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Developments and Challenges in Liver Transplantation
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Developments and Challenges in Liver Transplantation

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 (30 April 2025) | Viewed by 7067

Special Issue Editor

Dr. Paolo De Simone

E-Mail Website
Guest Editor
Division of Hepatic Surgery and Liver Transplantation, University of Pisa Medical School Hospital, 56126 Pisa, Italy
Interests: liver transplantation; hepatocellular carcinoma; immunosuppression; hepatobiliary surgery; liver diseases; liver cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Liver transplantation is one of the main treatments for end-stage liver disease and has made significant progress in recent years. The introduction of new surgical techniques, immunosuppressive drugs, and organ preservation methods has improved the success and survival rates of liver transplantation. However, the problem of donor shortage still exists, and the long-term use of immunosuppressive drugs may lead to side effects and complications. In addition, postoperative care and complication management are critical to patient recovery and survival. This Special Issue will summarize improvements in liver transplantation techniques, donor shortage issues, immunosuppression and rejection, and postoperative care and complication management.

This Special Issue aims to promote scholarly communication and provide valuable information to physicians, researchers, and patients. We invite researchers working in the field of liver transplantation and related areas to submit their findings as original articles or reviews to this Special Issue.

Dr. Paolo De Simone
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • liver transplantation
  • end-stage liver disease
  • organ preservation
  • transplant rejection
  • post-transplantation
  • immunotolerance
  • perioperative care

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Published Papers (5 papers)

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Research

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9 pages, 686 KiB  
Article
Normothermic Machine Perfusion in Orphan Liver Graft Viability Assessment
by Marcin Morawski, Andriy Zhylko, Hubert Kubiszewski, Jakub Rochoń, Paweł Rykowski, Mikołaj Staszewski, Maciej Krasnodębski, Wojciech Figiel, Marek Krawczyk and Michał Grąt
J. Clin. Med. 2025, 14(3), 777; https://doi.org/10.3390/jcm14030777 - 24 Jan 2025
Cited by 1 | Viewed by 859
Abstract
Background: Liver transplantation constitutes a well-established treatment for patients with end-stage liver disease and selected hepatic malignancies. The introduction of normothermic machine perfusion (NMP) offers a platform for both extracorporeal organ maintenance and viability assessment, especially for organs with suspicious malfunction. These [...] Read more.
Background: Liver transplantation constitutes a well-established treatment for patients with end-stage liver disease and selected hepatic malignancies. The introduction of normothermic machine perfusion (NMP) offers a platform for both extracorporeal organ maintenance and viability assessment, especially for organs with suspicious malfunction. These organs, discarded by the majority of transplant centers (so-called ‘orphan livers’), may help to safely expand the donor pool thanks to pre-transplant appraisal; Methods: We identified all grafts undergoing normothermic ma-chine perfusions performed in the Department of General, Transplant, and Liver Surgery between December 2022 and August 2023. Their perfusion characteristics and immediate postoperative periods, as well as complications that occurred in the 90-day postoperative periods, were analyzed; Results: There were eight orphan liver grafts that underwent NMP in our Department. Postoperative complications occurring in patients receiving grafts after NMP did not seem associated with the procedure. One patient required laparotomy within the 90-day postoperative period due to biliary fistula and underwent bile duct stenting due to both fistula and nonanastomotic stricture. In one patient we observed the occurrence of anastomotic biliary stricture more than 90 days after LTx; Conclusions: NMP allows for the viability assessment of grafts with suspicious prepreservation malfunction. Some of these organs may help to expand the donor pool. Full article
(This article belongs to the Special Issue Developments and Challenges in Liver Transplantation)
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Review

