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1
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Maharjan N, Sharma D, Pradhan S, Kandel BP, Lakhey PJ, Bhandari RS. Donors' Outcome After Living Donor Liver Transplantation in a University Teaching Hospital: A Case Series. Cureus 2024; 16:e71858. [PMID: 39559631 PMCID: PMC11572684 DOI: 10.7759/cureus.71858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/18/2024] [Indexed: 11/20/2024] Open
Abstract
Background Liver transplantation is the standard treatment for end-stage liver disease. Living donor liver transplantation is more commonly performed in Asian countries as compared to the Western due to the lack of organ donation. Donor safety is the key to sustaining a liver transplant program. Thus, we aimed to evaluate the overall safety of living donors and health-related quality of life using the 12-item Short Form Health Survey (SF-12) questionnaire at our institution. Methodology We analyzed the medical records of patients who underwent donor hepatectomy at Tribhuvan University Teaching Hospital, Kathmandu, from May 31, 2019, to April 18, 2023. Demography, postoperative complications, and quality of life were analyzed. Results The mean age of the 10 live liver donors was 27.9 years. Half of them were male. One of them had a post-hepatectomy bile leak and others did not have any post-operative complications. They have good physical and mental health status after liver donation as indicated by the average physical component summary and mental component summary scores of more than 50. Conclusion The case series highlights the safety and favorable outcomes of liver donors at a low-volume liver transplant center, where stringent preoperative assessments and careful surgical techniques were employed.
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Affiliation(s)
- Narendra Maharjan
- Department of Surgical Gastroenterology, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University Teaching Hospital, Kathmandu, NPL
| | - Deepak Sharma
- Department of Surgical Gastroenterology, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University Teaching Hospital, Kathmandu, NPL
| | - Sumita Pradhan
- Department of Surgical Gastroenterology, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University Teaching Hospital, Kathmandu, NPL
| | - Bishnu P Kandel
- Department of Surgical Gastroenterology, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University Teaching Hospital, Kathmandu, NPL
| | - Paleswan Joshi Lakhey
- Department of Surgical Gastroenterology, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University Teaching Hospital, Kathmandu, NPL
| | - Ramesh S Bhandari
- Department of Surgical Gastroenterology, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University Teaching Hospital, Kathmandu, NPL
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2
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Alnagar AM, Hajibandeh S, Hajibandeh S, Hakeem AR, Dasari BV. Impact of Donor Obesity on Graft and Recipient Survival Outcomes After Liver Transplantation: A Systematic Review and Meta-analysis. Transplant Direct 2024; 10:e1656. [PMID: 39220221 PMCID: PMC11365672 DOI: 10.1097/txd.0000000000001656] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Revised: 03/17/2024] [Accepted: 03/26/2024] [Indexed: 09/04/2024] Open
Abstract
Background The effect of donor body mass index (BMI) on liver transplantation (LT) outcomes remains unclear. Methods A systematic search of the MEDLINE, CENTRAL, Web of Science, and bibliographic reference lists was conducted. All comparative studies evaluating the outcomes of LT in obese (BMI > 30 kg/m2) and nonobese donors (BMI < 30 kg/m2) were included, and their risk of bias was assessed using the ROBINS-I assessment tool. Patient and graft survival, acute rejection, and graft failure requiring retransplantation were evaluated as outcome parameters. A random-effects model was used for outcome synthesis. Results We included 6 comparative studies reporting a total of 5071 liver transplant recipients from 708 obese and 4363 nonobese donors. There was no significant difference in 1-y (89.1% versus 84.0%, odds ratio [OR] 1.58; 95% CI 0.63-3.94, P = 0.33), 5-y (74.2%% versus 73.5%, OR 1.12; 95% CI 0.45-2.80, P = 0.81) graft survival, and 1-y (87.1% versus 90.3%, OR 0.71; 95% CI 0.43-1.15, P = 0.17) and 5-y (64.5% versus 71.6%, OR 0.71; 95% CI 0.49-1.05, P = 0.08) patient survival between 2 groups. Furthermore, recipients from obese and nonobese donors had a comparable risk of graft failure requiring retransplantation (OR 0.92; 95% CI 0.33-2.60, P = 0.88) or acute graft rejection (OR 0.70; 95% CI 0.45-1.11, P = 0.13). Conclusions A meta-analysis of the best available evidence (level 2a) demonstrates that donor obesity does not seem to have a negative impact on graft or patient outcomes. The available studies might be subject to selection bias as the grafts from obese donors are usually subject to biopsy to exclude steatosis and the recipients usually belong to the low-risk group. Future research is needed to evaluate the impact of donors subgrouped by various higher BMI on graft and patient-related outcomes as well as to capture data of the discarded grafts from obese donors; hence, selection criteria for the grafts that could be used for transplantation from obese donors is identified.
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Affiliation(s)
- Amr M.T. Alnagar
- Hepatobiliary and Pancreatic Surgery and Liver Transplant Unit, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom
| | - Shahab Hajibandeh
- Department of Hepatobiliary and Pancreatic Surgery, University Hospital of Wales, Cardiff, United Kingdom
| | - Shahin Hajibandeh
- Department of Hepatobiliary and Pancreatic Surgery, University Hospital Coventry, Coventry, United Kingdom
| | - Abdul R. Hakeem
- Department of Hepatobiliary and Liver Transplant Surgery, St James’s University Hospital NHS Trust, Leeds, United Kingdom
| | - Bobby V.M. Dasari
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
- Department of Liver Transplantation, HPB Surgery, Queen Elizabeth Hospital, Birmingham, United Kingdom
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3
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Berg T, Aehling NF, Bruns T, Welker MW, Weismüller T, Trebicka J, Tacke F, Strnad P, Sterneck M, Settmacher U, Seehofer D, Schott E, Schnitzbauer AA, Schmidt HH, Schlitt HJ, Pratschke J, Pascher A, Neumann U, Manekeller S, Lammert F, Klein I, Kirchner G, Guba M, Glanemann M, Engelmann C, Canbay AE, Braun F, Berg CP, Bechstein WO, Becker T, Trautwein C. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1397-1573. [PMID: 39250961 DOI: 10.1055/a-2255-7246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/11/2024]
Affiliation(s)
- Thomas Berg
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Niklas F Aehling
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Tony Bruns
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martin-Walter Welker
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin. Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Tobias Weismüller
- Klinik für Innere Medizin - Gastroenterologie und Hepatologie, Vivantes Humboldt-Klinikum, Berlin, Deutschland
| | - Jonel Trebicka
- Medizinische Klinik B für Gastroenterologie und Hepatologie, Universitätsklinikum Münster, Münster, Deutschland
| | - Frank Tacke
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Pavel Strnad
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martina Sterneck
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - Utz Settmacher
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Jena, Deutschland
| | - Daniel Seehofer
- Klinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Eckart Schott
- Klinik für Innere Medizin II - Gastroenterologie, Hepatologie und Diabetolgie, Helios Klinikum Emil von Behring, Berlin, Deutschland
| | | | - Hartmut H Schmidt
- Klinik für Gastroenterologie und Hepatologie, Universitätsklinikum Essen, Essen, Deutschland
| | - Hans J Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg, Regensburg, Deutschland
| | - Johann Pratschke
- Chirurgische Klinik, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Andreas Pascher
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Münster, Münster, Deutschland
| | - Ulf Neumann
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen, Essen, Deutschland
| | - Steffen Manekeller
- Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Bonn, Deutschland
| | - Frank Lammert
- Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - Ingo Klein
- Chirurgische Klinik I, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Gabriele Kirchner
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg und Innere Medizin I, Caritaskrankenhaus St. Josef Regensburg, Regensburg, Deutschland
| | - Markus Guba
- Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie, Universitätsklinikum München, München, Deutschland
| | - Matthias Glanemann
- Klinik für Allgemeine, Viszeral-, Gefäß- und Kinderchirurgie, Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - Cornelius Engelmann
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Ali E Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - Felix Braun
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
| | - Christoph P Berg
- Innere Medizin I Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - Wolf O Bechstein
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Thomas Becker
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
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Yoshiya S, Itoh S, Toshima T, Izumi T, Iseda N, Tsutsui Y, Toshida K, Nakayama Y, Ishikawa T, Tanaka Y, Ninomiya M, Yoshizumi T. Is preoperative weight reduction of living-donor liver transplant recipients and donors harmful to postoperative outcomes? J Gastrointest Surg 2024; 28:1033-1038. [PMID: 38631611 DOI: 10.1016/j.gassur.2024.04.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Revised: 04/05/2024] [Accepted: 04/12/2024] [Indexed: 04/19/2024]
Abstract
PURPOSE Although the incidence of recipients and donors with overweight and obesity is increasing worldwide, few reports have focused on outcomes of preoperative weight reduction (WR) in living-donor liver transplantation (LDLT). Therefore, we examined the outcomes and the impact of WR on the postoperative course. METHODS We analyzed 217 consecutive LDLT procedures performed from 2017 to 2022. We divided the recipients and donors into a WR group and non-WR group. RESULTS Twenty-two recipients (10.1%) achieved WR (preoperative recipient WR [RWR] group), reducing their weight by 6.8% ± 6.0% within 2.2 ± 1.4 months with a significant decrease in body mass index (BMI) (P < .0001). The RWR group showed no significant differences in short-term postoperative outcomes (operative factors, postoperative liver function tests, amount of ascites, and morbidity) or in the graft survival rate as a long-term outcome (P = .24) compared with the non-RWR group. Forty-one donors (18.9%) achieved WR (preoperative donor WR [DWR] group), reducing their weight by 9.7% ± 6.3% within 3.2 ± 5.8 months with a significant decrease in BMI (P < .0001). Compared with the non-DWR group, the DWR group showed no significant differences in short-term postoperative outcomes between themselves and recipients or in the graft survival rate (P = .49). Furthermore, WR resulted in an increase to 32 donor-eligible and 6 recipient-eligible patients. CONCLUSION WR in LDLT recipients and donors had no harmful effect on postoperative outcomes and should lead to increase recipients' chance of undergoing LDLT and to expand the donor pool.
