Liver Transplantation: Current Challenges and New Perspectives

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Gastroenterology & Hepatopancreatobiliary Medicine".

Deadline for manuscript submissions: closed (25 January 2024) | Viewed by 8796

Special Issue Editor

Transplantation and HPB Surgery, Royal Prince Alfred Hospital, Sydney, Australia
Interests: ex vivo perfusion; organ preservation; transplant oncology; split liver; living donor; liver transplant outcome; tolerance; donor after cardiac death

Special Issue Information

Dear Colleagues,

Liver transplantation is an effective therapy for several patients with acute and chronic liver diseases, and selected patients with liver cancer.

In the last decade, refinements in perioperative management and surgical techniques have resulted in improved grafts and patient survival. However, several changing trends in liver transplantation have presented challenges. There is an increasing need for liver transplantation, primarily as a result of increased incidence of nonalcoholic steatohepatitis and cancer indications. Marginal grafts and donor after circulatory death donation have been more frequently used in order to expand the donor pool.

New technology for graft assessment and preservation have been introduced with promising results. Refinements in surgical procedures, including split liver and live donor liver transplantations, have expanded the organ pool. Indications for transplantation have been constantly broadened, including selected patients with cholangiocarcinoma and metastatic colorectal cancer.

Dr. Carlo Pulitano
Guest Editor

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Keywords

  • Ex vivo perfusion
  • organ preservation
  • transplant oncology
  • split liver
  • living donor
  • liver transplant outcome
  • tolerance
  • donor after cardiac death

Published Papers (5 papers)