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12 pages, 595 KiB  
Review
Frailty after Liver Transplantation: A Complex Unexplored Issue
by Filippo Gabrielli, Filippo Biagi, Alessandra Avossa, Margherita Falcini, Fabio Nascimbeni, Pietro Andreone and Stefano Gitto
J. Clin. Med. 2024, 13(15), 4537; https://doi.org/10.3390/jcm13154537 - 2 Aug 2024
Cited by 1 | Viewed by 1356
Abstract
Frailty is a multidimensional syndrome predominantly studied in the elderly, characterized by reduced resistance to stressors due to diminished physiological reserve and resilience. Advances in surgical techniques and immunosuppressive drugs have improved long-term survival rates in solid organ transplant recipients, yet the 10-year [...] Read more.
Frailty is a multidimensional syndrome predominantly studied in the elderly, characterized by reduced resistance to stressors due to diminished physiological reserve and resilience. Advances in surgical techniques and immunosuppressive drugs have improved long-term survival rates in solid organ transplant recipients, yet the 10-year survival is satisfying. However, liver transplant recipients have a noteworthy risk of developing frailty status. After liver transplant, frailty can be favored by socioeconomic, cultural, and health-related factors, leading to increased risks of hospitalization, morbidity, and mortality. Various tools for frailty assessment exist, but none are universally validated for post-transplant patients. The integration of socioeconomic and psychological factors into frailty evaluation could improve quality of life and long-term outcomes for transplant recipients. Multidisciplinary approaches, including psychosocial support, are essential for managing frailty and enhancing the overall care of transplanted patients. This narrative review aims to comprehensively address the principal frailty risk factors associated with liver transplantation. Full article
(This article belongs to the Special Issue Developments and Challenges in Liver Transplantation)
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Other

