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Challenges in Liver Transplantation: Extended Criteria Donors
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Challenges in Liver Transplantation: Extended Criteria Donors

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 May 2022) | Viewed by 18842

Special Issue Editors

Dr. Parissa Tabrizian

E-Mail Website
Guest Editor
Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Interests: hepatocellular carcinoma; cholangiocarcinoma; liver resection; liver transplantation; outcome
Dr. Miriam Cortes Cerisuelo

E-Mail Website
Guest Editor
Institute of Liver Studies, 3rd Floor Cheyne Wing, King's College Hospita, Denmark Hill, London SE5 9RS, UK
Interests: transplant surgery; machine perfusion; pediatric malignancies; DCD; immunogenicity

Special Issue Information

Dear Colleagues,

As many of you already know, despite an increase in the number of liver transplantations, the mortality on the waiting list remains 10%. The demand for donor livers continues to exceed supply worldwide. Alternative solutions, in order to increase the donor pool, are the use of marginal donors including elderly donors, steatotic grafts, non-heart beating donors, and hepatitis C virus-positive grafts. These marginal donors have been discouraged by transplant recipients due to reports of graft failure, poor function, and disease transmission. In addition, the advent of liver machine perfusion has dramatically impacted the transplant community worldwide and shown significantly lower hepatocyte injury.

With this Special Issue, we hope to focus on recent advances in the use of marginal donors and encourage their utilization to help increase the donor pool.

Dr. Parissa Tabrizian
Dr. Miriam Cortes-Cerisuelo
Guest Editor

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Keywords

  • Extended criteria donor
  • Liver transplantation
  • Liver machine perfusion
  • Outcome

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Published Papers (7 papers)

