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Recent Advances in Liver Transplantation and Adjacent Therapies

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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 2023) | Viewed by 11850

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Special Issue Editor

Dr. Markus Schoenberg

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Guest Editor

1. Medical Faculty, Ludwig-Maximilian-University Munich, 80539 Munich, Germany
2. Medical Center Gollierplatz, 80539 Munich, Germany
Interests: liver transplantation; liver resection; colorectal metastases

Special Issue Information

Dear Colleagues,

Current advances in liver transplantation with well-established transplant programs all around the world have given us the opportunity, not only to improve outcomes and increase organ availability, but also to continue to push boundaries. It also helps us to deal with still existing challenges in this field. This includes novel techniques to improve organ quality; more insightful surgical techniques; expansion of the indications for liver transplant; decreasing the risk of complications often leading to re-transplantation, rejection, and disease recurrence; as well as understanding the underlying diseases causing liver failure.

Furthermore ex situ and in situ machine perfusion of the donor livers has opened multiple possibilities, not only to assess donor graft quality but to apply different therapeutic strategies to rescue or restore liver damage. The increasing understanding in transplant surgery has led to a better management when dealing with spontaneous porto-systemic shunts, splenic artery steal syndromes, or outflow obstruction. However, there is still room for improvement when calculating predictions and preventing complications. This is especially true for cases involving living donor liver transplants, auxiliary liver transplantation, or even multiorgan transplantation.

Demographic changes worldwide have changed the indications for liver transplantation, not only to non-alcoholic steatohepatitis, which requires an additional multidisciplinary approach to prevent recurrence of the disease, but also to expand the criteria in hepatocellular carcinoma beyond mere morphometric requirements. For hepatocellular carcinoma in particular, an improved surgical risk appraisal could reduce the burden on the waiting list and treat more patients by resection. Additionally, novel indications for liver transplantation such as colorectal metastasis, neuroendocrine tumors and cholangiocarcinoma have been tested with interesting and diverse results. Other indications include diseases such as sickle cell disease and methylmalonic acidaemia, among others. With widened indications, the pressure on the donor pool is mounting and the need for an allocation system that takes urgency and utility into considerations is more urgent than ever.

Despite the excellent immunosuppressive strategies, rejection and side effects of this medication are still a challenge that compromises patient outcome. Multiple efforts are being made towards tolerogenic strategies and novel in part locally immunosuppressive therapies to prevent graft loss and improve long-term outcomes.

In this Special Issue, we invite researchers to submit high-quality original papers or reviews on new insights about the most recent advances in liver transplantation and adjacent therapies, including emerging indications; changes in allocation, medical, surgical, and quality management to increase short- and long-term survival; and new therapeutics to improve donor liver survival.

Dr. Markus Schoenberg
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
machine learning
non alcoholic steatohepatitis
cholangiocarcinoma
colorectal liver metastases
neuroendocrine liver metastases
hepatocellular carcinoma
normothermic regional perfusion
extracorporeal machine preservation
auxiliary liver transplantation
immunosuppression
quality management

Published Papers (6 papers)

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Research

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18 pages, 1900 KiB

Open AccessArticle

Ileal Bile Acid Transporter Blockers for Cholestatic Liver Disease in Pediatric Patients with Alagille Syndrome: A Systematic Review and Meta-Analysis

by Hafiza Sidra tul Muntaha, Mubashar Munir, Syeda Haleema Sajid, Zouina Sarfraz, Azza Sarfraz, Karla Robles-Velasco, Muzna Sarfraz, Miguel Felix and Ivan Cherrez-Ojeda

