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Einstein (Sao Paulo, Brazil) 2015In 1958 Francis Moore described the orthotopic liver transplantation technique in dogs. In 1963, Starzl et al. performed the first liver transplantation. In the first... (Review)
Review
In 1958 Francis Moore described the orthotopic liver transplantation technique in dogs. In 1963, Starzl et al. performed the first liver transplantation. In the first five liver transplantations no patient survived more than 23 days. In 1967, stimulated by Calne who used antilymphocytic serum, Starzl began a successful series of liver transplantation. Until 1977, 200 liver transplantations were performed in the world. In that period, technical problems were overcome. Roy Calne, in 1979, used the first time cyclosporine in two patients who had undergone liver transplantation. In 1989, Starzl et al. reported a series of 1,179 consecutives patients who underwent liver transplantation and reported a survival rate between one and five years of 73% and 64%, respectively. Finally, in 1990, Starzl et al. reported successful use of tacrolimus in patents undergoing liver transplantation and who had rejection despite receiving conventional immunosuppressive treatment. Liver Transplantation Program was initiated at Hospital Israelita Albert Einstein in 1990 and so far over 1,400 transplants have been done. In 2013, 102 deceased donors liver transplantations were performed. The main indications for transplantation were hepatocellular carcinoma (38%), hepatitis C virus (33.3%) and alcohol liver cirrhosis (19.6%). Of these, 36% of patients who underwent transplantation showed biological MELD score > 30. Patient and graft survival in the first year was, 82.4% and 74.8%, respectively. A major challenge in liver transplantation field is the insufficient number of donors compared with the growing demand of transplant candidates. Thus, we emphasize that appropriated donor/receptor selection, allocation and organ preservation topics should contribute to improve the number and outcomes in liver transplantation.
Topics: Animals; Brazil; Dogs; Graft Rejection; Graft Survival; History, 20th Century; History, 21st Century; Humans; Kaplan-Meier Estimate; Liver Transplantation; Treatment Outcome
PubMed: 25993082
DOI: 10.1590/S1679-45082015RW3164 -
International Journal of Molecular... Nov 2020The liver is a unique organ with an abundant regenerative capacity. Therefore, partial hepatectomy (PHx) or partial liver transplantation (PLTx) can be safely performed.... (Review)
Review
The liver is a unique organ with an abundant regenerative capacity. Therefore, partial hepatectomy (PHx) or partial liver transplantation (PLTx) can be safely performed. Liver regeneration involves a complex network of numerous hepatotropic factors, cytokines, pathways, and transcriptional factors. Compared with liver regeneration after a viral- or drug-induced liver injury, that of post-PHx or -PLTx has several distinct features, such as hemodynamic changes in portal venous flow or pressure, tissue ischemia/hypoxia, and hemostasis/platelet activation. Although some of these changes also occur during liver regeneration after a viral- or drug-induced liver injury, they are more abrupt and drastic following PHx or PLTx, and can thus be the main trigger and driving force of liver regeneration. In this review, we first provide an overview of the molecular biology of liver regeneration post-PHx and -PLTx. Subsequently, we summarize some clinical conditions that negatively, or sometimes positively, interfere with liver regeneration after PHx or PLTx, such as marginal livers including aged or fatty liver and the influence of immunosuppression.
Topics: Animals; Fatty Liver; Hepatectomy; Humans; Liver; Liver Regeneration; Liver Transplantation
PubMed: 33182515
DOI: 10.3390/ijms21218414 -
World Journal of Gastroenterology May 2016Great progress has been made in the field of liver transplantation over the past two decades. This progress, however, also brings up the next set of challenges: First,... (Review)
Review
Great progress has been made in the field of liver transplantation over the past two decades. This progress, however, also brings up the next set of challenges: First, organ shortage remains a major limitation, and accounts for a large proportion of wait list mortality. While living donation has successfully increased the total number of liver transplants done in Asian countries, the total number of such transplants has been stagnant in the western hemisphere. As such, there has been a significant effort over the past decade to increase the existing deceased donor pool. This effort has resulted in a greater use of liver allografts following donation after cardiac death (DCD) along with marginal and extended criteria donors. Improved understanding of the pathophysiology of liver allografts procured after circulatory arrest has not only resulted in better selection and management of DCD donors, but has also helped in the development of mechanical perfusion strategies. Early outcomes demonstrating the clinical applicability of both hypothermic and normothermic perfusion and its potential to impact patient survival and allograft function have generated much interest. Second, long-term outcomes of liver transplant recipients have not improved significantly, as recipients continue to succumb to complications of long-term immunosuppression, such as infection, malignancy and renal failure. Furthermore, recent evidence suggests that chronic immune-mediated injury to the liver may also impact graft function.