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Affiliation(s)
- Shohei Yoshiya
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
| | - Shinji Itoh
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takeo Toshima
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takuma Izumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Norifumi Iseda
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yuriko Tsutsui
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Katsuya Toshida
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yuki Nakayama
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takuma Ishikawa
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yasushi Tanaka
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Mizuki Ninomiya
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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5
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Wozniak H, Naimimohasses S, Goto T, Sapisochin G, Sayed B, Ghanekar A, Cattral M, Selzner N. Long-Term Outcomes of Recipients of Liver Transplants from Living Donors Treated with a Very Low-Calorie Diet. J Transplant 2024; 2024:9024204. [PMID: 38725471 PMCID: PMC11081753 DOI: 10.1155/2024/9024204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Revised: 03/22/2024] [Accepted: 04/03/2024] [Indexed: 05/12/2024] Open
Abstract
The increasing prevalence of steatotic liver disease (SLD) in potential living donors is concerning, as it limits donor's availability amid rising demand. OPTIFAST very low-calorie diet (VLCD), a meal replacement product, effectively reduces weight and hepatic steatosis before transplantation. However, data on the outcomes of recipients of VLCD-treated donors are lacking. We conducted a single-center, retrospective study on 199 living donor liver transplant recipients at Toronto General Hospital, Canada, between January 2015 and January 2020. We compared the 1-year posttransplant outcomes between recipients who received organs from donors treated with VLCD (N = 34) for either weight loss or steatosis reduction, with those who did not require treatment (N = 165). Our analysis revealed no statistically significant differences in the rates of postoperative complications (23% vs 32.4%, p=0.3) or intensive care unit stays (70.9% vs 70.6%, p=1) between recipients of non-VLCD and VLCD grafts. Following adjusted multivariate logistic regression, receipt of VLCD grafts was not associated with increased hospital length of stay. In addition, one-year mortality did not differ between the two groups (4.2% non-VLCD recipients vs 2.9% VLCD recipients, p=0.6). OPTIFAST VLCD treatment for liver donors demonstrates positive and safe outcomes in recipients, expanding the pool of potential living donors for increased organ availability.
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Affiliation(s)
- Hannah Wozniak
- Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada
- Multi-Organ Transplant Program, Toronto General Hospital, University Health Network, Toronto, ON, Canada
| | - Sara Naimimohasses
- Multi-Organ Transplant Program, Toronto General Hospital, University Health Network, Toronto, ON, Canada
| | - Toru Goto
- Multi-Organ Transplant Program, Toronto General Hospital, University Health Network, Toronto, ON, Canada
| | - Gonzalo Sapisochin
- Multi-Organ Transplant Program, Toronto General Hospital, University Health Network, Toronto, ON, Canada
| | - Blayne Sayed
- Multi-Organ Transplant Program, Toronto General Hospital, University Health Network, Toronto, ON, Canada
| | - Anand Ghanekar
- Multi-Organ Transplant Program, Toronto General Hospital, University Health Network, Toronto, ON, Canada
| | - Mark Cattral
- Multi-Organ Transplant Program, Toronto General Hospital, University Health Network, Toronto, ON, Canada
| | - Nazia Selzner
- Multi-Organ Transplant Program, Toronto General Hospital, University Health Network, Toronto, ON, Canada
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6
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Oruc M, Gedik ME, Uner M, Ulug E, Unal RN, Gunaydin G, Dogrul AB. Effectiveness of metformin for the reversal of cold-ischemia-induced damage in hepatosteatosis. Clin Res Hepatol Gastroenterol 2024; 48:102314. [PMID: 38467276 DOI: 10.1016/j.clinre.2024.102314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2023] [Revised: 02/12/2024] [Accepted: 03/06/2024] [Indexed: 03/13/2024]
Abstract
BACKGROUND Primary dysfunction and rejection are more common in donor liver tissues with steatosis. AMP-activated protein kinase (AMPK) assumes organ-protective functions during ischemia. Metformin was used for the activation of AMPK in hepatocytes. The aim of this study is to investigate the effectiveness of metformin administration for the reversal of cold-ischemia-induced damage in hepatosteatosis. MATERIAL AND METHODS Seven-week-old C7BL56 male-mice (n = 109) were separated into four groups depending on diet type and metformin use. A specific diet model was followed for 10 weeks to induce hepatosteatosis. A group of the animals was administered with metformin for the last four weeks via oral gavage. After resection, the liver tissues were perfused and kept for 0-6-12-24 h in the UW solution. Histopathological examinations were performed, and Western blot was utilized to analyze p-AMPK and AMPK expression levels. RESULTS Hepatosteatosis decreased significantly with metformin. The steatotic liver group had more prominent pericentral inflammation, necrosis as well as showing a decreased and more delayed AMPK response than the non-fat group. All these alterations could be corrected using metformin. CONCLUSION Metformin can increase the resistance of livers with hepatosteatosis to cold-ischemia-induced damage, which in turn may pave the way for successful transplantation of fatty living-donor livers.
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Affiliation(s)
- Mustafa Oruc
- Department of General Surgery, Faculty Of Medicine, School of Medicine, Hacettepe University, Floor B, 06230, Ankara, Altindag 06230, Turkey
| | - Mustafa Emre Gedik
- Department of Basic Oncology, Hacettepe University Cancer Institute, Ankara 06230, Turkey
| | - Meral Uner
- Department of Pathology, Hacettepe University School of Medicine, Ankara 06230, Turkey
| | - Elif Ulug
- Department of Nutrition and Dietetics, Hacettepe University, Ankara 06230, Turkey
| | - Reyhan Nergiz Unal
- Department of Nutrition and Dietetics, Hacettepe University, Ankara 06230, Turkey
| | - Gurcan Gunaydin
- Department of Basic Oncology, Hacettepe University Cancer Institute, Ankara 06230, Turkey
| | - Ahmet Bulent Dogrul
- Department of General Surgery, Faculty Of Medicine, School of Medicine, Hacettepe University, Floor B, 06230, Ankara, Altindag 06230, Turkey.
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7
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Hakeem AR, Mathew JS, Aunés CV, Mazzola A, Alconchel F, Yoon YI, Testa G, Selzner N, Sarin SK, Lee KW, Soin A, Pomposelli J, Menon K, Goyal N, Kota V, Abu-Gazala S, Rodriguez-Davalos M, Rajalingam R, Kapoor D, Durand F, Kamath P, Jothimani D, Sudhindran S, Vij V, Yoshizumi T, Egawa H, Lerut J, Broering D, Berenguer M, Cattral M, Clavien PA, Chen CL, Shah S, Zhu ZJ, Ascher N, Bhangui P, Rammohan A, Emond J, Rela M. Preventing Small-for-size Syndrome in Living Donor Liver Transplantation: Guidelines From the ILTS-iLDLT-LTSI Consensus Conference. Transplantation 2023; 107:2203-2215. [PMID: 37635285 DOI: 10.1097/tp.0000000000004769] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/29/2023]
Abstract
Small-for-size syndrome (SFSS) is a well-recognized complication following liver transplantation (LT), with up to 20% developing this following living donor LT (LDLT). Preventing SFSS involves consideration of factors before the surgical procedure, including donor and recipient selection, and factors during the surgical procedure, including adequate outflow reconstruction, graft portal inflow modulation, and management of portosystemic shunts. International Liver Transplantation Society, International Living Donor Liver Transplantation Group, and Liver Transplant Society of India Consensus Conference was convened in January 2023 to develop recommendations for the prediction and management of SFSS in LDLT. The format of the conference was based on the Grading of Recommendations, Assessment, Development, and Evaluation system. International experts in this field were allocated to 4 working groups (diagnosis, prevention, anesthesia, and critical care considerations, and management of established SFSS). The working groups prepared evidence-based recommendations to answer-specific questions considering the currently available literature. The working group members, independent panel, and conference attendees served as jury to edit and confirm the final recommendations presented at the end of the conference by each working group separately. This report presents the final statements and evidence-based recommendations provided by working group 2 that can be implemented to prevent SFSS in LDLT patients.
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Affiliation(s)
- Abdul Rahman Hakeem
- Department of Hepatobiliary and Liver Transplant Surgery, St. James's University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
| | - Johns Shaji Mathew
- Department of GI, HPB & Multi-Organ Transplant, Rajagiri Hospitals, Kochi, India
| | - Carmen Vinaixa Aunés
- Hepatología y Trasplante Hepático, Servicio de Medicina Digestiva, Hospital Universitario y Politécnico La Fe, Valencia, Spain
- CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
| | - Alessandra Mazzola
- Sorbonne Université, Unité Médicale de Transplantation Hépatique, Hépato-gastroentérologie, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France
| | - Felipe Alconchel
- Department of Surgery and Transplantation, Virgen de la Arrixaca University Hospital, Murcia, Spain
- Biomedical Research Institute of Murcia, IMIB-Pascual Parrilla, Murcia, Spain
| | - Young-In Yoon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, Seoul, South Korea
| | - Giuliano Testa
- Department of Abdominal Transplantation, Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX
| | - Nazia Selzner
- Multi-Organ Transplant Program, Ajmera Transplant Center, University of Toronto, Toronto, ON, Canada
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University Hospital and Seoul National University College of Medicine, Seoul, South Korea
| | - Arvinder Soin
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta-The Medicity, Delhi, NCR, India
| | - James Pomposelli
- University of Colorado School of Medicine, Division of Transplant Surgery, Department of Surgery, Aurora, CO
| | - Krishna Menon
- Institute of Liver Diseases, King's College Hospital, London, United Kingdom
| | - Neerav Goyal
- Liver Transplant and Hepato-Pancreatobiliary Surgery Unit (LTHPS), Indraprastha Apollo Hospital, New Delhi, India
| | - Venugopal Kota
- Department of HPB Surgery and Liver Transplantation, Yashoda Hospitals, Secunderabad, Hyderabad, Telangana, India
| | - Samir Abu-Gazala
- Division of Transplant Surgery, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Manuel Rodriguez-Davalos
- Liver Center, Primary Children's Hospital; Transplant Services, Intermountain Transplant Center, Primary Children's Hospital, Salt Lake City, UT
| | - Rajesh Rajalingam
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
| | - Dharmesh Kapoor
- Department of Hepatology and Liver Transplantation, Yashoda Hospitals, Secunderabad, Hyderabad, Telangana, India
| | - Francois Durand
- Hepatology and Liver Intensive Care, Hospital Beaujon, Clichy University Paris Cité, Paris, France
| | - Patrick Kamath
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Dinesh Jothimani
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
| | - Surendran Sudhindran
- Department of Gastrointestinal Surgery and Solid Organ Transplantation, Amrita Institute of Medical Sciences, Kochi, India
| | - Vivek Vij
- Department of HPB Surgery and Liver Transplantation, Fortis Group of Hospitals, New Delhi, India
| | | | - Hiroto Egawa
- Department of Surgery, Tokyo Women's Medical University, Tokyo, Japan
| | - Jan Lerut
- Institute for Experimental and Clinical Research (IREC), Université catholique Louvain (UCL), Brussels, Belgium
| | - Dieter Broering
- Organ Transplant Center of Excellence, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Marina Berenguer
- Liver Unit, Ciberehd, Instituto de Investigación Sanitaria La Fe, Hospital Universitario y Politécnico La Fe, Universidad Valencia, Valencia, Spain
| | - Mark Cattral
- Multi-Organ Transplant Program, Ajmera Transplant Center, University of Toronto, Toronto, ON, Canada
| | - Pierre-Alain Clavien
- Department of Surgery and Transplantation, Swiss HPB Center, University Hospital Zurich, Zürich, Switzerland
| | - Chao-Long Chen
- Liver Transplantation Centre, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Samir Shah
- Department of Hepatology, Institute of Liver Disease, HPB Surgery and Transplant, Global Hospitals, Mumbai, India
| | - Zhi-Jun Zhu
- Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing, China
| | - Nancy Ascher
- Department of Surgery, University of California, San Francisco, San Francisco, CA
| | - Prashant Bhangui
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta-The Medicity, Delhi, NCR, India
| | - Ashwin Rammohan
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
| | - Jean Emond
- Liver and Abdominal Transplant Surgery, Columbia University Irving Medical Center, New York, NY
| | - Mohamed Rela
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
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Lalisang ANL, Putra AB, Zacharia NJ, Marbun VMG, Sihardo L, Syaiful RA, Ibrahim F, Jeo WS, Mazni Y, Putranto AS, Lalisang TJM. Characteristics of living liver donors in a national referral hospital in Indonesia: a 13-year experience with living donor liver transplantation. KOREAN JOURNAL OF TRANSPLANTATION 2023; 37:179-188. [PMID: 37671419 PMCID: PMC10583976 DOI: 10.4285/kjt.23.0030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Revised: 07/29/2023] [Accepted: 07/31/2023] [Indexed: 09/07/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma and biliary atresia lead to end-stage liver disease, which requires liver transplantation and is linked to increased mortality. Dr. Cipto Mangunkusumo Hospital is the national referral center in Indonesia and is the only center that routinely performs living donor liver transplantation (LDLT). This study presents the characteristics of living liver donors (LLDs) in Indonesia. METHODS Using the LDLT registry, we conducted a retrospective analysis of all approved donors from 2010 to 2022. The variables included clinical characteristics of the donors, graft types, and intraoperative and postoperative characteristics. RESULTS The LDLT rate has increased from 5.8 to 8.8 procedures/year in the last 8 years. The average age of the 76 LLDs was 31.8 years. They were predominantly female (59%) and lived within a family relationship (90%). Pediatric LDLT was more frequent than adult LDLT (88% vs. 12%, respectively). Most grafts (86%) were obtained by left lateral sectionectomy, with a median ratio of remnant liver volume to total liver volume of 79.5% (range, 47.7%-85.8%) and a mean graft-to-recipient weight ratio of 2.65%±1.21%. The median intensive care unit length of stay (LOS) was 2 days (range, 1-5 days) and the total hospital LOS was 7 days (range, 4-28 days). The complication rate was 23%. No donor mortality was reported. CONCLUSIONS LDLT in Indonesia has increased over the years. The shortage of donors for adult-to-adult liver transplantation is due to cultural differences and challenges in finding eligible donors. This study aims to explain the eligibility criteria of LLDs and contribute to creating a national policy.