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Research

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13 pages, 1585 KiB  
Article
Two Decades of Liver Transplants for Primary Biliary Cholangitis: A Comparative Study of Living Donors vs. Deceased Donor Liver Transplantations
by Esli Medina-Morales, Mohamed Ismail, Romelia Barba Bernal, Yazan Abboud, Leandro Sierra, Ana Marenco-Flores, Daniela Goyes, Behnam Saberi, Vilas Patwardhan and Alan Bonder
J. Clin. Med. 2023, 12(20), 6536; https://doi.org/10.3390/jcm12206536 - 15 Oct 2023
Cited by 1 | Viewed by 1033
Abstract
Primary biliary cholangitis (PBC) prompts liver transplantation (LT) due to cholestasis, cirrhosis, and liver failure. Despite lower MELD scores, recent studies highlight higher PBC waitlist mortality, intensifying the need for alternative transplantation strategies. Living donor liver transplant (LDLT) has emerged as a solution [...] Read more.
Primary biliary cholangitis (PBC) prompts liver transplantation (LT) due to cholestasis, cirrhosis, and liver failure. Despite lower MELD scores, recent studies highlight higher PBC waitlist mortality, intensifying the need for alternative transplantation strategies. Living donor liver transplant (LDLT) has emerged as a solution to the organ shortage. This study compares LDLT and deceased donor liver transplant (DDLT) outcomes in PBC patients via retrospective analysis of the UNOS database (2002–2021). Patient survival, graft failure, and predictors were evaluated through Kaplan–Meier and Cox-proportional analyses. Among 3482 DDLTs and 468 LDLTs, LDLT showed superior patient survival (92.3%, 89.1%, 87.6%, 85.0%, 77.2% vs. 91.5%, 88.3%, 86.3%, 82.2%, 71.0%; respectively; p = 0.02) with no significant graft survival difference at 1-, 2-, 3-, 5-, and 10-years post-LT (91.0%, 88.0%, 85.7%, 83.0%, 75.4% vs. 90.5%, 87.4%, 85.3%, 81.3%, 70.0%; respectively; p = 0.06). Compared to DCD, LDLT showed superior patient and graft survival (p < 0.05). Younger male PBC recipients with a high BMI, diabetes, and dialysis history were associated with mortality and graft failure (p < 0.05). Our study showed that LDLT had superior patient survival to DDLT. Predictors of poor post-LT outcomes require further validation studies. Full article
(This article belongs to the Special Issue Liver Transplantation: Current Challenges and New Perspectives)
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11 pages, 1643 KiB  
Article
A Multi-Centre Non-Interventional Study to Assess the Tolerability and Effectiveness of Extended-Release Tacrolimus (LCPT) in De Novo Liver Transplant Patients
by Thomas Soliman, Georg Gyoeri, Andreas Salat, Vladimír Mejzlík and Gabriela Berlakovich
J. Clin. Med. 2023, 12(7), 2537; https://doi.org/10.3390/jcm12072537 - 28 Mar 2023
Cited by 1 | Viewed by 1092
Abstract
Background: Available tacrolimus formulations exhibit substantial inter- and intra-individual variability in absorption and metabolism. The present non-interventional cohort study aimed to assess the tolerability and effectiveness of the once-daily tacrolimus formulation, LCPT, in hepatic allograft recipients in real life. Materials and methods: This [...] Read more.
Background: Available tacrolimus formulations exhibit substantial inter- and intra-individual variability in absorption and metabolism. The present non-interventional cohort study aimed to assess the tolerability and effectiveness of the once-daily tacrolimus formulation, LCPT, in hepatic allograft recipients in real life. Materials and methods: This study was conducted in Austria and the Czech Republic between July 2016 and August 2019. Patients aged ≥ 18 years old received LCPT per the approved label and local clinical routine. All the participants provided informed consent. Patients newly treated with tacrolimus (de novo) directly after transplantation were observed for six months. The relevant clinical variables were tacrolimus trough level (TL), total daily dose (TDD), number of dose adjustments, kidney and liver function, and tolerability. Results: Of the 70 analyzed patients, 72.9% were male and 85.7% were aged < 65 years old. The mean (SD) time to achieve tacrolimus target TL was 6.4 (4.6) days after 4.4 (4.0) dose adjustments; thereafter, TL remained stable throughout observation at approximately 8 ng/mL. The LCPT TDD at initiation was 8 mg and decreased by a median of 41.4% to 5 mg at 6 months. Liver function continuously improved, and kidney function remained stable. LCPT was well tolerated with 24 adverse events in eight patients (17 related to immunosuppression, mostly mild renal insufficiency, and hematological adverse events); two serious unrelated adverse events were reported (atrial flutter and liver dysfunction). Conclusions: TL was rapidly attained with few dose adaptations after LCPT initiation in de novo liver transplant patients. Liver function rapidly improved, whereas kidney function remained normal. LCPT was well-tolerated in this population. Full article
(This article belongs to the Special Issue Liver Transplantation: Current Challenges and New Perspectives)
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17 pages, 839 KiB  
Article
Planned Extracorporeal Life Support Employment during Liver Transplantation: The Potential of ECMO and CRRT as Preventive Therapies—Case Reports and Literature Review
by Cristiana Laici, Amedeo Bianchini, Noemi Miglionico, Niccolò Bambagiotti, Giovanni Vitale, Guido Fallani, Matteo Ravaioli and Antonio Siniscalchi
J. Clin. Med. 2023, 12(3), 1239; https://doi.org/10.3390/jcm12031239 - 03 Feb 2023
Cited by 2 | Viewed by 2237
Abstract
Liver Transplantation (LT) has become the gold standard treatment for End-Stage Liver Disease (ESLD). One of the main strategies to manage life-threatening complications, such as cardio-respiratory failure, is Extracorporeal Membrane Oxygenation (ECMO) in the peri-transplantation period, with different configurations of the technique and [...] Read more.
Liver Transplantation (LT) has become the gold standard treatment for End-Stage Liver Disease (ESLD). One of the main strategies to manage life-threatening complications, such as cardio-respiratory failure, is Extracorporeal Membrane Oxygenation (ECMO) in the peri-transplantation period, with different configurations of the technique and in combination with other extracorporeal care devices such as Continuous Renal Replacement Therapy (CRRT). This retrospective study includes three clinical cases of planned ECMO support strategies in LT and evaluates their application compared with current literature exploring PubMed/Medline. The three LT supported with ECMO and CRRT were performed at IRCCS Polyclinic S. Orsola-Malpighi, Bologna. All three cases of patients with compromised organ function analysed produced positive outcomes. The planned use of ECMO and CRRT support in peri-transplantation has allowed the patients to overcome contraindications and successfully undergo LT. In recent years, only a few reports have documented successful LT outcomes performed with intraoperative ECMO in critically ESLD patients. However, the management of LT with ECMO and/or CRRT assistance is an emerging challenge, with the need for more published evidence on this topic to guide treatment choices in patients with severe, acute and reversible respiratory and cardiovascular failure after LT. Full article
(This article belongs to the Special Issue Liver Transplantation: Current Challenges and New Perspectives)
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Review

