Challenge In Liver Transplantation Research Articles

Fifty years of Australian gastroenterology and hepatology: A golden era of contributions to the region

Fifty years of Australian gastroenterology and hepatology: A golden era of contributions to the region

Liver Transplantation in the Ethnic Minority Population: Challenges and Prospects

In the USA, end-stage liver disease (ESLD) is a major cause of morbidity and mortality among ethnic minorities. Ethnic populations vary with respect to chronic liver disease prevalence, access to transplantation, and therapeutic outcomes post liver transplantation. These ethnic differences present unique challenges to healthcare professionals involved in the care of patients with chronic liver disease prior and post transplantation. This review will discuss the variations and challenges of liver transplantation in the ethnic minority population.

Twenty years' follow-up of portal vein conduits in liver transplantation

Portal vein problems remain a formidable challenge in liver transplantation. In select situations, a portal vein conduit can provide a solution. No long-term results have been reported. This study was designed to assess the impact of portal vein conduits on graft survival after liver transplantation and the safety of portal vein conduits and to establish the long-term results (up to 20 years) of portal vein conduits. Data from 2370 adult liver transplants were prospectively collected into a computerized research database and analyzed. All portal vein conduits were constructed from the donor iliac vein obtained at the liver retrieval. Portal vein conduits were required in 35 (1.5%) first transplants. The long-term (up to 20 years of follow-up) graft survival after liver transplantation using portal vein conduits was excellent and comparable to that of the control group. The graft survival was 65% with the conduit versus 66% without the conduit at 5 years of follow-up, 58% versus 51% at 10 years, and 48% versus 35% at 15 years. There was a higher rate (8.6% versus 1.4%) of portal vein thrombosis after the portal vein conduit, and the majority occurred in the first 3 months after transplantation. For the same time period, there was no statistically significant difference in graft survival or patient survival for the retransplants with and without portal vein conduits. There was no statistically significant difference in graft survival or patient survival for the transplants with portal vein conduits and with portal vein thrombendvenectomy. In conclusion, portal vein conduits can be used safely for liver transplantation with no negative impact on long-term graft survival or patient survival. Despite the higher rate of portal vein thrombosis in the immediate postoperative period, excellent long-term results can be obtained.

Twenty years of follow-up of aortohepatic conduits in liver transplantation

Arterial problems remain a formidable challenge in liver transplantation. In many situations, an aortohepatic conduit can provide a solution. No long-term results (over 5 years) have been reported. This study was designed to assess the impact of aortohepatic conduits on graft survival after liver transplantation and the safety of aortohepatic conduits and to establish the long-term results (up to 20 years) of aortohepatic conduits. Data from 2346 adult liver transplants were prospectively collected into the computerized database and analyzed. In the majority of cases, arterial conduits were constructed from the donor iliac artery obtained at the liver retrieval. Aortohepatic conduits were required in 149 (6.4%) first transplants. The long-term graft survival after liver transplantation using aortohepatic conduits was excellent and comparable to that of the control group. The graft survival was 59% with the conduit versus 67% without the conduit at 5 years of follow-up, 50% versus 52% at 10 years, and 33% versus 35% at 15 years. With up to 20 years of follow-up, there was no statistically significant difference in graft survival, patient survival, hepatic artery complications, or biliary complications. For the same time period, there was no statistically significant difference in graft survival or patient survival for the retransplants with and without aortohepatic conduits. In conclusion, in experienced hands, aortohepatic conduits can be used safely for liver transplantation with no negative impact on long-term graft survival, patient survival, hepatic artery complications, or biliary complications. Excellent long-term results can be obtained.

Preemptive treatment of fungal infection: has its time arrived in liver transplantation?

Background Invasive fungal infection remains a major challenge in liver transplantation and the mortality rate is high. Early diagnosis and treatment are required for better results. Patients We prospectively measured plasma (1 → 3)β-d glucan (BDG) levels in 180 living donor liver transplant recipients for 1 year after surgery. Fungal infection was defined as proposed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group. Preemptive treatment (intravenous fluconazole and trimethoprim-sulfamethoxazole) was started when the BDG level was greater than 40 pg/ml. Results Twenty-four patients (13%) were diagnosed with invasive fungal infection. The responsible pathogens included Candida spp. in 14 cases, Aspergillus fumigatus in 5, Cryptococcus neoformans in 3, and Pneumocystis jiroveci in 2. Preemptive treatment was performed in 22% of patients (n = 40). Renal impairment and mild gastrointestinal intolerance due to the drugs were observed in 28% (11/40) of patients during treatment. Among them 14 patients were diagnosed with fungal infection including seven candidiasis, five aspergillosis, and two Pneumocystis jiroveci pneumonia. The sensitivity and specificity of BDG for overall fungal infection was 58% and 83%, respectively, with a positive predictive value of 35% and a negative predictive value of 93%, and a positive likelihood ratio of 3.41 and a negative likelihood ratio of 1.98. The overall mortality for fungal infection in our series was 0.6%. Conclusion Although the sensitivity and positive predictive value were low, the low mortality rate after fungal infection and the mild side effects of the preemptive treatment might justify our therapeutic strategy. Based on the effectiveness, this strategy warrants further investigation.