J. Clin. Med. 2022, 11(24), 7526; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11247526 - 19 Dec 2022

Cited by 3 | Viewed by 2059

Abstract

Alagille syndrome (ALGS) is a rare, debilitating inheritable disease that is associated with refractory pruritus due to chronic cholestasis. The following systemic review and meta-analysis presents the latest evidence for ileal bile acid transport (IBAT) blockers in AGLS patients in order to improve their efficacy. This study adhered to PRISMA 2020 Statement guidelines. A systematic search of PubMed/MEDLINE, Web of Science, Scopus, and the Cochrane library was conducted from inception until 23 October 2022. A combination of the following keywords was used: Alagille syndrome, therapeutics, treatment, therapy. Meta-analytical outcomes included effect directions of end-line changes in serum bile acids (sBAs), Itch Scale scores (ItchRO), Multidimensional Fatigue Scale scores, pediatric quality of life (QL), alanine aminotransferase (ALT), and total bilirubin. A total of 94 patients across four trials were enrolled and received maralixibat, odevixibat, or a placebo. There was a significant reduction in ItchRO scores by 1.8 points, as well as in sBAs by 75.8 μmol/L. Both the Multidimensional Fatigue Scale and Pediatric QL scale were also improved by 11.4 and 8.3 points, respectively. However, ALT levels were raised by 40 U/L. The efficacy of IBAT inhibitors across current trials was noted. Future trials may focus on the optimization of dosing regimens, considering gastrointestinal side effects and drug-induced ALT elevation in AGLS patients. Full article

(This article belongs to the Special Issue Recent Advances in Liver Transplantation and Adjacent Therapies)

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13 pages, 1019 KiB

Open AccessArticle

Hypothermic Oxygenated Machine Perfusion (HOPE) Prior to Liver Transplantation Mitigates Post-Reperfusion Syndrome and Perioperative Electrolyte Shifts

by Fabian Horné, Moritz Drefs, Malte Joachim Schirren, Dominik Thomas Koch, Ganildo Cepele, Severin Johannes Jacobi, Elnaz Payani, Nikolaus Börner, Jens Werner, Markus Otto Guba and Dionysios Koliogiannis

J. Clin. Med. 2022, 11(24), 7381; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11247381 - 12 Dec 2022

Cited by 5 | Viewed by 1275

Abstract

(1) Background: Post-reperfusion syndrome (PRS) and electrolyte shifts (ES) represent considerable challenges during liver transplantation (LT) being associated with significant morbidity. We aimed to investigate the impact of hypothermic oxygenated machine perfusion (HOPE) on PRS and ES in LT. (2) Methods: In this retrospective study, we compared intraoperative parameters of 100 LTs, with 50 HOPE preconditioned liver grafts and 50 grafts stored in static cold storage (SCS). During reperfusion phase, prospectively registered serum parameters and vasopressor administration were analyzed. (3) Results: Twelve percent of patients developed PRS in the HOPE cohort vs. 42% in the SCS group (p = 0.0013). Total vasopressor demand in the first hour after reperfusion was lower after HOPE pretreatment, with reduced usage of norepinephrine (−26%; p = 0.122) and significant reduction of epinephrine consumption (−52%; p = 0.018). Serum potassium concentration dropped by a mean of 14.1% in transplantations after HOPE, compared to a slight decrease of 1% (p < 0.001) after SCS. The overall incidence of early allograft dysfunction (EAD) was reduced by 44% in the HOPE group (p = 0.04). (4) Conclusions: Pre-transplant graft preconditioning with HOPE results in higher hemodynamic stability during reperfusion and lower incidence of PRS and EAD. HOPE has the potential to mitigate ES by preventing hyperpotassemic complications that need to be addressed in LT with HOPE-pre-treated grafts. Full article

(This article belongs to the Special Issue Recent Advances in Liver Transplantation and Adjacent Therapies)

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8 pages, 527 KiB

Open AccessArticle

A Novel Deep Learning Model as a Donor–Recipient Matching Tool to Predict Survival after Liver Transplantation

by Nikolaus Börner, Markus B. Schoenberg, Philipp Pöschke, Christian Heiliger, Sven Jacob, Dominik Koch, Benedikt Pöllmann, Moritz Drefs, Dionysios Koliogiannis, Christian Böhm, Konrad W. Karcz, Jens Werner and Markus Guba

