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Clinical Advances and Challenges in Liver Transplantation
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Clinical Advances 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 (20 February 2023) | Viewed by 10098

Special Issue Editors

Dr. Dario Lorenzin

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Guest Editor
Liver-Kidney Transplant Unit, Department of Medicine, University of Udine, 33100 Udine, Italy
Interests: liver transplantation; transplantation surgery; liver transplant surgery
Special Issues, Collections and Topics in MDPI journals
Dr. Paola Aceto

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Guest Editor
1. Dipartimento di Scienze dell'Emergenza, Anestesiologiche e della Rianimazione, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
2. Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, Rome, Italy
Interests: geriatric anaesthesia; perioperative medicine; neuroscience (pain mechanisms; cognition) postoperative cognitive disorders; monitoring of anaesthesia depth; anaesthesia for robotic surgery; tranplantation; hemodynamic monitoring
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In deceased donor liver transplantation (DDLT), the inclusion criteria for donation have progressively been expanded in recent years. Older donors, those with multiple comorbidities, donors after circulatory death (DCD), or grafts with significant steatosis have increasingly been accepted. This trend has been determined by the increasing organ demand of liver transplantation (LT) candidates, who in turn have been listed with progressively worse clinical conditions. However, low-quality graft and high-risk recipients are associated with an greater inherent risk of post-transplant morbidity, such as early allograft dysfunction and vascular and biliary complications. Furthermore, a new trend in the selection criteria of hepatocellular carcinoma (HCC) patients for LT has been developing, aiming to integrate the routinely morphologic parameters, such as tumor number and size, with more precise markers of tumor biology and patient immune function.

On the other hand, recent technology advances have developed several new diagnostic or therapeutic tools, such as immune therapy, radiomics analysis, genomic tests, and machine perfusion, with a potentially revolutionary impact on clinical practice.

Therefore, the transplant community is now asked not only to face new clinical challenges but also to integrate LT management with new technology advances, in a widely multidisciplinary approach. The present Special Issue aims at addressing these crucial clinical issues. 

Dr. Dario Lorenzin
Dr. Paola Aceto
Guest Editors

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 (LT)
  • deceased donor liver transplantation (DDLT)
  • donors after circulatory death (DCD)

Published Papers (7 papers)