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Affiliation(s)
- Arnetta Naomi Louise Lalisang
- Division of Digestive Surgery, Department of Surgery, Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia
- Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | | | | | - Vania Myralda Giamour Marbun
- Division of Digestive Surgery, Department of Surgery, Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia
- Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | - Lam Sihardo
- Division of Digestive Surgery, Department of Surgery, Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia
- Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | - Ridho Ardhi Syaiful
- Division of Digestive Surgery, Department of Surgery, Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia
- Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | - Febiansyah Ibrahim
- Division of Digestive Surgery, Department of Surgery, Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia
- Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | - Wifanto Saditya Jeo
- Division of Digestive Surgery, Department of Surgery, Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia
- Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | - Yarman Mazni
- Division of Digestive Surgery, Department of Surgery, Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia
- Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | - Agi Satria Putranto
- Division of Digestive Surgery, Department of Surgery, Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia
- Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | - Toar Jean Maurice Lalisang
- Division of Digestive Surgery, Department of Surgery, Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia
- Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
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9
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Sun C, Guo Y, Cong P, Tian Y, Gao X. Liver Lipidomics Analysis Revealed the Novel Ameliorative Mechanisms of L-Carnitine on High-Fat Diet-Induced NAFLD Mice. Nutrients 2023; 15:nu15061359. [PMID: 36986087 PMCID: PMC10053018 DOI: 10.3390/nu15061359] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 02/26/2023] [Accepted: 03/08/2023] [Indexed: 03/18/2023] Open
Abstract
The beneficial effects of L-carnitine on non-alcoholic fatty liver disease (NAFLD) were revealed in previous reports. However, the underlying mechanisms remain unclear. In this study, we established a high fat diet (HFD)-induced NAFLD mice model and systematically explored the effects and mechanisms of dietary L-carnitine supplementation (0.2% to 4%) on NAFLD. A lipidomics approach was conducted to identify specific lipid species involved in the ameliorative roles of L-carnitine in NAFLD. Compared with a normal control group, the body weight, liver weight, concentrations of TG in the liver and serum AST and ALT levels were dramatically increased by HFD feeding (p < 0.05), accompanied with obvious liver damage and the activation of the hepatic TLR4/NF-κB/NLRP3 inflammatory pathway. L-carnitine treatment significantly improved these phenomena and exhibited a clear dose–response relationship. The results of a liver lipidomics analysis showed that a total of 12 classes and 145 lipid species were identified in the livers. Serious disorders in lipid profiles were noticed in the livers of the HFD-fed mice, such as an increased relative abundance of TG and a decreased relative abundance of PC, PE, PI, LPC, LPE, Cer and SM (p < 0.05). The relative contents of PC and PI were significantly increased and that of DG were decreased after the 4% L-carnitine intervention (p < 0.05). Moreover, we identified 47 important differential lipid species that notably separated the experimental groups based on VIP ≥ 1 and p < 0.05. The results of a pathway analysis showed that L-carnitine inhibited the glycerolipid metabolism pathway and activated the pathways of alpha-linolenic acid metabolism, glycerophospholipid metabolism, sphingolipid metabolism and Glycosylphosphatidylinositol (GPI)-anchor biosynthesis. This study provides novel insights into the mechanisms of L-carnitine in attenuating NAFLD.
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Affiliation(s)
- Chengyuan Sun
- College of Life Sciences, Qingdao University, Qingdao 266071, China
| | - Yan Guo
- Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021, China
| | - Peixu Cong
- College of Food Science and Engineering, Ocean University of China, Qingdao 266100, China
| | - Yuan Tian
- Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021, China
- Correspondence: (Y.T.); (X.G.); Tel.: +86-138-8620-6248 (Y.T.); +86-133-6120-6713 (X.G.)
| | - Xiang Gao
- College of Life Sciences, Qingdao University, Qingdao 266071, China
- Correspondence: (Y.T.); (X.G.); Tel.: +86-138-8620-6248 (Y.T.); +86-133-6120-6713 (X.G.)
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10
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Kus AA, Yildiz I. Is it Possible to Avoid Liver Biopsy in Living Donors for Liver Transplantation by Using Two-Dimensional Shear Wave Elastography? Transplant Proc 2023; 55:363-368. [PMID: 36878747 DOI: 10.1016/j.transproceed.2023.01.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Accepted: 01/05/2023] [Indexed: 03/07/2023]
Abstract
PURPOSE The present study aims to evaluate the correlation of two-dimensional shear wave elastography results with histopathological findings performed simultaneously with liver biopsy (LB) in healthy liver transplant donors. METHODS A total of 53 living donors, 35 male and 18 female, were included in this prospective, observational, single-center study. Patients with abnormal liver function tests were not included in our study. Hepatosteatosis, fibrosis, and inflammation were evaluated with the Fatty Liver Inhibition of Progression and Steatosis, Activity, and Fibrosis algorithm of donor LB. RESULTS The mean age of the donors was 33.04 ± 9.07 years and the mean body mass index was 23.41 ± 6.23 kg/m2. The mean elastography kilo pascal (kPA) value of all donors was determined as 6.03 ± 2.32 kPa. The mean LB activity scores of the donors were found to be 1.64 ± 1.18 and ranged from 0 to 5. There was no significant correlation between elastography kPa value and pathologic activity score, steatosis score, balloon degeneration, and inflammation grade fibrosis scores (P > .05). CONCLUSION Shear wave elastography measurements showed that the predictive power of pathologic findings in donor LB was not sufficient.
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Affiliation(s)
- Aylin Altan Kus
- Acibadem University, Atakent Hospital, Department of Radiology, Istanbul, Turkey.
| | - Isil Yildiz
- Acibadem University, Atakent Hospital, Department of Radiology, Istanbul, Turkey
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11
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Minina MG, Voronov DV, Nevredimov AA, Tenchurina EA. Predictors of hepatic steatosis in living liver donors. RUSSIAN JOURNAL OF TRANSPLANTOLOGY AND ARTIFICIAL ORGANS 2022; 24:118-123. [DOI: 10.15825/1995-1191-2022-4-118-123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Fatty liver disease (steatosis) is considered a risk factor in donor liver transplantation (LT). Macrosteatosis (>50%) is associated with primary graft dysfunction and may reduce long-term recipient survival.Objective: to identify predictors of macrovesicular steatosis (>50%) by analyzing donor characteristics.Materials and methods. The retrospective study included 525 potential liver donors between January 1, 2019 and December 31, 2020. Clinical and morphological characteristics of donors were studied using logistic regression and receiver operating characteristic (ROC) analysis. Threshold values of parameters demonstrating statistical significance in multivariate analysis as predictors of >50% hepatic steatosis were obtained by ROC analysis based on calculation of the optimal cutoff point.Results. Diabetes mellitus (DM), cause of donor’s death (traumatic brain injury), alanine transaminase (ALT) >90 units/L and aspartate transaminase (AST) >110 units/L were predictors of >50% steatosis, revealed by time-zero biopsy in the donor. Almost identical sensitivity and specificity indicators were determined in ROC analysis for liver enzymes – ALT and AST – which were 69.1 and 80.6; 72.2 and 81.1, respectively. Given the obtained values, we can say that with elevated levels of liver enzymes in the donor’s blood, there is a high degree of probability of liver parenchymal damage, but low sensitivity indicates possible multifactoriality of liver damage, and fatty liver disease may be one of the factors, but there may also be no damage to the liver parenchyma. At the same time, the rather high specificity revealed in ROC analysis for liver enzymes is a reliable sign of the absence of fatty liver disease at enzyme values less than the threshold.Conclusion. The thresholds established for ALT and AST and their corresponding levels of sensitivity and specificity indicate that these parameters have a relatively low predictive level in the context of the presence of severe fatty liver disease in a donor. This allows, nevertheless, to use models built on their basis as screening models in the primary evaluation of liver donors.