Topics: Allografts; Animals; Donor Selection; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Liver Transplantation; Perfusion; Risk Factors; Time Factors; Tissue Donors; Treatment Outcome
PubMed: 27182155
DOI: 10.3748/wjg.v22.i18.4438 -
Journal of Hepatology Jun 2023With the increasing number of accepted candidates on waiting lists worldwide, there is an urgent need to expand the number and the quality of donor livers. Dynamic... (Review)
Review
With the increasing number of accepted candidates on waiting lists worldwide, there is an urgent need to expand the number and the quality of donor livers. Dynamic preservation approaches have demonstrated various benefits, including improving liver function and graft survival, and reducing liver injury and post-transplant complications. Consequently, organ perfusion techniques are being used in clinical practice in many countries. Despite this success, a proportion of livers do not meet current viability tests required for transplantation, even with the use of modern perfusion techniques. Therefore, devices are needed to further optimise machine liver perfusion - one promising option is to prolong machine liver perfusion for several days, with ex situ treatment of perfused livers. For example, stem cells, senolytics, or molecules targeting mitochondria or downstream signalling can be administered during long-term liver perfusion to modulate repair mechanisms and regeneration. Besides, today's perfusion equipment is also designed to enable the use of various liver bioengineering techniques, to develop scaffolds or for their re-cellularisation. Cells or entire livers can also undergo gene modulation to modify animal livers for xenotransplantation, to directly treat injured organs or to repopulate such scaffolds with "repaired" autologous cells. This review first discusses current strategies to improve the quality of donor livers, and secondly reports on bioengineering techniques to design optimised organs during machine perfusion. Current practice, as well as the benefits and challenges associated with these different perfusion strategies are discussed.
Topics: Animals; Liver Transplantation; Organ Preservation; Liver; Perfusion; Bioengineering
PubMed: 37208105
DOI: 10.1016/j.jhep.2023.02.009 -
Journal of Hepatology Aug 2023Ischemia-reperfusion injury (IRI) has thus far been considered as an inevitable component of organ transplantation, compromising outcomes, and limiting organ... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIMS
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.
METHODS
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. The primary endpoint was the incidence of early allograft dysfunction. Secondary endpoints included complications related to graft IRI.
RESULTS
Out of 68 randomized patients, 65 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 two recipients (6%) randomized to IFLT and in eight (24%) randomized to CLT (difference -18%; 95% CI -35% to -1%; p = 0.044). Post-reperfusion syndrome occurred in three recipients (9%) randomized to IFLT and in 21 (64%) randomized to CLT (difference -54%; 95% CI -74% to -35%; p <0.001). Non-anastomotic biliary strictures diagnosed with protocol magnetic resonance cholangiopancreatography at 12 months were observed in two recipients (8%) randomized to IFLT and in nine (36%) randomized to CLT (difference, -28%; 95% CI -50% to -7%; p = 0.014). The comprehensive complication index at 1 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 = 0.025).
CONCLUSIONS
Among patients with end-stage liver disease, IFLT significantly reduced complications related to IRI compared to a conventional approach.
CLINICAL TRIAL REGISTRATION
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 a 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.
Topics: Humans; Liver Transplantation; End Stage Liver Disease; Ischemia; Liver; Reperfusion Injury; Perfusion; Organ Preservation
PubMed: 37086919
DOI: 10.1016/j.jhep.2023.04.010 -
Journal of Hepatology Jun 2023Liver transplantation (LT) is a life-saving treatment for individuals with end-stage liver disease. The management of LT recipients is complex, predominantly because of... (Review)
Review
Liver transplantation (LT) is a life-saving treatment for individuals with end-stage liver disease. The management of LT recipients is complex, predominantly because of the need to consider demographic, clinical, laboratory, pathology, imaging, and omics data in the development of an appropriate treatment plan. Current methods to collate clinical information are susceptible to some degree of subjectivity; thus, clinical decision-making in LT could benefit from the data-driven approach offered by artificial intelligence (AI). Machine learning and deep learning could be applied in both the pre- and post-LT settings. Some examples of AI applications pre-transplant include optimising transplant candidacy decision-making and donor-recipient matching to reduce waitlist mortality and improve post-transplant outcomes. In the post-LT setting, AI could help guide the management of LT recipients, particularly by predicting patient and graft survival, along with identifying risk factors for disease recurrence and other associated complications. Although AI shows promise in medicine, there are limitations to its clinical deployment which include dataset imbalances for model training, data privacy issues, and a lack of available research practices to benchmark model performance in the real world. Overall, AI tools have the potential to enhance personalised clinical decision-making, especially in the context of liver transplant medicine.
Topics: Humans; Liver Transplantation; Artificial Intelligence; Deep Learning; End Stage Liver Disease; Machine Learning
PubMed: 37208107
DOI: 10.1016/j.jhep.2023.01.006 -
American Journal of Transplantation :... Jan 2016Intestine and intestine-liver transplant plays an important role in the treatment of intestinal failure, despite decreased morbidity associated with parenteral...