J. Clin. Med. 2022, 11(21), 6422; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11216422 - 29 Oct 2022

Cited by 2 | Viewed by 1705

Abstract

Background: The “digital era” in the field of medicine is the new “here and now”. Artificial intelligence has entered many fields of medicine and is recently emerging in the field of organ transplantation. Solid organs remain a scarce resource. Being able to predict the outcome after liver transplantation promises to solve one of the long-standing problems within organ transplantation. What is the perfect donor recipient match? Within this work we developed and validated a novel deep-learning-based donor–recipient allocation system for liver transplantation. Method: In this study we used data collected from all liver transplant patients between 2004 and 2019 at the university transplantation centre in Munich. We aimed to design a transparent and interpretable deep learning framework to predict the outcome after liver transplantation. An individually designed neural network was developed to meet the unique requirements of transplantation data. The metrics used to determine the model quality and its level of performance are accuracy, cross-entropy loss, and F1 score as well as AUC score. Results: A total of 529 transplantations with a total of 1058 matching donor and recipient observations were added into the database. The combined prediction of all outcome parameters was 95.8% accurate (cross-entropy loss of 0.042). The prediction of death within the hospital was 94.3% accurate (cross-entropy loss of 0.057). The overall F1 score was 0.899 on average, whereas the overall AUC score was 0.940. Conclusion: With the achieved results, the network serves as a reliable tool to predict survival. It adds new insight into the potential of deep learning to assist medical decisions. Especially in the field of transplantation, an AUC Score of 94% is very valuable. This neuronal network is unique as it utilizes transparent and easily interpretable data to predict the outcome after liver transplantation. Further validation must be performed prior to utilization in a clinical context. Full article

(This article belongs to the Special Issue Recent Advances in Liver Transplantation and Adjacent Therapies)

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12 pages, 1796 KiB

Open AccessArticle

Expansion of Double-Negative T Cells in Patients before Liver Transplantation Correlates with Post-Transplant Infections

by Hong Lei, Min Tian, Xiaogang Zhang, Xuemin Liu, Bo Wang, Rongqian Wu and Yi Lv

J. Clin. Med. 2022, 11(12), 3502; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11123502 - 17 Jun 2022

Cited by 1 | Viewed by 1393

Abstract

Liver transplantation (LTx) is currently the only effective therapy for patients with end-stage liver diseases, but post-transplant infection is a key issue for morbidity and mortality. In this study, we found that pre-transplant patients with an expansion of double-negative T (DNT) cells (CD3⁺CD4⁻CD8⁻ T cells) had an increased incidence of infections within the first 6 months after LTx. These DNT cells also negatively correlated with their CD4/CD8 ratio. Compared to patients who had no infections after LTx, these DNT cells expressed more CD25, especially in the memory compartment. The receiver operating characteristic (ROC) analysis showed that the threshold area under the ROC curve of DNT cells which could be used to distinguish LTx patients with post-transplant infections from patients without infections after LTx was 0.8353 (95% CI: 0.6591–1.000). The cut-off for the pre-LTx DNT cell level was 11.35%. Although patients with post-transplant infections had decreased levels of CD4/CD8 T cells, CD8⁺ T cells in these patients were more exhausted, with higher PD-1 expression and lower IFNγ secretion. The increased levels of DNT cells in patients with post-transplant infections were still observed 2 weeks after LTx, with higher proportions of memory DNT cells. In conclusion, increased levels of DNT cells in pre-LTx patients may be valuable for the prognosis of post-transplant infections, especially within the first 6 months after LTx. Full article

(This article belongs to the Special Issue Recent Advances in Liver Transplantation and Adjacent Therapies)