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Affiliation(s)
- M. G. Minina
- Botkin City Clinical Hospital; Shumakov National Medical Research Center of Transplantology and Artificial Organs
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12
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Roeb E, Canbay A, Bantel H, Bojunga J, de Laffolie J, Demir M, Denzer UW, Geier A, Hofmann WP, Hudert C, Karlas T, Krawczyk M, Longerich T, Luedde T, Roden M, Schattenberg J, Sterneck M, Tannapfel A, Lorenz P, Tacke F. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:1346-1421. [PMID: 36100202 DOI: 10.1055/a-1880-2283] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- E Roeb
- Gastroenterologie, Medizinische Klinik II, Universitätsklinikum Gießen und Marburg, Gießen, Deutschland
| | - A Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - H Bantel
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - J Bojunga
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin., Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - J de Laffolie
- Allgemeinpädiatrie und Neonatologie, Zentrum für Kinderheilkunde und Jugendmedizin, Universitätsklinikum Gießen und Marburg, Gießen, Deutschland
| | - M Demir
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum und Campus Charité Mitte, Berlin, Deutschland
| | - U W Denzer
- Klinik für Gastroenterologie und Endokrinologie, Universitätsklinikum Gießen und Marburg, Marburg, Deutschland
| | - A Geier
- Medizinische Klinik und Poliklinik II, Schwerpunkt Hepatologie, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - W P Hofmann
- Gastroenterologie am Bayerischen Platz - Medizinisches Versorgungszentrum, Berlin, Deutschland
| | - C Hudert
- Klinik für Pädiatrie m. S. Gastroenterologie, Nephrologie und Stoffwechselmedizin, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - T Karlas
- Klinik und Poliklinik für Onkologie, Gastroenterologie, Hepatologie, Pneumologie und Infektiologie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - M Krawczyk
- Klinik für Innere Medizin II, Gastroent., Hepat., Endokrin., Diabet., Ern.med., Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - T Longerich
- Pathologisches Institut, Universitätsklinikum Heidelberg, Heidelberg, Deutschland
| | - T Luedde
- Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
| | - M Roden
- Klinik für Endokrinologie und Diabetologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
| | - J Schattenberg
- I. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz, Mainz, Deutschland
| | - M Sterneck
- Klinik für Hepatobiliäre Chirurgie und Transplantationschirurgie, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - A Tannapfel
- Institut für Pathologie, Ruhr-Universität Bochum, Bochum, Deutschland
| | - P Lorenz
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Berlin, Deutschland
| | - F Tacke
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum und Campus Charité Mitte, Berlin, Deutschland
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13
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Updated S2k Clinical Practice Guideline on Non-alcoholic Fatty Liver Disease (NAFLD) issued by the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS) - April 2022 - AWMF Registration No.: 021-025. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:e733-e801. [PMID: 36100201 DOI: 10.1055/a-1880-2388] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
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Dai S, Wang Z, Yang Y, Du P, Li X. PM 2.5 induced weight loss of mice through altering the intestinal microenvironment: Mucus barrier, gut microbiota, and metabolic profiling. JOURNAL OF HAZARDOUS MATERIALS 2022; 431:128653. [PMID: 35359108 DOI: 10.1016/j.jhazmat.2022.128653] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 03/03/2022] [Accepted: 03/07/2022] [Indexed: 06/14/2023]
Abstract
The experimental evidences linking PM2.5 exposure to weight status disorder and the associated mechanisms were lacked. Here, we demonstrated exposure of 198.52 μg/m3 PM2.5 (Baoji city, China) for 40 days induced body weight loss of male Balb/C mice, and then increased after 14-day recovery. Correspondingly, gut microbiota dysbiosis, ileum metabolism alterations, and histopathological changes of liver and ileum elucidated the underlying mechanism. The richness and function modules of flora in feces significantly reduced after exposure, and the ratios of Bacteroidetes/Firmicutes reduced from 1.58 to 0.79. At genus level, Lactobacillus and Clostridium increased markedly, while Bacteroides and Parabacteroides decreased at day 40. After recovery, Oscillospira became the dominant genus. Additionally, the key metabolites in the ileum mediated by PM2.5 identified by metabolomics included arachidonic acid, prostaglandin H2, prostaglandin F2α, 5(S)-HPETE, AMP, and deoxyadenosine. Accordingly, conjoint analysis between the gut micorbiota and metabolic profiling revealed suppression of Arachidonic acid metabolism, linoleic acid metabolism, and PPAR signaling pathway and stimulation of ABC transporters might contribute to the liver injury, ileum inflammation, and then weight loss of mice. Our findings suggested PM2.5 affected weight status of mice by meditating intestinal microenvironment, and provided new insight for further diagnosis of the air pollution dependent disease.
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Affiliation(s)
- Shuiping Dai
- National Center for Geriatrics Clinical Medicine Research, Department of Geriatrics and Gerontology, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Zhenglu Wang
- College of Oceanography, Hohai University, Nanjing, Jiangsu 210098, PR China.
| | - Ying Yang
- Center of Precision Medicine, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Peng Du
- Beijing Key Laboratory of Urban Hydrological Cycle and Sponge City Technology, College of Water Sciences, Beijing Normal University, Beijing 100875, PR China
| | - Xiqing Li
- Laboratory of Earth Surface Processes, College of Urban and Environmental Sciences, Peking University, Beijing 100871, PR China
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15
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Danis N, Weeks SR, Kim A, Baghdadi A, Ghadimi M, Kamel IR, Saberi B, Woreta T, Garonzik-Wang J, Philosophe B, Gurakar A, Loomba R. Noninvasive Risk Stratification for Nonalcoholic Fatty Liver Disease Among Living Liver Donor Candidates: A Proposed Algorithm. Liver Transpl 2022; 28:670-677. [PMID: 34753223 PMCID: PMC9683539 DOI: 10.1002/lt.26365] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 10/27/2021] [Accepted: 11/03/2021] [Indexed: 12/16/2022]
Abstract
To reduce waitlist mortality, living donor liver transplantation (LDLT) has increased over the past decade in the United States, but not at a rate sufficient to completely mitigate organ shortage. As a result, there are ongoing efforts to expand the living liver donor pool. Simultaneously, the prevalence of nonalcoholic fatty liver disease (NAFLD) in the general population has increased, which has significant implications on the pool of potential living liver donors. As such, a clinical assessment algorithm that exhaustively evaluates for NAFLD and fibrosis is critical to the safe expansion of LDLT. An ideal algorithm would employ safe and noninvasive methods, relying on liver biopsy only when necessary. While exclusion of NAFLD and fibrosis by noninvasive means is widely studied within the general population, there are no well-accepted guidelines for evaluation of living donors using these modalities. Here we review the current literature regarding noninvasive NALFD and fibrosis evaluation and propose a potential algorithm to apply these modalities for the selection of living liver donors.
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Affiliation(s)
- Nilay Danis
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Sharon R. Weeks
- Division of Transplant Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Ahyoung Kim
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Azarakhsh Baghdadi
- Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Maryam Ghadimi
- Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Ihab R. Kamel
- Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Behnam Saberi
- Division of Gastroenterology and Hepatology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA
| | - Tinsay Woreta
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD
| | | | - Benjamin Philosophe
- Division of Transplant Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Ahmet Gurakar
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Rohit Loomba
- NAFLD Research Center, Department of Medicine, University of California at San Diego, La Jolla, CA,Division of Gastroenterology, Department of Medicine, University of California at San Diego, La Jolla, CA,Division of Epidemiology, Department of Family and Preventive Medicine, University of California at San Diego, La Jolla, CA
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16
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Fang W, Gotoh K, Kobayashi S, Sasaki K, Iwagami Y, Yamada D, Tomimaru Y, Akita H, Noda T, Takahashi H, Doki Y, Eguchi H, Umeshita K. Short- and Long-Term Impacts of Overweight Status on Outcomes Among Living Liver Donors. Transplant Proc 2022; 54:690-695. [DOI: 10.1016/j.transproceed.2022.01.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 12/30/2021] [Accepted: 01/17/2022] [Indexed: 11/26/2022]
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Tien C, Remulla D, Kwon Y, Emamaullee J. Contemporary strategies to assess and manage liver donor steatosis: a review. Curr Opin Organ Transplant 2021; 26:474-481. [PMID: 34524179 PMCID: PMC8447219 DOI: 10.1097/mot.0000000000000893] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
PURPOSE OF REVIEW Due to a persistent shortage of donor livers, attention has turned toward ways of utilizing marginal grafts, particularly those with steatosis, without incurring inferior outcomes. Here we review the evaluation and utilization of steatotic liver allografts, highlight recently published data, and discuss novel methods of graft rehabilitation. RECENT FINDINGS Although severe liver allograft (>60%) steatosis has been associated with inferior graft and recipient outcomes, mild (<30%) steatosis has not. There is ongoing debate regarding safe utilization of grafts with moderate (30-60%) steatosis. Presently, no established protocols for evaluating steatosis in donor candidates or utilizing such grafts exist. Liver biopsy is accepted as the gold standard technique, though noninvasive methods have shown promise in accurately predicting steatosis. More recently, machine perfusion has been shown to enhance ex situ liver function and reduce steatosis, emerging as a potential means of optimizing steatotic grafts prior to transplantation. SUMMARY Steatotic liver allografts constitute a large proportion of deceased donor organs. Further work is necessary to define safe upper limits for the acceptable degree of steatosis, develop standardized evaluation protocols, and establish utilization guidelines that prioritize safety. Machine perfusion has shown promise in rehabilitating steatotic grafts and offers the possibility of expanding the deceased donor pool.
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Affiliation(s)
- Christine Tien
- Keck School of Medicine, University of Southern California, Los Angeles, CA
| | - Daphne Remulla
- Keck School of Medicine, University of Southern California, Los Angeles, CA
| | - Yong Kwon
- Keck School of Medicine, University of Southern California, Los Angeles, CA
- Department of Surgery, University of Southern California, Los Angeles, CA
| | - Juliet Emamaullee
- Keck School of Medicine, University of Southern California, Los Angeles, CA
- Department of Surgery, University of Southern California, Los Angeles, CA
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18
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Lin F, Zhen F, Yan X, Shaojun Y, Guizhu P, Yanfeng W, Qifa Y. Hypothermic oxygenated perfusion with defatting cocktail further improves steatotic liver grafts in a transplantation rat model. Artif Organs 2021; 45:E304-E316. [PMID: 33908066 DOI: 10.1111/aor.13976] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 03/06/2021] [Accepted: 03/19/2021] [Indexed: 12/18/2022]
Abstract
In this study, we evaluated the restoring and defatting effect of hypothermic oxygenated perfusion (HOPE) on severe steatotic liver grafts with a defatting cocktail (DF) in a rat model. Severe (≥60%) hepatic macrosteatosis was induced by a high-fat diet (HFD) for 6 weeks, after which the rats were randomly divided into four following groups: Control group, with lean livers being preserved in static cold storage (SCS) at 0°C-4°C for 45 minutes; SCS group, with a steatotic liver graft (SLG) being preserved in SCS at 0°C-4°C for 4 hours; HOPE group, where SLG was perfused with 3-hours HOPE followed by 1-hours SCS; and HOPE + DF group, HOPE with the addition of DF. Graft function after orthotopic liver transplantation was assessed in terms of mitochondrial function (adenosine triphosphate [ATP], Glycogen), endoplasmic reticulum stress (PPY, GRP78, CHOP, and ATF-6), cell apoptosis (Tunel assay, Caspase-3), inflammatory level (HMGB1, TLR4, IL-1β, IL-6. TNF-α, Factor V), and posttransplantation survival. HOPE protected steatotic liver grafts from microcirculation disturbance and endoplasmic reticulum stress and then promoted ATP and glycogen synthesis that improved mitochondrial function. Meanwhile, under conditions of ischemia-reperfusion injury, it prevented nuclear injury and endothelial damage by suppressing the release of an inflammatory mediator. The high efficacy of HOPE was enhanced after the addition of the DF. DF agents cannot promote the lipid decomposition of the steatotic liver graft at 0°C-4°C, but they can further improve steatotic liver and postoperative survival compared to the HOPE. The defatted steatotic liver grafts can be safely used in rat orthotopic liver transplantation.