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3 pages, 158 KiB  
Comment
Comment on Gaspari et al. Blood Purification in Hepatic Dysfunction after Liver Transplant or Extensive Hepatectomy: Far from the Best-Case Scenarios. J. Clin. Med. 2024, 13, 2853
by Ivano Riva, Stefano Faenza, Antonio Siniscalchi, Elisabetta Cerutti and Giandomenico Luigi Biancofiore
J. Clin. Med. 2025, 14(3), 716; https://doi.org/10.3390/jcm14030716 - 23 Jan 2025
Cited by 1 | Viewed by 466
Abstract
We read with interest the paper entitled Case Report Blood Purification in Hepatic Dysfunction after Liver Transplant or Extensive Hepatectomy: Far from the Best-Case Scenarios, which was recently published in the Journal of Clinical Medicine [...] Full article
(This article belongs to the Special Issue Developments and Challenges in Liver Transplantation)
14 pages, 1845 KiB  
Case Report
Utilization of Immunotherapy as a Neoadjuvant Therapy for Liver Transplant Recipients with Hepatocellular Carcinoma
by Maen Abdelrahim, Abdullah Esmail, Mukul K. Divatia, Jiaqiong Xu, Sudha Kodali, David W. Victor, Elizabeth Brombosz, Ashton A. Connor, Ashish Saharia, Ahmed Elaileh, Ahmed O. Kaseb and Rafik Mark Ghobrial
J. Clin. Med. 2024, 13(11), 3068; https://doi.org/10.3390/jcm13113068 - 24 May 2024
Cited by 9 | Viewed by 2277
Abstract
Background: Hepatocellular carcinoma (HCC) is widely recognized as the predominant type of primary liver malignancy. Orthotopic liver transplantation (OLT) has emerged as a highly effective treatment option for unresectable HCC. Immunotherapies as neoadjuvant options are now being actively investigated in the transplant oncology [...] Read more.
Background: Hepatocellular carcinoma (HCC) is widely recognized as the predominant type of primary liver malignancy. Orthotopic liver transplantation (OLT) has emerged as a highly effective treatment option for unresectable HCC. Immunotherapies as neoadjuvant options are now being actively investigated in the transplant oncology era to enhance outcomes in patients with HCC. Here, we report our experience with patients with HCC who had received Immune Checkpoint Inhibitors (ICPI) prior to curative OLT. Methods: This was a retrospective cohort that included patients with HCC who received ICPI prior to OLT at a single institution from January 2019 to August 2023. Graft rejection was assessed and reported along with the type of ICPI, malignancy treated, and the timing of ICPI in association with OLT. Results: During this cohort period, six patients with HCC underwent OLT after neoadjuvant ICPI. All patients were male with a median age of 61 (interquartile range: 59–64) years at OLT. Etiology associated with HCC was viral (N = 4) or Non-alcoholic steatohepatitis, NASH (N = 2). Tumor focality was multifocal (N = 4) and unifocal (N = 2). Lymphovascular invasion was identified in four patients. No perineural invasion was identified in any of the patients. All patients received ICPI including atezolizumab/bevacizumab (N = 4), nivolumab/ipilimumab (N = 1), and nivolumab as monotherapy (N = 1). All patients received either single or combined liver-directed/locoregional therapy, including transarterial chemoembolization (TACE), Yttrium-90 (Y90), stereotactic body radiotherapy (SBRT), and radiofrequency ablation (RFA). The median washout period was 5 months. All patients responded to ICPI and achieved a safe and successful OLT. All patients received tacrolimus plus mycophenolate as immunosuppressant (IS) therapy post-OLT and one patient received prednisone as additional IS. No patient had clinical evidence of rejection. Conclusions: This cohort emphasizes the success of tumor downstaging by ICPI for OLT when employed as the neoadjuvant therapy strategy. In addition, this study illustrated the importance of timing for the administration of ICPI before OLT. Given the lack of conclusive evidence in this therapeutic area, we believe that our study lays the groundwork for prospective trials to further examine the impact of ICPI prior to OLT. Full article
(This article belongs to the Special Issue Developments and Challenges in Liver Transplantation)
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11 pages, 1133 KiB  
Case Report
Blood Purification in Hepatic Dysfunction after Liver Transplant or Extensive Hepatectomy: Far from the Best-Case Scenarios
by Rita Gaspari, Paola Aceto, Giorgia Spinazzola, Edoardo Piervincenzi, Maurizio Chioffi, Felice Giuliante, Massimo Antonelli and Alfonso Wolfango Avolio
J. Clin. Med. 2024, 13(10), 2853; https://doi.org/10.3390/jcm13102853 - 12 May 2024
Cited by 4 | Viewed by 1243
Abstract
Background: Hepatic dysfunction (HD) after liver transplantation (LT) or extended hepatic resection (EHR) is associated with graft failure and high short-term mortality. We evaluated the safety and depurative efficacy of CytoSorb® in these settings. The primary endpoint was the change in serum [...] Read more.
Background: Hepatic dysfunction (HD) after liver transplantation (LT) or extended hepatic resection (EHR) is associated with graft failure and high short-term mortality. We evaluated the safety and depurative efficacy of CytoSorb® in these settings. The primary endpoint was the change in serum total bilirubin at the end of the treatment compared to the baseline value. The secondary endpoint was to evaluate the trend of serum total bilirubin and coagulation parameters up to 72 h after discontinuation of CytoSorb®. The effects of CytoSorb® therapy on the degree of hepatic encephalopathy (HE), Sequential Organ Failure Assessment (SOFA), and Model for End-Stage Liver Disease (MELD) scores as well as the hemodynamic status compared to baseline were also assessed. Methods: Adult patients with a serum total bilirubin level > 10 mg/dL admitted to the Intensive Care Unit were included. Exclusion criteria were hemodynamic instability, postoperative bleeding and platelet count < 20,000/mm3. Results: Seven patients were treated. Serum total bilirubin was significantly reduced at the end of treatment. However, seventy-two hours after the discontinuation of extracorporeal therapy, bilirubin levels returned to baseline levels in four patients. A decrease in platelet count was found during therapy, and platelet transfusion was required in six cases. A significant increase in D-dimer at the end of treatment was detected. HE degree, SOFA and MELD scores remained stable, while a deterioration in hemodynamic status was observed in two cases. Conclusions: Our preliminary findings did not show the possible benefits of CytoSorb® in rebalancing clinical and laboratory parameters in patients with HD after LT or EHR. Full article
(This article belongs to the Special Issue Developments and Challenges in Liver Transplantation)
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