Preemptive Treatment of Fungal Infection Based on Plasma (1 → 3)β-D-Glucan Levels after Liver Transplantation

Invasive fungal infection remains a major challenge in liver transplantation and the mortality rate is high. Early diagnosis and treatment are required for better results. We prospectively measured plasma (1 --> 3)beta-D-glucan (BDG) levels in 180 living donor liver transplant recipients for 1 year after surgery. Fungal infection was defined as proposed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group. Preemptive treatment (intravenous fluconazole and trimethoprim-sulfamethoxazole) was started when the BDG level was greater than 40 pg/ml. Twenty-four patients (13%) were diagnosed with invasive fungal infection. The responsible pathogens included Candida spp. in 14 cases, Aspergillus fumigatus in 5, Cryptococcus neoformans in 3, and Pneumocystis jiroveci in 2. Preemptive treatment was performed in 22% of patients (n = 40). Renal impairment and mild gastrointestinal intolerance due to the drugs were observed in 28% (11/40) of patients during treatment. Among them 14 patients were diagnosed with fungal infection including seven candidiasis, five aspergillosis, and two Pneumocystis jiroveci pneumonia. The sensitivity and specificity of BDG for overall fungal infection was 58% and 83%, respectively, with a positive predictive value of 35% and a negative predictive value of 93%, and a positive likelihood ratio of 3.41 and a negative likelihood ratio of 1.98. The overall mortality for fungal infection in our series was 0.6%. Although the sensitivity and positive predictive value were low, the low mortality rate after fungal infection and the mild side effects of the preemptive treatment might justify our therapeutic strategy. Based on the effectiveness, this strategy warrants further investigation.

Management of portal vein thrombosis in liver transplantation: influence on morbidity and mortality

Splanchnic thrombosis is a surgical challenge in liver transplantation (LT). The aim of this study was to analyze our experience in the management of portal vein thrombosis, and its influence on evolution. The aim of this study was to analyze our experience in the management of portal vein thrombosis, and its influence on evolution. Between 1999 and 2004, 366 liver transplants were performed in 335 patients. Forty-two patients [12.5%: portal vein thrombosis (PVT) group] had portal thrombosis at the time of LT. We analyzed the technical aspects and compared their evolution with a group of patients without portal thrombosis (n = 293; no-PVT group). Retransplantations were excluded. Of the 42 patients with thrombosis, 18 had partial thrombosis and 16 complete thrombosis [six included the proximal superior mesenteric vein (SMV) and in two the whole splanchnic system]. In 12 cases, usual T-T anastomosis was performed and in 16 cases a thrombectomy was carried out; there were five cases of anastomosis at confluence of the SMV, five cases of anastomosis to a collateral vein, three cases of venous graft, and one case of cavoportal hemitransposition. The operative time was higher in PVT group (417 +/- 103 min vs. 363 +/- 83; p = 0.0005), as RBC transfusion (2.4 +/- 3.1 vs. 1.9 +/- 2.3; p = 0.04), and hospital stay (20.9 +/- 14.9 d vs. 15.1 +/- 10.6; p = 0.002). However, there were no differences in hospital mortality (4% vs. 7.8%; p = 0.98), primary dysfunction (4.8% vs. 7.8%; p = 0.44), or three-yr-actuarial survival (75% vs. 77%; p = 0.95). The incidence of post-transplant thrombosis was higher in the PVT group (15% vs. 2.4%; p = 0.0005). Portal thrombosis is associated with greater operative complexity and rethrombosis, but has no influence on overall morbidity and mortality.