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Affiliation(s)
- Fan Lin
- Hubei Key Laboratory of Medical Technology on Transplantation, Transplant Center of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Zhongnan Hospital of Wuhan University, Wuhan, PR China
| | - Fu Zhen
- Hubei Key Laboratory of Medical Technology on Transplantation, Transplant Center of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Zhongnan Hospital of Wuhan University, Wuhan, PR China
| | - Xiong Yan
- Hubei Key Laboratory of Medical Technology on Transplantation, Transplant Center of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Zhongnan Hospital of Wuhan University, Wuhan, PR China
| | - Ye Shaojun
- Hubei Key Laboratory of Medical Technology on Transplantation, Transplant Center of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Zhongnan Hospital of Wuhan University, Wuhan, PR China
| | - Peng Guizhu
- Hubei Key Laboratory of Medical Technology on Transplantation, Transplant Center of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Zhongnan Hospital of Wuhan University, Wuhan, PR China
| | - Wang Yanfeng
- Hubei Key Laboratory of Medical Technology on Transplantation, Transplant Center of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Zhongnan Hospital of Wuhan University, Wuhan, PR China
| | - Ye Qifa
- Hubei Key Laboratory of Medical Technology on Transplantation, Transplant Center of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Zhongnan Hospital of Wuhan University, Wuhan, PR China
- Research Center of National Health Ministry on Transplantation Medicine Engineering and Technology, The 3rd Xiangya Hospital of Central South University, Changsha, PR China
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Trakroo S, Bhardwaj N, Garg R, Modaresi Esfeh J. Weight loss interventions in living donor liver transplantation as a tool in expanding the donor pool: A systematic review and meta-analysis. World J Gastroenterol 2021; 27:3682-3692. [PMID: 34239278 PMCID: PMC8240053 DOI: 10.3748/wjg.v27.i24.3682] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Revised: 03/08/2021] [Accepted: 05/27/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND With increasing rates of liver transplantation and a stagnant donor pool, the annual wait list removals have remained high. Living donor liver transplantation (LDLT) is an established modality in expanding the donor pool and is the primary method of liver donation in large parts of the world. Marginal living donors, including those with hepatic steatosis, have been used to expand the donor pool. However, due to negative effects of steatosis on graft and recipient outcomes, current practice excludes overweight or obese donors with more than 10% macro vesicular steatosis. This has limited a potentially important source to help expand the donor pool. Weight loss is known to improve or resolve steatosis and rapid weight loss with short-term interventions have been used to convert marginal donors to low-risk donors in a small series of studies. There is, however, a lack of a consensus driven standardized approach to such interventions. AIM To assess the available data on using weight loss interventions in potential living liver donors with steatotic livers and investigated the feasibility, efficacy, and safety of using such donors on the donor, graft and recipient outcomes. The principal objective was to assess if using such treated donor livers, could help expand the donor pool. METHODS We performed a comprehensive literature review and meta-analysis on studies examining the role of short-term weight loss interventions in potential living liver donors with hepatic steatosis with the aim of increasing liver donation rates and improving donor, graft, and recipient outcomes. RESULTS A total of 6 studies with 102 potential donors were included. Most subjects were males (71). All studies showed a significant reduction in body mass index post-intervention with a mean difference of -2.08 (-3.06, 1.10, I 2 = 78%). A significant reduction or resolution of hepatic steatosis was seen in 93 of the 102 (91.2%). Comparison of pre- and post-intervention liver biopsies showed a significant reduction in steatosis with a mean difference of -21.22 (-27.02, -15.43, I 2 = 56%). The liver donation rates post-intervention was 88.5 (74.5, 95.3, I 2 = 42%). All donors who did not undergo LDLT had either recipient reasons or had fibrosis/steatohepatitis on post intervention biopsies. Post-operative biliary complications in the intervention group were not significantly different compared to controls with an odds ratio of 0.96 [(0.14, 6.69), I 2 = 0]. The overall post-operative donor, graft, and recipient outcomes in treated donors were not significantly different compared to donors with no steatosis. CONCLUSION Use of appropriate short term weight loss interventions in living liver donors is an effective tool in turning marginal donors to low-risk donors and therefore in expanding the donor pool. It is feasible and safe, with comparable donor, graft, and recipient outcomes, to non-obese donors. Larger future prospective studies are needed.
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Affiliation(s)
- Sushrut Trakroo
- Department of Hospital Medicine, Cleveland Clinic, Cleveland, OH 44195, United States
| | - Nakul Bhardwaj
- Department of Internal Medicine, Cleveland Clinic, Cleveland, OH 44195, United States
| | - Rajat Garg
- Department of Internal Medicine, Cleveland Clinic, Cleveland, OH 44195, United States
| | - Jamak Modaresi Esfeh
- Department of Gastroenterology and Transplant Hepatology, Cleveland Clinic, Cleveland, OH 44195, United States
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20
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Caballeria-Casals A, Micó-Carnero M, Rojano-Alfonso C, Maroto-Serrat C, Casillas-Ramírez A, Álvarez-Mercado AI, Gracia-Sancho J, Peralta C. Role of FGF15 in Hepatic Surgery in the Presence of Tumorigenesis: Dr. Jekyll or Mr. Hyde? Cells 2021; 10:1421. [PMID: 34200439 PMCID: PMC8228386 DOI: 10.3390/cells10061421] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 05/26/2021] [Accepted: 06/04/2021] [Indexed: 12/11/2022] Open
Abstract
The pro-tumorigenic activity of fibroblast growth factor (FGF) 19 (FGF15 in its rodent orthologue) in hepatocellular carcinoma (HCC), as well as the unsolved problem that ischemia-reperfusion (IR) injury supposes in liver surgeries, are well known. However, it has been shown that FGF15 administration protects against liver damage and regenerative failure in liver transplantation (LT) from brain-dead donors without tumor signals, providing a benefit in avoiding IR injury. The protection provided by FGF15/19 is due to its anti-apoptotic and pro-regenerative properties, which make this molecule a potentially beneficial or harmful factor, depending on the disease. In the present review, we describe the preclinical models currently available to understand the signaling pathways responsible for the apparent controversial effects of FGF15/19 in the liver (to repair a damaged liver or to promote tumorigenesis). As well, we study the potential pharmacological use that has the activation or inhibition of FGF15/19 pathways depending on the disease to be treated. We also discuss whether FGF15/19 non-pro-tumorigenic variants, which have been developed for the treatment of liver diseases, might be promising approaches in the surgery of hepatic resections and LT using healthy livers and livers from extended-criteria donors.
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Affiliation(s)
- Albert Caballeria-Casals
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain; (A.C.-C.); (M.M.-C.); (C.R.-A.)
| | - Marc Micó-Carnero
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain; (A.C.-C.); (M.M.-C.); (C.R.-A.)
| | - Carlos Rojano-Alfonso
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain; (A.C.-C.); (M.M.-C.); (C.R.-A.)
| | | | - Araní Casillas-Ramírez
- Hospital Regional de Alta Especialidad de Ciudad Victoria “Bicentenario 2010”, Ciudad Victoria 87087, Mexico;
- Facultad de Medicina e Ingeniería en Sistemas Computacionales de Matamoros, Universidad Autónoma de Tamaulipas, Matamoros 87300, Mexico
| | - Ana I. Álvarez-Mercado
- Departamento de Bioquímica y Biología Molecular II, Escuela de Farmacia, Universidad de Granada, 18071 Granada, Spain;
- Institute of Nutrition and Food Technology “José Mataix”, Center of Biomedical Research, University of Granada, 18016 Armilla, Spain
- Instituto de Investigación Biosanitaria ibs.GRANADA, Complejo Hospitalario Universitario de Granada, 18014 Granada, Spain
| | - Jordi Gracia-Sancho
- Liver Vascular Biology Research Group, Barcelona Hepatic Hemodynamic Laboratory IDIBAPS, 03036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 08036 Barcelona, Spain
| | - Carmen Peralta
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain; (A.C.-C.); (M.M.-C.); (C.R.-A.)
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21
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Richards JA, Randle LV, Butler MChir AJ, Martin JL, Fedotovs A, Davies SE, Watson CJE, Robertson PA. Pilot study of a noninvasive real-time optical backscatter probe in liver transplantation. Transpl Int 2021; 34:709-720. [PMID: 33462839 DOI: 10.1111/tri.13823] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Revised: 10/30/2020] [Accepted: 01/15/2021] [Indexed: 11/28/2022]
Abstract
Transplantation of severely steatotic donor livers is associated with early allograft dysfunction and poorer graft survival. Histology remains the gold standard diagnostic of donor steatosis despite the lack of consensus definition and its subjective nature. In this prospective observational study of liver transplant patients, we demonstrate the feasibility of using a handheld optical backscatter probe to assess the degree of hepatic steatosis and correlate the backscatter readings with clinical outcomes. The probe is placed on the surface of the liver and emits red and near infrared light from the tip of the device and measures the amount of backscatter of light from liver tissue via two photodiodes. Measurement of optical backscatter (Mantel-Cox P < 0.0001) and histopathological scoring of macrovesicular steatosis (Mantel-Cox P = 0.046) were predictive of 5-year graft survival. Recipients with early allograft dysfunction defined according to both Olthoff (P = 0.0067) and MEAF score (P = 0.0097) had significantly higher backscatter levels from the donor organ. Backscatter was predictive of graft loss (AUC 0.75, P = 0.0045). This study demonstrates the feasibility of real-time measurement of optical backscatter in donor livers. Early results indicate readings correlate with steatosis and may give insight to graft outcomes such as early allograft dysfunction and graft loss.