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Research

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14 pages, 1164 KiB  
Article
Treatment of Non-Anastomotic Biliary Strictures after Liver Transplantation: How Effective Is Our Current Treatment Strategy?
by Florian A. Michael, Mireen Friedrich-Rust, Hans-Peter Erasmus, Christiana Graf, Olivier Ballo, Mate Knabe, Dirk Walter, Christoph D. Steup, Marcus M. Mücke, Victoria T. Mücke, Kai H. Peiffer, Esra Görgülü, Antonia Mondorf, Wolf O. Bechstein, Natalie Filmann, Stefan Zeuzem, Jörg Bojunga and Fabian Finkelmeier
J. Clin. Med. 2023, 12(10), 3491; https://doi.org/10.3390/jcm12103491 - 16 May 2023
Cited by 1 | Viewed by 1215
Abstract
Background: Non-anastomotic biliary strictures (NAS) are a common cause of morbidity and mortality after liver transplantation. Methods: All patients with NAS from 2008 to 2016 were retrospectively analyzed. The success rate and overall mortality of an ERCP-based stent program (EBSP) were the primary [...] Read more.
Background: Non-anastomotic biliary strictures (NAS) are a common cause of morbidity and mortality after liver transplantation. Methods: All patients with NAS from 2008 to 2016 were retrospectively analyzed. The success rate and overall mortality of an ERCP-based stent program (EBSP) were the primary outcomes. Results: A total of 40 (13.9%) patients with NAS were identified, of which 35 patients were further treated in an EBSP. Furthermore, 16 (46%) patients terminated EBSP successfully, and nine (26%) patients died during the program. All deaths were caused by cholangitis. Of those, one (11%) patient had an extrahepatic stricture, while the other eight patients had either intrahepatic (3, 33%) or combined extra- and intrahepatic strictures (5, 56%). Risk factors of overall mortality were age (p = 0.03), bilirubin (p < 0.0001), alanine transaminase (p = 0.006), and aspartate transaminase (p = 0.0003). The median duration of the stent program was 34 months (ITBL: 36 months; IBL: 10 months), and procedural complications were rare. Conclusions: EBSP is safe, but lengthy and successful in only about half the patients. Intrahepatic strictures were associated with an increased risk of cholangitis. Full article
(This article belongs to the Special Issue Clinical Advances and Challenges in Liver Transplantation)
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11 pages, 571 KiB  
Article
Long-Term Results of Endoscopic Metal Stenting for Biliary Anastomotic Stricture after Liver Transplantation
by Aymeric Becq, Alexis Laurent, Quentin De Roux, Cristiano Cremone, Hugo Rotkopf, Yann Le Baleur, Farida Mesli, Christophe Duvoux, Aurélien Amiot, Charlotte Gagniere, Nicolas Mongardon, Julien Calderaro, Daniele Sommacale, Alain Luciani and Iradj Sobhani
J. Clin. Med. 2023, 12(4), 1453; https://doi.org/10.3390/jcm12041453 - 11 Feb 2023
Viewed by 1489
Abstract
(1) Background: Anastomotic biliary stricture (ABS) is a well-known complication of liver transplantation which can lead to secondary biliary cirrhosis and graft dysfunction. The goal of this study was to evaluate the long-term outcomes of endoscopic metal stenting of ABS in the setting [...] Read more.
(1) Background: Anastomotic biliary stricture (ABS) is a well-known complication of liver transplantation which can lead to secondary biliary cirrhosis and graft dysfunction. The goal of this study was to evaluate the long-term outcomes of endoscopic metal stenting of ABS in the setting of deceased donor liver transplantation (DDLT). (2) Methods: Consecutive DDLT patients with endoscopic metal stenting for ABS between 2010 and 2015 were screened. Data on diagnosis, treatment and follow-up (until June 2022) were collected. The primary outcome was endoscopic treatment failure defined as the need for surgical refection. (3) Results: Among the 465 patients who underwent LT, 41 developed ABS. It was diagnosed after a mean period of 7.4 months (+/−10.6) following LT. Endoscopic treatment was technically successful in 95.1% of cases. The mean duration of endoscopic treatment was 12.8 months (+/−9.1) and 53.7% of patients completed a 1-year treatment. After a mean follow-up of 6.9 years (+/−2.3), endoscopic treatment failed in nine patients (22%) who required surgical refection. Conclusions: Endoscopic management with metal stenting of ABS after DDLT was technically successful in most cases, and half of the patients had at least one year of indwelling stent. Endoscopic treatment long-term failure rate occurred in one fifth of the patients. Full article
(This article belongs to the Special Issue Clinical Advances and Challenges in Liver Transplantation)
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14 pages, 1176 KiB  
Article
Long-Term Survival Outcomes beyond the First Year after Liver Transplantation in Pediatric Acute Liver Failure Compared with Biliary Atresia: A Large-Volume Living Donor Liver Transplantation Single-Center Study
by Sola Lee, Nam-Joon Yi, Eui Soo Han, Su young Hong, Jeong-Moo Lee, Suk Kyun Hong, YoungRok Choi, Hyun-Young Kim, Joong Kee Youn, Dayoung Ko, Jae Sung Ko, Jin Soo Moon, Seong Mi Yang, Kwang-Woong Lee and Kyung-Suk Suh
J. Clin. Med. 2022, 11(24), 7480; https://doi.org/10.3390/jcm11247480 - 16 Dec 2022
Viewed by 1580
Abstract
Pediatric acute liver failure (PALF) is a common cause of liver transplantation (LT) but showed poor post-LT outcomes. We reviewed 36 PALF patients and 120 BA patients who underwent LT in our institution. The cause of PALF was unknown in 66.7%. PALF patients [...] Read more.
Pediatric acute liver failure (PALF) is a common cause of liver transplantation (LT) but showed poor post-LT outcomes. We reviewed 36 PALF patients and 120 BA patients who underwent LT in our institution. The cause of PALF was unknown in 66.7%. PALF patients were older (6.2 vs. 2.9 years) with higher PELD scores (31.5 vs. 24.4) and shorter waitlist time (15.7 vs. 256.1 days) (p < 0.01). PALF patients showed higher rates of post-transplant renal replacement therapy (RRT) (13.9% vs. 4.2%) and hepatic artery complications (13.9% vs. 0.8%), while portal vein complications rates were lower (0% vs. 10.8%), (p < 0.05). Although PALF patients showed lower 5-year survival rates (77.8% vs. 95.0 %, p < 0.01), the 5-year survival rates of patients who lived beyond the first year were comparable (96.6% vs. 98.3%, p = 0.516). The most common cause of deaths within one year was graft failure (75.0%) in PALF patients, but infection (67.7%) in BA patients. In multivariate analysis, lower body weight, hepatic artery complications and post-transplant RRT were associated with worse survival outcomes (p < 0.05). In conclusion, physicians should be alert to monitor the immediate postoperative graft dysfunction and hepatic artery complications and patients on post-transplant RRT in order to improve survival outcomes in PALF patients. Full article
(This article belongs to the Special Issue Clinical Advances and Challenges in Liver Transplantation)
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17 pages, 3180 KiB  
Article
Impact of Tumour Biology on Outcomes of Radical Therapy for Hepatocellular Carcinoma Oligo-Recurrence after Liver Transplantation