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17 pages, 508 KiB  
Review
New Developments and Challenges in Liver Transplantation
by Amjad Khalil, Alberto Quaglia, Pierre Gélat, Nader Saffari, Hassan Rashidi and Brian Davidson
J. Clin. Med. 2023, 12(17), 5586; https://doi.org/10.3390/jcm12175586 - 27 Aug 2023
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Abstract
Liver disease is increasing in incidence and is the third most common cause of premature death in the United Kingdom and fourth in the United States. Liver disease accounts for 2 million deaths globally each year. Three-quarters of patients with liver disease are [...] Read more.
Liver disease is increasing in incidence and is the third most common cause of premature death in the United Kingdom and fourth in the United States. Liver disease accounts for 2 million deaths globally each year. Three-quarters of patients with liver disease are diagnosed at a late stage, with liver transplantation as the only definitive treatment. Thomas E. Starzl performed the first human liver transplant 60 years ago. It has since become an established treatment for end-stage liver disease, both acute and chronic, including metabolic diseases and primary and, at present piloting, secondary liver cancer. Advances in surgical and anaesthetic techniques, refined indications and contra-indications to transplantation, improved donor selection, immunosuppression and prognostic scoring have allowed the outcomes of liver transplantation to improve year on year. However, there are many limitations to liver transplantation. This review describes the milestones that have occurred in the development of liver transplantation, the current limitations and the ongoing research aimed at overcoming these challenges. Full article
(This article belongs to the Special Issue Liver Transplantation: Current Challenges and New Perspectives)
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Other

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16 pages, 467 KiB  
Systematic Review
Normothermic Ex Vivo Machine Perfusion for Liver Transplantation: A Systematic Review of Progress in Humans
by Charles W. G. Risbey and Carlo Pulitano
J. Clin. Med. 2023, 12(11), 3718; https://doi.org/10.3390/jcm12113718 - 28 May 2023
Cited by 3 | Viewed by 1283
Abstract
Background: Liver transplantation is a lifesaving procedure for patients with end-stage liver disease (ESLD). However, many patients never receive a transplant due to insufficient donor supply. Historically, organs have been preserved using static cold storage (SCS). However, recently, ex vivo normothermic machine perfusion [...] Read more.
Background: Liver transplantation is a lifesaving procedure for patients with end-stage liver disease (ESLD). However, many patients never receive a transplant due to insufficient donor supply. Historically, organs have been preserved using static cold storage (SCS). However, recently, ex vivo normothermic machine perfusion (NMP) has emerged as an alternative technique. This paper aims to investigate the clinical progress of NMP in humans. Methods: Papers evaluating the clinical outcomes of NMP for liver transplantation in humans were included. Lab-based studies, case reports, and papers utilizing animal models were excluded. Literature searches of MEDLINE and SCOPUS were conducted. The revised Cochrane risk-of-bias tool for randomised trials (RoB 2) and the risk of bias in nonrandomised studies for interventions (ROBINS-I) tools were used. Due to the heterogeneity of the included papers, a meta-analysis was unable to be completed. Results: In total, 606 records were identified, with 25 meeting the inclusion criteria; 16 papers evaluated early allograft dysfunction (EAD) with some evidence for lower rates using NMP compared to SCS; 19 papers evaluated patient or graft survival, with no evidence to suggest superior outcomes with either NMP or SCS; 10 papers evaluated utilization of marginal and donor after circulatory death (DCD) grafts, with good evidence to suggest NMP is superior to SCS. Conclusions: There is good evidence to suggest that NMP is safe and that it likely affords clinical advantages to SCS. The weight of evidence supporting NMP is growing, and this review found the strongest evidence in support of NMP to be its capacity to increase the utilization rates of marginal and DCD allografts. Full article
(This article belongs to the Special Issue Liver Transplantation: Current Challenges and New Perspectives)
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