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Affiliation(s)
- James A Richards
- Department of Surgery, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.,NIHR Blood and Transplant Research Unit (BTRU) at the University of Cambridge in collaboration with Newcastle University and in partnership with NHS Blood and Transplant (NHSBT), Cambridge, UK.,The National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre, Cambridge, UK
| | - Lucy V Randle
- Department of Surgery, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.,NIHR Blood and Transplant Research Unit (BTRU) at the University of Cambridge in collaboration with Newcastle University and in partnership with NHS Blood and Transplant (NHSBT), Cambridge, UK.,The National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre, Cambridge, UK
| | - Andrew J Butler MChir
- Department of Surgery, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.,NIHR Blood and Transplant Research Unit (BTRU) at the University of Cambridge in collaboration with Newcastle University and in partnership with NHS Blood and Transplant (NHSBT), Cambridge, UK.,The National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre, Cambridge, UK
| | - Jack L Martin
- Department of Surgery, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.,NIHR Blood and Transplant Research Unit (BTRU) at the University of Cambridge in collaboration with Newcastle University and in partnership with NHS Blood and Transplant (NHSBT), Cambridge, UK.,The National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre, Cambridge, UK
| | - Arturs Fedotovs
- Department of Surgery, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.,NIHR Blood and Transplant Research Unit (BTRU) at the University of Cambridge in collaboration with Newcastle University and in partnership with NHS Blood and Transplant (NHSBT), Cambridge, UK.,The National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre, Cambridge, UK
| | - Susan E Davies
- Department of Pathology, Cambridge University Hospitals, Addenbrooke's Hospital, Cambridge, UK
| | - Christopher J E Watson
- Department of Surgery, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.,NIHR Blood and Transplant Research Unit (BTRU) at the University of Cambridge in collaboration with Newcastle University and in partnership with NHS Blood and Transplant (NHSBT), Cambridge, UK.,Department of Pathology, Cambridge University Hospitals, Addenbrooke's Hospital, Cambridge, UK
| | - Paul A Robertson
- Department of Engineering, Electrical Engineering Division, University of Cambridge, Cambridge, UK
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22
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Steatotic Livers Are More Susceptible to Ischemia Reperfusion Damage after Transplantation and Show Increased γδ T Cell Infiltration. Int J Mol Sci 2021; 22:ijms22042036. [PMID: 33670793 PMCID: PMC7922678 DOI: 10.3390/ijms22042036] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 02/04/2021] [Accepted: 02/06/2021] [Indexed: 12/27/2022] Open
Abstract
Liver transplantation (LTx) is often the only possible therapy for many end-stage liver diseases, but successful long-term transplant outcomes are limited by multiple factors, including ischemia reperfusion injury (IRI). This situation is aggravated by a shortage of transplantable organs, thus encouraging the use of inferior quality organs. Here, we have investigated early hepatic IRI in a retrospective, exploratory, monocentric case-control study considering organ marginality. We analyzed standard LTx biopsies from 46 patients taken at the end of cold organ preparation and two hours after reperfusion, and we showed that early IRI was present after two hours in 63% of cases. Looking at our data in general, in accordance with Eurotransplant criteria, a marginal transplant was allocated at our institution in about 54% of cases. We found that patients with a marginal-organ LTx showing evidence of IRI had a significantly worse one-year survival rate (51% vs. 75%). As we saw in our study cohort, the marginality of these livers was almost entirely due to steatosis. In contrast, survival rates in patients receiving a non-marginal transplant were not influenced by the presence or absence of IRI. Poorer outcomes in marginal organs prompted us to examine pre- and post-reperfusion biopsies, and it was revealed that transplants with IRI demonstrated significantly greater T cell infiltration. Molecular analyses showed that higher mRNA expression levels of CXCL-1, CD3 and TCRγ locus genes were found in IRI livers. We therefore conclude that the marginality of an organ, namely steatosis, exacerbates early IRI by enhancing effector immune cell infiltration. Preemptive strategies targeting immune pathways could increase the safety of using marginal organs for LTx.
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23
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Lombardi R, Pisano G, Fargion S, Fracanzani AL. Cardiovascular involvement after liver transplantation: role of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. EXPLORATION OF MEDICINE 2021. [DOI: 10.37349/emed.2021.00030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Patients submitted to liver transplantation (LT) are exposed to high risk of cardiovascular (CV) complications which are the main determinants of both short-term and long-term morbidity and mortality in LT. Non-alcoholic fatty liver disease (NAFLD) is a very frequent condition in general population and is associated with a high risk of cardiovascular disease (CVD) which represents the first cause of death of these patients. NAFLD is predicted to become the first indication to LT and nowadays is also frequently detected in patients submitted to LT for other indications. Thus, the risk of CVD in patients submitted to LT is forecasted to increase in the next years. In this review the extent of CV involvement in patients submitted to LT and the role of NAFLD, either recurring after transplantation or as de novo presentation, in increasing CV risk is analysed. The risk of developing metabolic alterations, including diabetes, hypertension, dyslipidemia and weight gain, all manifestations of metabolic syndrome, occurring in the first months after LT, is depicted. The different presentations of cardiac involvement, represented by early atherosclerosis, coronary artery disease, heart failure and arrhythmias in patients with NAFLD submitted to LT is described. In addition, the tools to detect cardiac alterations either before or after LT is reported providing the possibility for an early diagnosis of CVD and an early therapy able to reduce morbidity and mortality for these diseases. The need for long-term concerted multidisciplinary activity with dietary counseling and exercise combined with drug treatment of all manifestations of metabolic syndrome is emphasized.
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Affiliation(s)
- Rosa Lombardi
- General Medicine and Metabolic Diseases, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy 2Department of Pathophysiology and Transplantation, University of the Study of Milan, 20122 Milan, Italy
| | - Giuseppina Pisano
- General Medicine and Metabolic Diseases, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Silvia Fargion
- Department of Pathophysiology and Transplantation, University of the Study of Milan, 20122 Milan, Italy
| | - Anna Ludovica Fracanzani
- General Medicine and Metabolic Diseases, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy 2Department of Pathophysiology and Transplantation, University of the Study of Milan, 20122 Milan, Italy
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24
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Moghe A, Ganesh S, Humar A, Molinari M, Jonassaint N. Expanding Donor Selection and Recipient Indications for Living Donor Liver Transplantation. Clin Liver Dis 2021; 25:121-135. [PMID: 33978574 DOI: 10.1016/j.cld.2020.08.011] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
There is an acute shortage of deceased donor organs for liver transplantation in the United States. Nearly a third of patients either die or become too sick for transplant while on the transplant waitlist. Living donor liver transplantation (LDLT) bridges the gap between demand and supply of organs for liver transplantation. This article reviews current living donor selection criteria, and avenues for expansion of criteria with novel surgical techniques and ongoing outcomes research. Ways in which institutions can establish and expand LDLT programs using the Living Donor Champion model are discussed. Efforts to expand recipient indications for LDLT are described.
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Affiliation(s)
- Akshata Moghe
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh Medical Center, Mezzanine Level, C-Wing, PUH 200 Lothrop Street, Pittsburgh, PA 15213, USA. https://twitter.com/AkshataMoghe
| | - Swaytha Ganesh
- Living Donor Liver Transplantation Program, Department of Medicine, University of Pittsburgh Medical Center, Center for Liver Diseases, 3471 Fifth Avenue, 900 Kaufmann Building, Pittsburgh, PA 15213, USA
| | - Abhinav Humar
- Division of Abdominal Transplantation Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, UPMC Montefiore, Seventh Floor - N723, 3459 Fifth Avenue, Pittsburgh, PA 15213, USA
| | - Michele Molinari
- Department of Surgery, University of Pittsburgh Medical Center, UPMC Montefiore, N761, 3459 Fifth Avenue, Pittsburgh, PA 15213, USA
| | - Naudia Jonassaint
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Pittsburgh Medical Center, Center for Liver Diseases, 3471 Fifth Avenue, 900 Kaufmann Building, Pittsburgh, PA 15213, USA.
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25
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Beltzer C, Quante M, Rheinberger M, Baba HA, Saner F, Fend F, Biet T, Königsrainer A, Nadalin S. [Percutaneous liver biopsy before organ removal-Impact on organ allocation and costs in liver transplantation]. Chirurg 2021; 92:49-61. [PMID: 32430545 PMCID: PMC7820082 DOI: 10.1007/s00104-020-01192-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Hintergrund Der Stellenwert und die Sicherheit einer perkutanen Leberbiopsie (PLB) bei hirntoten Spendern vor Organentnahme sowie der Einfluss der PLB auf die Organallokation und die Kosten im Rahmen der Lebertransplantation (LT) in der Eurotransplant-Region (ET), werden weiterhin diskutiert. Material und Methoden Eine perkutane Leberbiopsie vor Organentnahme erfolgte bei 36 hirntoten Spendern. Die Komplikationsrate, Spendercharakteristika, Ultraschallbefunde, die makroskopische Einschätzung und die histologischen Ergebnisse der PLB wurden analysiert. Zusätzlich wurde eine landesweite Umfrage unter 11 Lebertransplantationsexperten durchgeführt. Der Bedarf einer PLB und ihre Auswirkungen auf den Prozess der Organallokation wurden evaluiert. Mögliche Kosteneinsparungen wurden für verschiedene Szenarien auf der Grundlage von Kostendaten der Deutschen Stiftung Organtransplantation berechnet. Ergebnisse Es wurden keine Komplikationen durch die PLB beobachtet. Die Umfrage ergab, dass das Ergebnis der PLB einen erheblichen Einfluss auf die Allokation von Spenderorganen hat, insbesondere bei solchen mit „extended donor criteria (EDC)“. Die Kostenberechnung ergab ein enormes Kosteneinsparungspotenzial durch eine optimierte Allokation und die Vermeidung unnötiger Organentnahmen. Schlussfolgerung Die PLB ist ein sicheres Verfahren und besitzt ein enormes Potenzial für die Optimierung der Organallokation vor Organentnahme durch eine Reduzierung der kalten Ischämiezeit, Vermeidung unnötiger Verwerfungen von Spenderorganen sowie Kosteneinsparungen. Die klinische Relevanz und der Einfluss der PLB auf die Organallokation konnte durch unsere Daten herausgestellt werden.
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Affiliation(s)
- Christian Beltzer
- Klinik für Allgemeine, Viszeral- und Transplantationschirurgie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - Markus Quante
- Klinik für Allgemeine, Viszeral- und Transplantationschirurgie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - Myriam Rheinberger
- Klinik für Allgemeine, Viszeral- und Transplantationschirurgie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | | | - Fuat Saner
- Klinik für Allgemein‑, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen, Essen, Deutschland
| | - Falko Fend
- Institut für Pathologie und Neuropathologie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - Thomas Biet
- Deutsche Stiftung Organtransplantation, Frankfurt am Main, Deutschland
| | - Alfred Königsrainer
- Klinik für Allgemeine, Viszeral- und Transplantationschirurgie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - Silvio Nadalin
- Klinik für Allgemeine, Viszeral- und Transplantationschirurgie, Universitätsklinikum Tübingen, Tübingen, Deutschland.
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26
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Inhibition of MLKL Attenuates Necroptotic Cell Death in a Murine Cell Model of Ischaemia Injury. J Clin Med 2021; 10:jcm10020212. [PMID: 33435617 PMCID: PMC7826539 DOI: 10.3390/jcm10020212] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 01/01/2021] [Accepted: 01/07/2021] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Steatosis in donor livers poses a major risk of organ dysfunction due to their susceptibility to ischaemia-reperfusion (I/R) injury during transplant. Necroptosis, a novel form of programmed cell death, is orchestrated by receptor-interacting protein kinase 1 (RIPK1), receptor-interacting protein kinase 3 (RIPK3) and mixed-lineage kinase domain-like pseudokinase (MLKL), has been implicated in I/R injury. Here we investigated the mechanisms of cell death pathways in an in vitro model of hepato-steatotic ischaemia. METHODS Free fatty acid (FFA) treated alpha mouse liver 12 (AML-12) cells were incubated in oxygen-glucose-deprivation (OGD) conditions as seen during ischaemia. RESULTS We found that OGD triggered upregulation of insoluble fraction of RIPK3 and MLKL in FFA + OGD cells compared to FFA control cells. We report that intervention with small interfering (si) MLKL and siRIPK3 significantly attenuated cell death in FFA + OGD cells. Absence of activated CASPASE8 and cleaved-CASPASE3, no change in the expression of CASPASE1 and prostaglandin-endoperoxide synthase 2 (Ptgs2) in FFA + OGD treated cells compared to FFA control cells indicated that apoptosis, pyroptosis and ferroptosis, respectively, are unlikely to be active in this model. CONCLUSION Our findings indicate that RIPK3-MLKL dependent necroptosis contributed to cell death in our in vitro model. Both MLKL and RIPK3 are promising therapeutic targets to inhibit necroptosis during ischaemic injury in fatty liver.