by Kin-Pan Au, James Yan-Yue Fung, Wing-Chiu Dai, Albert Chi-Yan Chan, Chung-Mau Lo and Kenneth Siu-Ho Chok
J. Clin. Med. 2022, 11(15), 4389; https://doi.org/10.3390/jcm11154389 - 28 Jul 2022
Cited by 1 | Viewed by 1130
Abstract
It is uncertain whether tumour biology affects radical treatment for post-transplant hepatocellular carcinoma (HCC) oligo-recurrence, i.e. recurrence limited in numbers and locations amendable to radical therapy. We conducted a retrospective study on 144 patients with post-transplant HCC recurrence. Early recurrence within one year [...] Read more.
It is uncertain whether tumour biology affects radical treatment for post-transplant hepatocellular carcinoma (HCC) oligo-recurrence, i.e. recurrence limited in numbers and locations amendable to radical therapy. We conducted a retrospective study on 144 patients with post-transplant HCC recurrence. Early recurrence within one year after transplant (HR 2.53, 95% CI 1.65–3.88, p < 0.001), liver recurrence (HR 1.74, 95% CI 1.12–2.68, p = 0.01) and AFP > 200 ng/mL upon recurrence (HR 1.62, 95% CI 1.04–2.52, p = 0.03) predicted mortality following recurrence. In patients with early recurrence and liver recurrence, radical treatment was associated with improved post-recurrence survival (early recurrence: median 18.2 ± 1.5 vs. 9.2 ± 1.5 months, p < 0.001; liver recurrence: median 28.0 ± 4.5 vs. 11.6 ± 2.0, p < 0.001). In patients with AFP > 200 ng/mL, improvement in survival did not reach statistical significance (median 18.2 ± 6.5 vs. 8.8 ± 2.2 months, p = 0.13). Survival benefits associated with radical therapy were reduced in early recurrence (13.6 vs. 9.0 months) and recurrence with high AFP (15.4 vs. 9.3 months) but were similar among patients with and without liver recurrence (16.9 vs. 16.4 months). They were also diminished in patients with multiple biological risk factors (0 risk factor: 29.0 months; 1 risk factor: 19.7 months; 2–3 risk factors: 3.4 months): The survival benefit following radical therapy was superior in patients with favourable biological recurrence but was also observed in patients with poor tumour biology. Treatment decisions should be individualised considering the oncological benefits, quality of life gain and procedural morbidity. Full article
(This article belongs to the Special Issue Clinical Advances and Challenges in Liver Transplantation)
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10 pages, 852 KiB  
Article
Continuous Renal Replacement Therapy after Liver Transplantation: Peri-Operative Associated Factors and Impact on Survival
by Gennaro Martucci, Matteo Rossetti, Sergio Li Petri, Rossella Alduino, Riccardo Volpes, Giovanna Panarello, Salvatore Gruttadauria, Gaetano Burgio and Antonio Arcadipane
J. Clin. Med. 2022, 11(13), 3803; https://doi.org/10.3390/jcm11133803 - 30 Jun 2022
Cited by 2 | Viewed by 1476
Abstract
Continuous renal replacement therapy (CRRT) following orthotopic liver transplantation (OLT) is usually started for multifactorial reasons, with variable incidence among series. This paper presents a single-center retrospective observational study on the early use (within one week) of CRRT after consecutive cadaveric OLT from [...] Read more.
Continuous renal replacement therapy (CRRT) following orthotopic liver transplantation (OLT) is usually started for multifactorial reasons, with variable incidence among series. This paper presents a single-center retrospective observational study on the early use (within one week) of CRRT after consecutive cadaveric OLT from January 2008 to December 2016. Preoperative patient characteristics and intraoperative data were collected, and patients were divided into two groups (CRRT and no CRRT) to explore the factors associated with the use of CRRT. Repeated measurements of postoperative creatinine were analyzed with generalized estimating equation (GEE) models. Among 528 OLT patients, 75 (14.2%) were treated with CRRT at least once in the first week. Patients treated with CRRT showed lower survival in a Kaplan–Meier curve (log-rank p value < 0.01). Patients treated with CRRT had a more severe preoperative profile, with a significantly higher age, MELD, BUN, creatinine, and total bilirubin, as well as a longer surgery time and a higher number of transfusions of red blood cells, plasma, and platelets (all p values < 0.05). In a stepwise multiple analysis, the following characteristics remained independently associated with the use of CRRT: the MELD score OR 1.12 (95% CL: 1.07–1.16), p value < 0.001, and the preoperative value for blood urea nitrogen OR 1.016 (95% CL: 1.010–1.023), p value < 0.001. The early use of CRRT after OLT occurred at a low rate in this large cohort; however, it was associated with worse outcomes. Apart from the preoperative severity, repeated intraoperative hypotension episodes, which were likely modifiable or preventable, were associated with the increased use of CRRT and higher postoperative creatinine. Full article
(This article belongs to the Special Issue Clinical Advances and Challenges in Liver Transplantation)
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6 pages, 947 KiB  
Article
Changes in the Deceased-Donor Trend in Korea: Establishment of Regional Trauma Centers and KODA
by Jeong-Moo Lee
J. Clin. Med. 2022, 11(5), 1239; https://doi.org/10.3390/jcm11051239 - 24 Feb 2022
Cited by 2 | Viewed by 1275
Abstract
South Korea utilizes living-donor liver transplantation to overcome a shortage of deceased donors. After the Korea Organ Donation Agency (KODA) was established, many hospitals were selected to be donor-managing hospital. A nationwide regional trauma center project was carried out separately in 2015. This [...] Read more.
South Korea utilizes living-donor liver transplantation to overcome a shortage of deceased donors. After the Korea Organ Donation Agency (KODA) was established, many hospitals were selected to be donor-managing hospital. A nationwide regional trauma center project was carried out separately in 2015. This study aims to analyze how the trend of deceased-donor recruitment and donation has changed based on policy factors such as independent organ-procurement organization (IOPO) activities and establishing regional trauma centers. KONOS data from 2010–2019 were used to analyze the impacts of these policy changes. The results showed that 62 centers had 4395 deceased donors, and 3863 recipients underwent deceased-donor liver transplantation. The two most common causes of donor death are cerebrovascular events and head trauma. When the rate of deceased donors was analyzed by the early period (2010–2014) and the late period (2015–2019), 53 non-trauma centers went from an average of 29.3 cases to 31.0 cases (6.2% increase) annually. Nine regional trauma centers showed a statistically significant increase from an average of 39.8 cases to 70.3 cases (75.9% increase) annually. Based on these policies, he locations where deceased donors are identified are changing. It is necessary to communicate with regional trauma center staff to recruit more deceased donors. Full article
(This article belongs to the Special Issue Clinical Advances and Challenges in Liver Transplantation)
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Review