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Research

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13 pages, 2399 KiB  
Article
Liver Transplantation for Biliary Atresia in Adulthood: Single-Centre Surgical Experience
by Miriam Cortes-Cerisuelo, Christina Boumpoureka, Noel Cassar, Deepak Joshi, Marianne Samyn, Michael Heneghan, Krishna Menon, Andreas Prachalias, Parthi Srinivasan, Wayel Jassem, Hector Vilca-Melendez, Anil Dhawan and Nigel D. Heaton
J. Clin. Med. 2021, 10(21), 4969; https://doi.org/10.3390/jcm10214969 - 26 Oct 2021
Cited by 8 | Viewed by 2335
Abstract
Background: Biliary atresia (BA) is the most common indicator for liver transplant (LT) in children, however, approximately 22% will reach adulthood with their native liver, and of these, half will require transplantation later in life. The aim of this study was to analyse [...] Read more.
Background: Biliary atresia (BA) is the most common indicator for liver transplant (LT) in children, however, approximately 22% will reach adulthood with their native liver, and of these, half will require transplantation later in life. The aim of this study was to analyse the surgical challenges and outcomes of patients with BA undergoing LT in adulthood. Methods: Patients with BA requiring LT at the age of 16 or older in our unit between 1989 and 2020 were included. Pretransplant, perioperative variables and outcomes were analysed. Pretransplant imaging was reviewed to assess liver appearance, spontaneous visceral portosystemic shunting (SPSS), splenomegaly, splenic artery (SA) size, and aneurysms. Results: Thirty-four patients who underwent LT for BA fulfilled the inclusion criteria, at a median age of 24 years. The main indicators for LT were synthetic failure and recurrent cholangitis. In total, 57.6% had significant enlargement of the SA, 21% had multiple SA aneurysm, and SPSS was present in 72.7% of the patients. Graft and patient survival at 1, 5, and 10 years was 97.1%, 91.2%, 91.2% and 100%, 94%, 94%, respectively Conclusions: Good outcomes after LT for BA in young patients can be achieved with careful donor selection and surgery to minimise the risk of complications. Identification of anatomical variants and shunting are helpful in guiding attitude at the time of transplant. Full article
(This article belongs to the Special Issue Challenges in Liver Transplantation: Extended Criteria Donors)
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13 pages, 979 KiB  
Article
Tailored Prediction Model of Survival after Liver Transplantation for Hepatocellular Carcinoma
by Indah Jamtani, Kwang-Woong Lee, Yunhee Choi, YoungRok Choi, Jeong-Moo Lee, Eui-Soo Han, Kwangpyo Hong, Gyu-Seong Choi, Jong Man Kim, Nam-Joon Yi, Suk Kyun Hong, Jeik Byun, Su Young Hong, Sanggyeun Suh, Jae-Won Joh and Kyung-Suk Suh
J. Clin. Med. 2021, 10(13), 2869; https://doi.org/10.3390/jcm10132869 - 28 Jun 2021
Cited by 1 | Viewed by 2264
Abstract
This study aimed to create a tailored prediction model of hepatocellular carcinoma (HCC)-specific survival after transplantation based on pre-transplant parameters. Data collected from June 2006 to July 2018 were used as a derivation dataset and analyzed to create an HCC-specific survival prediction model [...] Read more.
This study aimed to create a tailored prediction model of hepatocellular carcinoma (HCC)-specific survival after transplantation based on pre-transplant parameters. Data collected from June 2006 to July 2018 were used as a derivation dataset and analyzed to create an HCC-specific survival prediction model by combining significant risk factors. Separate data were collected from January 2014 to June 2018 for validation. The prediction model was validated internally and externally. The data were divided into three groups based on risk scores derived from the hazard ratio. A combination of patient demographic, laboratory, radiological data, and tumor-specific characteristics that showed a good prediction of HCC-specific death at a specific time (t) were chosen. Internal and external validations with Uno’s C-index were 0.79 and 0.75 (95% confidence interval (CI) 0.65–0.86), respectively. The predicted survival after liver transplantation for HCC (SALT) at a time “t” was calculated using the formula: [1 − (HCC-specific death(t’))] × 100. The 5-year HCC-specific death and recurrence rates in the low-risk group were 2% and 5%; the intermediate-risk group was 12% and 14%, and in the high-risk group were 71% and 82%. Our HCC-specific survival predictor named “SALT calculator” could provide accurate information about expected survival tailored for patients undergoing transplantation for HCC. Full article
(This article belongs to the Special Issue Challenges in Liver Transplantation: Extended Criteria Donors)
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15 pages, 1464 KiB  
Article
Perioperative ABO Blood Group Isoagglutinin Titer and the Risk of Acute Kidney Injury after ABO-Incompatible Living Donor Liver Transplantation