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27
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Liss KH, Ek SE, Lutkewitte AJ, Pietka TA, He M, Skaria P, Tycksen E, Ferguson D, Blanc V, Graham MJ, Hall AM, McGill MR, McCommis KS, Finck BN. Monoacylglycerol Acyltransferase 1 Knockdown Exacerbates Hepatic Ischemia/Reperfusion Injury in Mice With Hepatic Steatosis. Liver Transpl 2021; 27:116-133. [PMID: 32916011 PMCID: PMC7785593 DOI: 10.1002/lt.25886] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Revised: 08/19/2020] [Accepted: 08/27/2020] [Indexed: 12/13/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is becoming the most common indication for liver transplantation. The growing prevalence of NAFLD not only increases the demand for liver transplantation, but it also limits the supply of available organs because steatosis predisposes grafts to ischemia/reperfusion injury (IRI) and many steatotic grafts are discarded. We have shown that monoacylglycerol acyltransferase (MGAT) 1, an enzyme that converts monoacylglycerol to diacylglycerol, is highly induced in animal models and patients with NAFLD and is an important mediator in NAFLD-related insulin resistance. Herein, we sought to determine whether Mogat1 (the gene encoding MGAT1) knockdown in mice with hepatic steatosis would reduce liver injury and improve liver regeneration following experimental IRI. Antisense oligonucleotides (ASO) were used to knockdown the expression of Mogat1 in a mouse model of NAFLD. Mice then underwent surgery to induce IRI. We found that Mogat1 knockdown reduced hepatic triacylglycerol accumulation, but it unexpectedly exacerbated liver injury and mortality following experimental ischemia/reperfusion surgery in mice on a high-fat diet. The increased liver injury was associated with robust effects on the hepatic transcriptome following IRI including enhanced expression of proinflammatory cytokines and chemokines and suppression of enzymes involved in intermediary metabolism. These transcriptional changes were accompanied by increased signs of oxidative stress and an impaired regenerative response. We have shown that Mogat1 knockdown in a mouse model of NAFLD exacerbates IRI and inflammation and prolongs injury resolution, suggesting that Mogat1 may be necessary for liver regeneration following IRI and that targeting this metabolic enzyme will not be an effective treatment to reduce steatosis-associated graft dysfunction or failure.
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Affiliation(s)
- Kim H.H. Liss
- Department of Pediatrics, Washington University School of Medicine, St. Louis, MO
| | - Shelby E. Ek
- Department of Pediatrics, Washington University School of Medicine, St. Louis, MO
- Department of Medicine, Washington University School of Medicine, St. Louis, MO
| | | | - Terri A. Pietka
- Department of Medicine, Washington University School of Medicine, St. Louis, MO
| | - Mai He
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO
| | - Priya Skaria
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO
| | - Eric Tycksen
- Department of Genome Technology Access Center, McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO
| | - Daniel Ferguson
- Department of Medicine, Washington University School of Medicine, St. Louis, MO
| | - Valerie Blanc
- Department of Medicine, Washington University School of Medicine, St. Louis, MO
| | | | - Angela M. Hall
- Department of Medicine, Washington University School of Medicine, St. Louis, MO
| | - Mitchell R. McGill
- Department of Environmental and Occupational Health, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR
| | - Kyle S. McCommis
- Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO
| | - Brian N. Finck
- Department of Medicine, Washington University School of Medicine, St. Louis, MO
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28
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Fagenson AM, Pitt HA, Moten AS, Karhadkar SS, Di Carlo A, Lau KN. Fatty liver: The metabolic syndrome increases major hepatectomy mortality. Surgery 2020; 169:1054-1060. [PMID: 33358472 DOI: 10.1016/j.surg.2020.11.021] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Revised: 11/01/2020] [Accepted: 11/17/2020] [Indexed: 12/19/2022]
Abstract
BACKGROUND As the obesity epidemic worsens, the prevalence of fatty liver disease has increased. However, minimal data exist on the impact of combined fatty liver and metabolic syndrome on hepatectomy outcomes. Therefore, the aim of this analysis is to measure the outcomes of patients who do and do not have a fatty liver undergoing hepatectomy in the presence and absence of the metabolic syndrome. METHODS Patients with fatty and normal livers undergoing major hepatectomy (≥3 segments) were identified in the 2014 to 2018 American College of Surgeon National Surgical Quality Improvement Program database. Patients undergoing partial hepatectomy and those with missing liver texture data were excluded. Propensity matching was used and adjusted for multiple variables. A subgroup analysis stratified by the metabolic syndrome (body mass index ≥30 kg/m2, hypertension and diabetes) was performed. Demographics and outcomes were compared by χ2 and Mann-Whitney tests. RESULTS Of 2,927 hepatectomies, 30% of patients (N = 863) had a fatty liver. The median body mass index was 28.6, and the metabolic syndrome was present in 6.3% of patients (N = 184). After propensity matching, 863 patients with fatty and 863 with normal livers were compared. Multiple outcomes were significantly worse in patients with fatty livers (P <.05), including serious morbidity (32% vs 24%), postoperative invasive biliary procedures (15% vs 10%), organ space infections (11% vs 7.8%), and pulmonary complications. Patients with fatty livers and the metabolic syndrome had significantly increased postoperative cardiac arrests, pulmonary embolisms, and mortality (P < .05). CONCLUSION Fatty liver disease is associated with significantly worse outcomes after major hepatectomy. The metabolic syndrome confers an increased risk of postoperative mortality.
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Affiliation(s)
| | - Henry A Pitt
- Department of Surgery, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ
| | - Ambria S Moten
- Department of Surgery, Temple University Hospital, Philadelphia, PA
| | | | - Antonio Di Carlo
- Department of Surgery, Temple University Hospital, Philadelphia, PA
| | - Kwan N Lau
- Department of Surgery, Temple University Hospital, Philadelphia, PA.
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29
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Brüggenwirth IMA, van Reeven M, Vasiliauskaitė I, van der Helm D, van Hoek B, Schaapherder AF, Alwayn IPJ, van den Berg AP, de Meijer VE, Darwish Murad S, Polak WG, Porte RJ. Donor diabetes mellitus is a risk factor for diminished outcome after liver transplantation: a nationwide retrospective cohort study. Transpl Int 2020; 34:110-117. [PMID: 33067844 PMCID: PMC7820994 DOI: 10.1111/tri.13770] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2020] [Revised: 07/09/2020] [Accepted: 10/11/2020] [Indexed: 12/15/2022]
Abstract
With the growing incidence of diabetes mellitus (DM), an increasing number of organ donors with DM can be expected. We sought to investigate the association between donor DM with early post‐transplant outcomes. From a national cohort of adult liver transplant recipients (1996–2016), all recipients transplanted with a liver from a DM donor (n = 69) were matched 1:2 with recipients of livers from non‐DM donors (n = 138). The primary end‐point included early post‐transplant outcome, such as the incidence of primary nonfunction (PNF), hepatic artery thrombosis (HAT), and 90‐day graft survival. Cox regression analysis was used to analyze the impact of donor DM on graft failure. PNF was observed in 5.8% of grafts from DM donors versus 2.9% of non‐DM donor grafts (P = 0.31). Recipients of grafts derived from DM donors had a higher incidence of HAT (8.7% vs. 2.2%, P = 0.03) and decreased 90‐day graft survival (88.4% [70.9–91.1] vs. 96.4% [89.6–97.8], P = 0.03) compared to recipients of grafts from non‐DM donors. The adjusted hazard ratio for donor DM on graft survival was 2.21 (1.08–4.53, P = 0.03). In conclusion, donor DM is associated with diminished outcome early after liver transplantation. The increased incidence of HAT after transplantation of livers from DM donors requires further research.
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Affiliation(s)
- Isabel M A Brüggenwirth
- Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Marjolein van Reeven
- Department of Surgery, Division of Hepatopancreatobiliary and Transplant Surgery, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Indrė Vasiliauskaitė
- Department of Surgery, Division of Hepatopancreatobiliary and Transplant Surgery, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Danny van der Helm
- Department of Gastroenterology and Hepatology, Transplantation Center, Leiden University Medical Center, Leiden University, Leiden, The Netherlands
| | - Bart van Hoek
- Department of Gastroenterology and Hepatology, Transplantation Center, Leiden University Medical Center, Leiden University, Leiden, The Netherlands.,Department of Surgery, Leiden University Medical Center, Leiden University, Leiden, The Netherlands
| | - Alexander F Schaapherder
- Department of Surgery, Leiden University Medical Center, Leiden University, Leiden, The Netherlands
| | - Ian P J Alwayn
- Department of Gastroenterology and Hepatology, Transplantation Center, Leiden University Medical Center, Leiden University, Leiden, The Netherlands.,Department of Surgery, Leiden University Medical Center, Leiden University, Leiden, The Netherlands
| | - Aad P van den Berg
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Vincent E de Meijer
- Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Sarwa Darwish Murad
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Wojciech G Polak
- Department of Surgery, Division of Hepatopancreatobiliary and Transplant Surgery, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Robert J Porte
- Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
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30
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METİN O, ŞİMŞEK C, GÜRAKAR A. Update on liver transplantation-newer aspects. Turk J Med Sci 2020; 50:1642-1650. [PMID: 32222125 PMCID: PMC7672347 DOI: 10.3906/sag-2002-17] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Accepted: 03/22/2020] [Indexed: 12/12/2022] Open
Abstract
Liver transplantation (LT) remains the only therapeutic option offering gold standard treatment for end-stage liver disease (ESLD) and acute liver failure (ALF), as well as for certain early-stage liver tumors. Currently, the greatest challenge facing LT is the simple fact that there are not enough adequate livers for all the potential patients that could benefit from LT. Despite efforts to expand the donor pool to include living and deceased donors, organ shortage is still a major problem in many countries. To solve this problem, the use of marginal liver grafts has become an inevitable choice. Although the definition of marginal grafts or criteria for expanded donor selection has not been clarified yet, they are usually defined as grafts that may potentially cause primary nonfunction, impaired function, or late loss of function. These include steatotic livers, older donors, donors with positive viral serology, split livers, and donation after cardiac death (DCD). Therefore, to get the best outcome from these liver grafts, donor-recipient selection should be vigilant. Alcohol- related liver disease (ALD) is one of the most common indications for LT in Europe and North America. Traditionally, LT for alcoholic liver disease was kept limited for patients who have achieved 6 months of abstinence, in part due to social and ethical concerns regarding the use of a limited resource. However, the majority of patients with severe alcoholic hepatitis who fail medical therapy will not live long enough to meet this requirement. Besides, the initial results of early liver transplantation (ELT) without waiting for 6 months of abstinence period are satisfactory in severe alcoholic hepatitis (SAH). It will be important to take care of these patients from a newer perspective.