The Liver: A Special Case in Transplantation Tolerance

Liver transplants are not often rejected in patients weaned from immunosuppression and are spontaneously accepted in some animal models. We review past and recent findings of liver transplantation and propose a unified model in which several mechanisms act in concert to induce and maintain tolerance in both naïve and effector T cell compartments. First, passenger leukocytes migrate to lymphoid tissues and induce apoptosis of alloreactive naïve T cells. Second, antigen-specific activation and subsequent deletion of naïve and effector cells within the liver itself purge the repertoire of alloreactive T cells. Other mechanisms such as microchimerism and migration of donor dendritic cells to the thymus may play a predominant role in maintaining tolerance, and soluble major histocompatibility complex molecules, donor peptides, and regulatory T cells may participate in the induction and maintenance phases. Thus, the major challenge in liver transplantation will be to favor these tolerogenic processes while developing strategies that specifically inhibit alloreactive memory T cells.

Challenges in liver transplantation: from organ donation to long−term monitoring

Liver transplantation has evolved from an experimental procedure to being accepted as a successful therapy for both acute liver failure and chronic liver diseases. Shortage of donor organs has become a real issue leading to some patients dying on the transplant waiting list. Having received a liver transplant, patients have good survival outcomes and can lead relatively normal lives with some considerations for effects of immunosuppressive therapy. This article considers the expansion of the organ donor pool by utilizing nonheart-beating organ donation, reviews health-related quality-of-life post-liver transplantation and examines some aspects of medication and long-term surveillance of these patients.

Improvement of rat liver graft quality by pifithrin-alpha-mediated inhibition of hepatocyte necrapoptosis.

Early graft dysfunction due to ischemia reperfusion injury remains a major clinical challenge in liver transplantation. Because apoptosis may contribute to graft dysfunction, we studied whether transient inhibition of p53 is capable of improving graft quality by reducing apoptotic cell death. Rat livers were harvested and stored for 24 hours or 48 hours in a 4 degrees C solution containing either pifithrin-alpha (PFT-alpha), a specific p53-inhibitor, or the vehicle dimethyl-sulfoxide. Storage was followed by 2-hour reperfusion with 37 degrees C Krebs-Henseleit buffer in an isolated liver perfusion system. Besides caspase-3 activation, apoptosis was quantified using fluorescence microscopy and hematoxylin-eosin histology. Trypan blue allowed for assessment of cell membrane damage, indicating both secondary apoptosis and primary necrosis. Bile flow, oxygen consumption, K(+)-excretion and enzyme release served as indicators of overall graft quality. Upon 2-hour reperfusion, livers developed procaspase activation as well as a mixture of apoptotic and necrotic cell death, representing necrapoptosis. In livers that had been stored for 48 hours, necrapoptotic injury was more pronounced compared with that after 24-hour storage. PFT-alpha effectively attenuated caspase activation as well as hepatocellular apoptosis and necrosis. Attenuation of both modes of cell death by PFT-alpha was associated with improved liver function, metabolism, and integrity. Experiments with the caspase inhibitor z-VAD-fmk confirmed that apoptosis is one mode of cell death in cold ischemia reperfusion. In conclusion, inhibition of p53-dependent apoptosis by PFT-alpha reduces hepatic preservation-reperfusion injury and improves primary organ function and metabolism. Fortification of the preservation solution with PFT-alpha may represent a promising and easily applicable approach to mitigate reperfusion injury in liver transplants.

Ethical and psychosocial challenges in liver transplantation

Ethical and psychosocial challenges in liver transplantation

LIVER TRANSPLANTATION AT THE MILLENNIUM: Past, Present, and Future

During the past 3 decades, liver transplantation has achieved such acceptance that more than 12,000 qualified recipients are listed for liver transplantation in the United States, but unfortunately just over 4000 cadaver donor organs are available each year. Thus, given the increasing disparity between the number of potential recipients and available cadaver organs, the current challenge in liver transplantation is to optimize the outcome of liver transplantation from this limited resource. Currently under way is re-evaluation of selection criteria to use these 4000 cadaver liver grafts most effectively by striking the proper balance between medical urgency and utility. In parallel with this re-evaluation, there is ongoing expansion of cadaver split-liver transplantation and adult living related and unrelated liver transplantation. Hoped-for but as yet unachieved developments in liver transplantation are xenotransplantation, hepatocyte transplantation, and liver-directed gene therapy. Liver transplantation has come a long way from the initial, unsuccessful human transplantations in 1963, but many challenges remain.

Tomorrow’s challenge in liver transplantation: diminishing the imbalance between donor organ availability and need

Tomorrow’s challenge in liver transplantation: diminishing the imbalance between donor organ availability and need