by Hyeyeon Cho, Jinyoung Bae, Hyun-Kyu Yoon, Ho-Jin Lee, Seong-Mi Yang, Suk Hyung Choe, Chul-Woo Jung, Kyung-Suk Suh and Won Ho Kim
J. Clin. Med. 2021, 10(8), 1679; https://doi.org/10.3390/jcm10081679 - 14 Apr 2021
Cited by 3 | Viewed by 2317
Abstract
For ABO-incompatible liver transplantation (ABO-i LT), therapeutic plasma exchange (TPE) is performed preoperatively to reduce the isoagglutinin titer of anti-ABO blood type antibodies. We evaluated whether perioperative high isoagglutinin titer is associated with postoperative risk of acute kidney injury (AKI). In 130 cases [...] Read more.
For ABO-incompatible liver transplantation (ABO-i LT), therapeutic plasma exchange (TPE) is performed preoperatively to reduce the isoagglutinin titer of anti-ABO blood type antibodies. We evaluated whether perioperative high isoagglutinin titer is associated with postoperative risk of acute kidney injury (AKI). In 130 cases of ABO-i LT, we collected immunoglobulin (Ig) G and Ig M isoagglutinin titers of baseline, pre-LT, and postoperative peak values. These values were compared between the patients with and without postoperative AKI. Multivariable logistic regression analysis was used to evaluate the association between perioperative isoagglutinin titers and postoperative AKI. Clinical and graft-related outcomes were compared between high and low baseline and postoperative peak isoagglutinin groups. The incidence of AKI was 42.3%. Preoperative baseline and postoperative peak isoagglutinin titers of both Ig M and Ig G were significantly higher in the patients with AKI than those without AKI. Multivariable logistic regression analysis showed that preoperative baseline and postoperative peak Ig M isoagglutinin titers were significantly associated with the risk of AKI (baseline: odds ratio 1.06, 95% confidence interval 1.02 to 1.09; postoperative peak: odds ratio 1.08, 95% confidence interval 1.04 to 1.13). Cubic spline function curves show a positive relationship between the baseline and postoperative peak isoagglutinin titers and the risk of AKI. Clinical outcomes other than AKI were not significantly different according to the baseline and postoperative peak isoagglutinin titers. Preoperative high initial and postoperative peak Ig M isoagglutinin titers were significantly associated with the development of AKI. As the causal relationship between high isoagglutinin titers and risk of AKI is unclear, the high baseline and postoperative isoagglutinin titers could be used simply as a warning sign for the risk of AKI after liver transplantation. Full article
(This article belongs to the Special Issue Challenges in Liver Transplantation: Extended Criteria Donors)
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10 pages, 1868 KiB  
Article
Pre-Liver Transplant ROTEM™ Clot Lysis Index Is Associated with 30-Day Mortality, But Is Not a Measure for Fibrinolysis
by Matthias Hartmann, Bogdan Craciun, Andreas Paul, Thorsten Brenner and Fuat H. Saner
J. Clin. Med. 2020, 9(10), 3298; https://doi.org/10.3390/jcm9103298 - 14 Oct 2020
Cited by 7 | Viewed by 2145
Abstract
Complex alterations of the coagulation system in end stage liver disease lead to an increased risk of bleeding and mortality. In the present study, we investigated; 1. the association of pre-liver transplant rotational thrombelastometry (ROTEM™) variables with bleeding as well as 30-day-mortality and [...] Read more.
Complex alterations of the coagulation system in end stage liver disease lead to an increased risk of bleeding and mortality. In the present study, we investigated; 1. the association of pre-liver transplant rotational thrombelastometry (ROTEM™) variables with bleeding as well as 30-day-mortality and 2. the underlying pathophysiology. After approval from the local ethics committee, rotational thrombelastometry variables, conventional laboratory coagulation values, MELD score (model of end-stage liver disease), red blood cell loss, blood product use, coagulation factors, underlying disease, and demographic data were retrospectively analysed. Pre-transplant thrombelastometry clot lysis index (CLI) and MELD were the only variables associated with mortality, bleeding and blood product use, respectively. Mortality was 4.2%, when CLI was <85%, and increased to 25.7% when the CLI was >95%. Multivariate analysis including CLI and MELD score identified the CLI as an independent and the best predictor of 30-day-mortality. Interestingly, the inhibition of fibrinolysis did neither affect CLI nor the association of the variable with mortality. Thus, fibrinolysis can be excluded as the reason for low CLI values. In conclusion, low CLI values measured before the beginning of liver transplantation are associated with reduced bleeding and mortality, but do not indicate fibrinolysis. Full article
(This article belongs to the Special Issue Challenges in Liver Transplantation: Extended Criteria Donors)
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Review

