected based on recipient characteristics that included imminent cadaveric transplantation (8 patients), refusal of evaluation (4 patients), lack of financial approval (6 patients), and medical, psychosocial, or surgical problems (33 patients). Of the remaining 49 patients, considered ideal candidates for LDLT, 24 patients were unable to identify a suitable donor for evaluation. Twenty-six donors were evaluated for the remaining 25 potential transplant recipients. Eleven donors were rejected: 9 donors for medical reasons and 2 donors who refused donation after being medically approved. The remaining 15 donor-recipient pairs underwent LDLT. Using our criteria for the selection of recipients and donors for LDLT gave the following results: (1) 51 of 100 potential transplant recipients (51%) were rejected for recipient issues, (2) only 15 of the remaining 49 potential transplant recipients (30%) were able to identify an acceptable donor, and (3) 15 of 100 potential living donor transplant recipients (15%) were able to identify a suitable donor and undergo LDLT. Recipient characteristics and donor availability may limit the widespread use of LDLT. However, careful application of LDLT to patients at greatest risk for dying on the waiting list may significantly reduce waiting list mortality.

Innovations in liver surgery through transplantation from living donors

ZusammenfassungDie Transplantation mit Lebendspende wurde in den 1990er Jahren in die klinische Routine übernommen. Nachdem zunächst die Resultate nicht zufrieden stellend waren, werden heute Ergebnisse erreicht, die denen der konventionellen Lebertransplantation gleich kommen. Durch eine wenig-invasive Diagnostik ist es derzeit bereits in einem Untersuchungsgang möglich die Qualität des potenziellen Spenderorgans zu beurteilen, fokale Läsionen auszuschließen und anatomische Varianten, die die Strategie der Entnahme beeinflussen, zu beschreiben. Die Spenderorperation erfolgt als Leberresektion ohne Hilusokklusion nach Feststellung anatomischer Gallengangsvarianten (insbesondere für die Spende des rechten Leberlappens) und der Lage der mittleren Lebervene. Für die Rekonstruktion von Gallengängen und Gefäßen werden mikrochirurgische Techniken genutzt. Mit der Lebendspende ist es möglich die komplexen Veränderungen nach einer Leberresektion im Menschen zu untersuchen. Diese chirurgisch-technischen Verfahren sowie die pathophysiologischen postoperativen Veränderungen können zwanglos auf komplexe onkologische Leberoperationen übertragen werden. Eine Therapieoptimierung und Risikosenkung werden möglich.

Evaluation of 100 patients for living donorliver transplantation

The initial success of living donor liver transplantation (LDLT) in the United States has resulted in a growing interest in this procedure. The impact of LDLT on liver transplantation will depend in part on the proportion of patients considered medically suitable for LDLT and the identification of suitable donors. We report the outcome of our evaluation of the first 100 potential transplant recipients for LDLT at the University of Colorado Health Sciences Center (Denver, CO). All patients considered for LDLT had first been approved for conventional liver transplantation by the Liver Transplant Selection Committee and met the listing criteria of United Network for Organ Sharing status 1, 2A, or 2B. Once listed, those patients deemed suitable for LDLT were given the option to consider LDLT and approach potential donors. Donors were evaluated with a preliminary screening questionnaire, followed by formal evaluation. Of the 100 potential transplant recipients evaluated, 51 were initially rejected based on recipient characteristics that included imminent cadaveric transplantation (8 patients), refusal of evaluation (4 patients), lack of financial approval (6 patients), and medical, psychosocial, or surgical problems (33 patients). Of the remaining 49 patients, considered ideal candidates for LDLT, 24 patients were unable to identify a suitable donor for evaluation. Twenty-six donors were evaluated for the remaining 25 potential transplant recipients. Eleven donors were rejected: 9 donors for medical reasons and 2 donors who refused donation after being medically approved. The remaining 15 donor-recipient pairs underwent LDLT Using our criteria for the selection of recipients and donors for LDLT gave the following results: (1) 51 of 100 potential transplant recipients (51%) were rejected for recipient issues, (2) only 15 of the remaining 49 potential transplant recipients (30%) were able to identify an acceptable donor, and (3) 15 of 100 potential living donor transplant recipients (15%) were able to identify a suitable donor and undergo LDLT Recipient characteristics and donor availability may limit the widespread use of LDLT However, careful application of LDLT to patients at greatest risk for dying on the waiting list may significantly reduce waiting list mortality.

Liver Bridging Techniques in the Treatment of Acute Liver Failure

The introduction of orthotopic liver transplantation in the management of acute liver failure has dramatically increased the survival rates of patients at the cost of removing the patient's native liver and life-long dependence on immunosuppression. However, it is well known that in many patients with acute liver failure the diseased liver has the potential to recover. Death in these patients is often due to increased intra-cranial pressure or infection. Liver bridging techniques are assigned to temporarily provide liver function and enable the native liver to recover in patients with acute liver failure. They represent an attractive alternative to conventional liver transplantation in the management of acute liver failure, since after recovery of the native liver the patient is freed from immuno-suppression with all associated side-effects and risks. Auxiliary liver transplantation, artificial liver support devices and hepatocyte transplantation represent different ways of bridging liver function in acute liver failure. The aim of this review is to present the ideas and principles of these three different liver bridging techniques. We will discuss the relative importance and the future potential of theses bridging techniques in the treatment of acute liver failure by comparing the experimental and clinical results.

Pulmonary evolution in conventional liver transplantation with venovenous bypass and the piggyback method

Pulmonary evolution in conventional liver transplantation with venovenous bypass and the piggyback method

Liver transplantation with cavoportal hemitransposition in the presence of diffuse portal vein thrombosis.

Orthotopic liver transplantation is possible even in the presence of recipient portal vein thrombosis, provided that hepatopetal portal flow to the graft can be restored. On rare occasions this is not possible due to diffuse thrombosis of the portal venous system. In these cases, successful liver transplantation has been considered impossible. Portocaval transposition was introduced in the pretransplantation era to study the effect of systemic venous flow on the liver and has been used in three patients for the treatment of glycogen storage disease. We used portocaval hemitransposition (portal perfusion with inflow from the inferior vena cava) in liver transplantation when portal inflow to the graft was not feasible. We are reporting the collective experience of nine patients from four liver transplant centers. Cavoportal hemitransposition was used in nine patients. In seven of these cases, the technique was used during the original transplant (primary group). In two cases, it was used after the portal inflow to the first transplant had clotted (secondary group). Five of seven patients in the primary group are alive after intervals of 6-11 months. The two patients in the rescue group died. In the successful cases, liver function and histology were indistinguishable from those of conventional liver transplantation. Ascites disappeared within 3-4 months and the patients were able to return to their normal activities. Postoperative variceal bleeding necessitated splenectomy and gastric devascularization in one case and splenic artery embolization in another case. Bleeding was controlled in both these cases. Splenectomy and gastric devascularization were performed prophylactically in one patient with a history of variceal bleeding in order to prevent this complication after transplantation. Portocaval hemitransposition maybe useful in liver transplantation when hepatopetal flow to the liver graft cannot be established by other techniques. Rescue after failure of conventional technique was not possible in two patients.