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14 pages, 1609 KiB

Open AccessArticle

Predictive Role of the D-Dimer Level in Acute Kidney Injury in Living Donor Liver Transplantation: A Retrospective Observational Cohort Study

by Jaesik Park, Sung Un Kim, Ho Joong Choi, Sang Hyun Hong and Min Suk Chae

J. Clin. Med. 2022, 11(2), 450; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11020450 - 16 Jan 2022

Cited by 7 | Viewed by 1939

Abstract

This study aimed to determine the association between serum D-dimer levels and the risk of acute kidney injury (AKI) in patients undergoing living donor liver transplantation (LDLT). Clinical data of 675 patients undergoing LDLT were retrospectively analyzed. The exclusion criteria included a history of kidney dysfunction, emergency cases, and missing data. The final study population of 617 patients was divided into the normal and high D-dimer groups (cutoff: 0.5 mg/L). After LDLT, 145 patients (23.5%) developed AKI. A high D-dimer level (>0.5 mg/L) was an independent predictor of postoperative development of AKI in the multivariate analysis when combined with diabetes mellitus [DM], platelet count, and hourly urine output. AKI was significantly higher in the high D-dimer group than in the normal D-dimer group (odds ratio [OR], 2.792; 95% confidence interval [CI], 1.227–6.353). Patients with a high D-dimer exhibited a higher incidence of early allograft dysfunction, longer intensive care unit stay, and a higher mortality rate. These results could improve the risk stratification of postoperative AKI development by encouraging the determination of preoperative D-dimer levels in patients undergoing LDLT. Full article

(This article belongs to the Special Issue Recent Advances in Liver Transplantation and Adjacent Therapies)

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Other

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14 pages, 1799 KiB

Open AccessSystematic Review

Robotic Living Donor Right Hepatectomy: A Systematic Review and Meta-Analysis

by Eddy P. Lincango Naranjo, Estefany Garces-Delgado, Timo Siepmann, Lutz Mirow, Paola Solis-Pazmino, Harold Alexander-Leon, Gabriela Restrepo-Rodas, Rafael Mancero-Montalvo, Cristina J. Ponce, Ramiro Cadena-Semanate, Ronnal Vargas-Cordova, Glenda Herrera-Cevallos, Sebastian Vallejo, Carolina Liu-Sanchez, Larry J. Prokop, Ioannis A. Ziogas, Michail G. Vailas, Alfredo D. Guerron, Brendan C. Visser, Oscar J. Ponce, Andrew S. Barbas and Dimitrios Moris Show full author list Hide full author list

J. Clin. Med. 2022, 11(9), 2603; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11092603 - 05 May 2022

Cited by 7 | Viewed by 2550

Abstract

The introduction of robotics in living donor liver transplantation has been revolutionary. We aimed to examine the safety of robotic living donor right hepatectomy (RLDRH) compared to open (ODRH) and laparoscopic (LADRH) approaches. A systematic review was carried out in Medline and six additional databases following PRISMA guidelines. Data on morbidity, postoperative liver function, and pain in donors and recipients were extracted from studies comparing RLDRH, ODRH, and LADRH published up to September 2020; PROSPERO (CRD42020214313). Dichotomous variables were pooled as risk ratios and continuous variables as weighted mean differences. Four studies with a total of 517 patients were included. In living donors, the postoperative total bilirubin level (MD: −0.7 95%CI −1.0, −0.4), length of hospital stay (MD: −0.8 95%CI −1.4, −0.3), Clavien–Dindo complications I–II (RR: 0.5 95%CI 0.2, 0.9), and pain score at day > 3 (MD: −0.6 95%CI −1.6, 0.4) were lower following RLDRH compared to ODRH. Furthermore, the pain score at day > 3 (MD: −0.4 95%CI −0.8, −0.09) was lower after RLDRH when compared to LADRH. In recipients, the postoperative AST level was lower (MD: −0.5 95%CI −0.9, −0.1) following RLDRH compared to ODRH. Moreover, the length of stay (MD: −6.4 95%CI −11.3, −1.5) was lower after RLDRH when compared to LADRH. In summary, we identified low- to unclear-quality evidence that RLDRH seems to be safe and feasible for adult living donor liver transplantation compared to the conventional approaches. No postoperative deaths were reported. Full article

(This article belongs to the Special Issue Recent Advances in Liver Transplantation and Adjacent Therapies)

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