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15 pages, 2138 KiB  
Review
Efficacy and Safety of Prothrombin Complex Concentrates in Liver Transplantation: Evidence from Observational Studies
by Giovanni Punzo, Valeria Di Franco, Valter Perilli, Teresa Sacco, Liliana Sollazzi and Paola Aceto
J. Clin. Med. 2023, 12(11), 3749; https://doi.org/10.3390/jcm12113749 - 29 May 2023
Viewed by 1229
Abstract
The risk/benefit ratio of using prothrombin complex concentrates (PCCs) to correct coagulation defects in patients with end-stage liver disease is still unclear. The primary aim of this review was to assess the clinical effectiveness of PCCs in reducing transfusion requirements in patients undergoing [...] Read more.
The risk/benefit ratio of using prothrombin complex concentrates (PCCs) to correct coagulation defects in patients with end-stage liver disease is still unclear. The primary aim of this review was to assess the clinical effectiveness of PCCs in reducing transfusion requirements in patients undergoing liver transplantation (LT). This systematic review of non-randomized clinical trials was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The protocol was previously registered (PROSPERO:CRD42022357627). The primary outcome was the mean number of transfused units for each blood product, including red blood cells (RBCs), fresh frozen plasma, platelets, and cryoprecipitate. Secondary outcomes included the incidence of arterial thrombosis, acute kidney injury, and haemodialysis, and hospital and intensive care unit length of stay. There were 638 patients from 4 studies considered for meta-analysis. PCC use did not affect blood product transfusions. Sensitivity analysis, including only four-factor PCC, showed a significant reduction of RBC effect size (MD: 2.06; 95%CI: 1.27–2.84) with no true heterogeneity. No significant differences in secondary outcomes were detected. Preliminary evidence indicated a lack of PCC efficacy in reducing blood product transfusions during LT, but further investigation is needed. In particular, future studies should be tailored to establish if LT patients will likely benefit from four-factor PCC therapy. Full article
(This article belongs to the Special Issue Clinical Advances and Challenges in Liver Transplantation)
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