Intestine and intestine-liver transplant plays an important role in the treatment of intestinal failure, despite decreased morbidity associated with parenteral nutrition. In 2014, 210 new patients were added to the intestine transplant waiting list. Among prevalent patients on the list at the end of 2014, 65% were waiting for an intestine transplant and 35% were waiting for an intestine-liver transplant. The pretransplant mortality rate decreased dramatically over time for all age groups. Pretransplant mortality was highest for adult candidates, at 22.1 per 100 waitlist years compared with less than 3 per 100 waitlist years for pediatric candidates, and notably higher for candidates for intestine-liver transplant than for candidates for intestine transplant without a liver. Numbers of intestine transplants without a liver increased from a low of 51 in 2013 to 67 in 2014. Intestine-liver transplants increased from a low of 44 in 2012 to 72 in 2014. Short-gut syndrome (congenital and other) was the main cause of disease leading to both intestine and intestine-liver transplant. Graft survival improved over the past decade. Patient survival was lowest for adult intestine-liver recipients and highest for pediatric intestine recipients.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Graft Survival; Humans; Immunosuppressive Agents; Intestinal Diseases; Intestines; Liver Transplantation; Male; Middle Aged; Prevalence; Tissue Donors; Treatment Outcome; United States; Waiting Lists; Young Adult
PubMed: 26755265
DOI: 10.1111/ajt.13669 -
Transplant International : Official... Apr 2019Kidney injury is frequently seen in patients with end-stage liver disease from cirrhosis and liver failure. Among selected patients, simultaneous liver kidney (SLK)... (Review)
Review
Kidney injury is frequently seen in patients with end-stage liver disease from cirrhosis and liver failure. Among selected patients, simultaneous liver kidney (SLK) transplantation provides improved post-transplant graft and patient outcomes compared to liver transplantation (LT) alone. We conducted the review of the existing literature on SLK transplant criteria and outcomes. Since the introduction of the model for end-stage disease (MELD) score in 2002, there has been an increased use of SLK transplantation. The criteria for SLK allocation are relatively homogeneous among patients with end-stage renal disease with cirrhosis and among patients with cirrhosis and chronic kidney disease. However, these are quite heterogeneous among patients with cirrhosis and acute kidney injury (AKI), mainly because of inability to accurately differentiate cause of AKI, especially hepatorenal syndrome versus intrarenal aetiology. Clearly, there is an unmet need of urine biomarkers of tubular injury and/or clinical models to accurately stratify AKI aetiology and to predict renal recovery after LT as basis to best utilize the scarce donor kidney pool. In this regard, it remains to be seen whether recently implemented policies by the organ procurement transplant network can fulfil the goal of saving donor kidneys and optimal allocation of SLK.
Topics: Acute Kidney Injury; Biomarkers; Glomerular Filtration Rate; Humans; Kidney Transplantation; Liver Cirrhosis; Liver Transplantation; Tissue and Organ Procurement
PubMed: 30548094
DOI: 10.1111/tri.13388 -
Chirurgia (Bucharest, Romania : 1990) 2017In 50 years after the first liver transplantation, the medical world has witnessed the liver transplantation to become one of the widely recognized and leading branches... (Review)
Review
In 50 years after the first liver transplantation, the medical world has witnessed the liver transplantation to become one of the widely recognized and leading branches of surgery. In this period, liver transplantation combined with surgical technique, patient selection, advancements in anesthesia and postoperative care and increased experience has become the most effective treatment option in treatment of several acute and chronic liver diseases. Yet, the worldwide organ restriction and associated high mortality rates in organ transplantation waiting list has compelled referring to living donors in order to expand the donor pool. This paper explains liver transplantation indications from living donors, the surgical technique involved, the complications of the procedure and the medical treatments used.
Topics: Adult; Elective Surgical Procedures; Humans; Liver Diseases; Liver Transplantation; Living Donors; Patient Selection; Treatment Outcome
PubMed: 28675358
DOI: 10.21614/chirurgia.112.3.217 -
International Journal of Radiation... Mar 2019Orthotopic liver transplantation (OLT) has been effective in managing end-stage liver disease since the advent of cyclosporine immunosuppression therapy in 1980. The... (Review)
Review
Orthotopic liver transplantation (OLT) has been effective in managing end-stage liver disease since the advent of cyclosporine immunosuppression therapy in 1980. The major limitations of OLT are organ supply, monetary cost, and the burden of lifelong immunosuppression. Hepatocyte transplantation, as a substitute for OLT, has been an exciting topic of investigation for several decades. HT is potentially minimally invasive and can serve as a vehicle for delivery of personalized medicine through autologous cell transplant after modification ex vivo. However, 3 major hurdles have prevented large-scale clinical application: (1) availability of transplantable cells; (2) safe and efficient ex vivo gene therapy methods; and (3) engraftment and repopulation efficiency. This review will discuss new sources for transplantable liver cells obtained by lineage reprogramming, clinically acceptable methods of genetic manipulation, and the development of hepatic irradiation-based preparative regimens for enhancing engraftment and repopulation of transplanted hepatocytes. We will also review the results of the first 3 patients with genetic liver disorders who underwent preparative hepatic irradiation before hepatocyte transplantation.
Topics: Animals; Cell Proliferation; Genetic Therapy; Hepatocytes; Humans; Liver Transplantation; Safety
PubMed: 30503786
DOI: 10.1016/j.ijrobp.2018.11.016