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32 pages, 2226 KiB  
Review
Machine Perfusion for Extended Criteria Donor Livers: What Challenges Remain?
by Jeannette Widmer, Janina Eden, Mauricio Flores Carvalho, Philipp Dutkowski and Andrea Schlegel
J. Clin. Med. 2022, 11(17), 5218; https://doi.org/10.3390/jcm11175218 - 3 Sep 2022
Cited by 20 | Viewed by 3191
Abstract
Based on the renaissance of dynamic preservation techniques, extended criteria donor (ECD) livers reclaimed a valuable eligibility in the transplantable organ pool. Being more vulnerable to ischemia, ECD livers carry an increased risk of early allograft dysfunction, primary non-function and biliary complications and, [...] Read more.
Based on the renaissance of dynamic preservation techniques, extended criteria donor (ECD) livers reclaimed a valuable eligibility in the transplantable organ pool. Being more vulnerable to ischemia, ECD livers carry an increased risk of early allograft dysfunction, primary non-function and biliary complications and, hence, unveiled the limitations of static cold storage (SCS). There is growing evidence that dynamic preservation techniques—dissimilar to SCS—mitigate reperfusion injury by reconditioning organs prior transplantation and therefore represent a useful platform to assess viability. Yet, a debate is ongoing about the advantages and disadvantages of different perfusion strategies and their best possible applications for specific categories of marginal livers, including organs from donors after circulatory death (DCD) and brain death (DBD) with extended criteria, split livers and steatotic grafts. This review critically discusses the current clinical spectrum of livers from ECD donors together with the various challenges and posttransplant outcomes in the context of standard cold storage preservation. Based on this, the potential role of machine perfusion techniques is highlighted next. Finally, future perspectives focusing on how to achieve higher utilization rates of the available donor pool are highlighted. Full article
(This article belongs to the Special Issue Challenges in Liver Transplantation: Extended Criteria Donors)
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12 pages, 537 KiB  
Review
Transplantation of Organs from Hepatitis C Virus-Positive Donors under Direct-Acting Antiviral Regimens
by Muhammad Nauman Zahid
J. Clin. Med. 2022, 11(3), 770; https://doi.org/10.3390/jcm11030770 - 31 Jan 2022
Cited by 5 | Viewed by 2616
Abstract
There is a discrepancy between the patients requiring organ transplants and the donors available to meet that demand. Many patients die every year while on the waiting list, and there is a need to bridge this gap. For many years, medical practitioners have [...] Read more.
There is a discrepancy between the patients requiring organ transplants and the donors available to meet that demand. Many patients die every year while on the waiting list, and there is a need to bridge this gap. For many years, medical practitioners have been apprehensive of using donor organs from donors who have tested positive for the Hepatitis C virus (HCV), and with good reason. HCV has been proven to be among the leading causes of liver diseases requiring liver transplants. Over the years, studies have been carried out to find a treatment for Hepatitis C. The advent of direct-acting antivirals revolutionized the medical world. These medication regimens have been proven to treat Hepatitis C in transplant patients effectively. This systematic review will examine how DAA treatments affect transplants of different organs from HCV-positive donors to HCV-negative recipients. Full article
(This article belongs to the Special Issue Challenges in Liver Transplantation: Extended Criteria Donors)
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15 pages, 409 KiB  
Review
An Update on Usage of High-Risk Donors in Liver Transplantation
by Haris Muhammad, Duha Zaffar, Aniqa Tehreem, Peng-Sheng Ting, Cem Simsek, Ilker Turan, Saleh Alqahtani, Behnam Saberi and Ahmet Gurakar
J. Clin. Med. 2022, 11(1), 215; https://doi.org/10.3390/jcm11010215 - 31 Dec 2021
Cited by 9 | Viewed by 2547
Abstract
The ideal management for end stage liver disease, acute liver failure, and hepatocellular carcinoma (HCC), within specific criteria, is liver transplantation (LT). Over the years, there has been a steady increase in the candidates listed for LT, without a corresponding increase in the [...] Read more.
The ideal management for end stage liver disease, acute liver failure, and hepatocellular carcinoma (HCC), within specific criteria, is liver transplantation (LT). Over the years, there has been a steady increase in the candidates listed for LT, without a corresponding increase in the donor pool. Therefore, due to organ shortage, it has been substantially difficult to reduce waitlist mortality among patients awaiting LT. Thus, marginal donors such as elderly donors, steatotic donors, split liver, and donors after cardiac death (DCD), which were once not commonly used, are now considered. Furthermore, it is encouraging to see the passing of Acts, such as the HIV Organ Policy Equity (HOPE) Act, enabling further research and development in utilizing HIV grafts. Subsequently, the newer antivirals have aided in successful post-transplant period, especially for hepatitis C positive grafts. However, currently, there is no standardization, and protocols are center specific in the usage of marginal donors. Therefore, studies with longer follow ups are required to standardize its use. Full article
(This article belongs to the Special Issue Challenges in Liver Transplantation: Extended Criteria Donors)
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