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Affiliation(s)
- Olga METİN
- Department of Internal Medicine, Okmeydanı Training and Research Hospital, İstanbulTurkey
| | - Cem ŞİMŞEK
- Department of Gastroenterology, School of Medicine, Hacettepe University, AnkaraTurkey
| | - Ahmet GÜRAKAR
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine Liver Transplant Program Baltimore, MarylandUSA
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31
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Baidya R, Crawford DHG, Gautheron J, Wang H, Bridle KR. Necroptosis in Hepatosteatotic Ischaemia-Reperfusion Injury. Int J Mol Sci 2020; 21:ijms21165931. [PMID: 32824744 PMCID: PMC7460692 DOI: 10.3390/ijms21165931] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 08/12/2020] [Accepted: 08/12/2020] [Indexed: 02/07/2023] Open
Abstract
While liver transplantation remains the sole treatment option for patients with end-stage liver disease, there are numerous limitations to liver transplantation including the scarcity of donor livers and a rise in livers that are unsuitable to transplant such as those with excess steatosis. Fatty livers are susceptible to ischaemia-reperfusion (IR) injury during transplantation and IR injury results in primary graft non-function, graft failure and mortality. Recent studies have described new cell death pathways which differ from the traditional apoptotic pathway. Necroptosis, a regulated form of cell death, has been associated with hepatic IR injury. Receptor-interacting protein kinase 3 (RIPK3) and mixed-lineage kinase domain-like pseudokinase (MLKL) are thought to be instrumental in the execution of necroptosis. The study of hepatic necroptosis and potential therapeutic approaches to attenuate IR injury will be a key factor in improving our knowledge regarding liver transplantation with fatty donor livers. In this review, we focus on the effect of hepatic steatosis during liver transplantation as well as molecular mechanisms of necroptosis and its involvement during liver IR injury. We also discuss the immune responses triggered during necroptosis and examine the utility of necroptosis inhibitors as potential therapeutic approaches to alleviate IR injury.
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Affiliation(s)
- Raji Baidya
- Faculty of Medicine, The University of Queensland, Brisbane, Queensland QLD 4006, Australia; (R.B.); (D.H.G.C.)
- Gallipoli Medical Research Institute, Brisbane, Queensland QLD 4120, Australia;
| | - Darrell H. G. Crawford
- Faculty of Medicine, The University of Queensland, Brisbane, Queensland QLD 4006, Australia; (R.B.); (D.H.G.C.)
- Gallipoli Medical Research Institute, Brisbane, Queensland QLD 4120, Australia;
| | - Jérémie Gautheron
- Sorbonne University, Inserm, Centre de Recherche Saint-Antoine (CRSA), 75012 Paris, France;
- Institute of Cardiometabolism and Nutrition (ICAN), 75013 Paris, France
| | - Haolu Wang
- Gallipoli Medical Research Institute, Brisbane, Queensland QLD 4120, Australia;
- Diamantina Institute, The University of Queensland, Brisbane, Queensland QLD 4102, Australia
| | - Kim R. Bridle
- Faculty of Medicine, The University of Queensland, Brisbane, Queensland QLD 4006, Australia; (R.B.); (D.H.G.C.)
- Gallipoli Medical Research Institute, Brisbane, Queensland QLD 4120, Australia;
- Correspondence: ; Tel.: +61-7-3346-0698
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32
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Savic D, Hodson L, Neubauer S, Pavlides M. The Importance of the Fatty Acid Transporter L-Carnitine in Non-Alcoholic Fatty Liver Disease (NAFLD). Nutrients 2020; 12:E2178. [PMID: 32708036 PMCID: PMC7469009 DOI: 10.3390/nu12082178] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Revised: 07/17/2020] [Accepted: 07/20/2020] [Indexed: 12/16/2022] Open
Abstract
L-carnitine transports fatty acids into the mitochondria for oxidation and also buffers excess acetyl-CoA away from the mitochondria. Thus, L-carnitine may play a key role in maintaining liver function, by its effect on lipid metabolism. The importance of L-carnitine in liver health is supported by the observation that patients with primary carnitine deficiency (PCD) can present with fatty liver disease, which could be due to low levels of intrahepatic and serum levels of L-carnitine. Furthermore, studies suggest that supplementation with L-carnitine may reduce liver fat and the liver enzymes alanine aminotransferase (ALT) and aspartate transaminase (AST) in patients with Non-Alcoholic Fatty Liver Disease (NAFLD). L-carnitine has also been shown to improve insulin sensitivity and elevate pyruvate dehydrogenase (PDH) flux. Studies that show reduced intrahepatic fat and reduced liver enzymes after L-carnitine supplementation suggest that L-carnitine might be a promising supplement to improve or delay the progression of NAFLD.
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Affiliation(s)
- Dragana Savic
- Radcliffe Department of Medicine, Oxford Centre for Magnetic Resonance Research, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK; (S.N.); (M.P.)
| | - Leanne Hodson
- Radcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology & Metabolism, Churchill Hospital, University of Oxford, Oxford OX3 7LE, UK;
- Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford OX3 7LE, UK
| | - Stefan Neubauer
- Radcliffe Department of Medicine, Oxford Centre for Magnetic Resonance Research, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK; (S.N.); (M.P.)
| | - Michael Pavlides
- Radcliffe Department of Medicine, Oxford Centre for Magnetic Resonance Research, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK; (S.N.); (M.P.)
- Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford OX3 7LE, UK
- Translational Gastroenterology Unit, University of Oxford, Oxford OX3 9DU, UK
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33
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Chung JH, Ryu JH, Yang KH, Choi BH, Park Y, Lee TB, Shim JR, Ko HJ, Cho SH. Efficacy and Safety of Weight Reduction of the Donor in Hepatic Steatosis for Living Donor Liver Transplantation. Ann Transplant 2020; 25:e923211. [PMID: 32690857 PMCID: PMC7393957 DOI: 10.12659/aot.923211] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Background Use of steatotic livers is a known risk factor for increased primary nonfunction after liver transplantation. This study investigated the efficacy and clinical outcome of simple weight reduction of steatosis for donors undergoing living-donor liver transplantation (LDLT). Material/Methods We defined two groups: the reduction group, which included donors with >30% macrovesicular steatosis and body mass index (BMI) >25 kg/m2, and the conventional group, which included donors with <30% macrovesicular steatosis. Donors in the reduction group were educated about the goal of voluntary weight reduction to lose 5% of body weight, not exceeding 1.6 kg/week, and attempted to maintain weight reduction for at least 8 weeks. Results Weight reduction significantly improved steatosis (40.71±14.56 vs. 7.867±2.67, p=0.000). Body weight and BMI were reduced in the weight reduction group (85.40±8.254 kg vs. 76.27±7.556 kg, p=0.052; and 28.89±2.303 kg/m2vs. 26.16±1.629 kg/m2, p=0.025, respectively). The transplanted grafts of recipients and remnant livers of donors showed intact liver function, and there was no difference in liver function tests between the conventional and reduction groups. No significant difference in graft survival was observed. Conclusions Simple weight reduction improves steatosis and contributes to safer LDLT for both recipient and donor. Importantly, according to our results, even steatotic livers can be used for LDLT after patients follow a simple weight reduction protocol.
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Affiliation(s)
- Jae Hun Chung
- Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, South Korea
| | - Je Ho Ryu
- Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, South Korea.,Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, South Korea.,Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, South Korea
| | - Kwang Ho Yang
- Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, South Korea.,Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, South Korea
| | - Byung Hyun Choi
- Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, South Korea.,Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, South Korea
| | - Youngmok Park
- Department of Surgery, Pusan National University Hospital, Yangsan, South Korea.,Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Pusan National University Hospital, Yangsan, South Korea
| | - Tae Beom Lee
- Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, South Korea.,Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, South Korea
| | - Jae Ryong Shim
- Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, South Korea.,Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, South Korea
| | - Hyo Jung Ko
- Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, South Korea.,Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, South Korea
| | - Sung Hwan Cho
- Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, South Korea.,Division of Colorectal Surgery and Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, South Korea
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Abstract
PURPOSE OF REVIEW As experience grows, living donor liver transplantation (LDLT) has become an effective treatment option to overcome the deceased donor organ shortage. RECENT FINDINGS Donor safety is the highest priority in LDLT. Strict donor selection according to structured protocols and center experience are the main factors that determine donor safety. However, with increased experience, many centers have explored increasing organ availability within living donation by means of ABO incompatible LDLT, dual graft LDLT, and anonymous living donation. Also, this growing experience in LDLT has allowed the transplant community to cautiously explore the role of liver transplantation for hepatocellular carcinoma outside of Milan criteria and patients with unresectable colorectal liver metastases. SUMMARY LDLT has become established as a viable strategy to ameliorate the organ shortage experienced by centers around the world. Improved understanding of this technique has allowed the improved utilization of live donor graft resources, without compromising donor safety. Moreover, LDLT may offer some advantages over deceased donor liver transplantation and a unique opportunity to assess the broader applicability of liver transplantation.
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35
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Safe Use of Right Lobe Live Donor Livers With up to 20% Macrovesicular Steatosis Without Compromising Donor Safety and Recipient Outcome. Transplantation 2020; 104:308-316. [DOI: 10.1097/tp.0000000000002847] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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36
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Preoperative 5-aminolevulinic acid administration for brain tumor surgery is associated with an increase in postoperative liver enzymes: a retrospective cohort study. Acta Neurochir (Wien) 2019; 161:2289-2298. [PMID: 31473825 DOI: 10.1007/s00701-019-04053-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Accepted: 08/22/2019] [Indexed: 12/27/2022]
Abstract
BACKGROUND Besides 5-aminolevulinic acid (5-ALA), liver enzyme elevation after brain tumor surgery can be caused by anesthesia and medications. In this retrospective study, we determined whether preoperative 5-ALA administration is associated with postoperative elevation of liver enzymes (PELE) in brain tumor patients and identified predictive factors for PELE in patients treated with 5-ALA. METHODS In 179 patients undergoing brain tumor surgery with preoperative normal values of liver enzymes, laboratory data on serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and total bilirubin (T.bil) levels were collected preoperatively and through postoperative day (POD) 45. RESULTS Ninety-nine PELEs (ALT, 56; AST, 34; ALP, 5; and TB, 4) were observed in 62 (34.6%) patients. Four (4.2%) patients treated with 5-ALA showed grade 3 elevation of transaminases based on the Common Terminology Criteria for Adverse Effects. Preoperative 5-ALA treatment was predictive of PELE (odds ratio [95% confidence interval], 2.30 [1.14-4.67]; P = 0.021). In patients treated with 5-ALA (n = 95), 70 PELEs (ALT, 39; AST, 22; ALP, 5; and TB, 4) were observed in 41 (43.2%) patients and significant predictive factors for PELE were preoperative ALT level (1.10 [1.04-1.17]; P = 0.001) and body mass index (BMI, 1.29 [1.08-1.56]; P = 0.006). In patients treated with 5-ALA, 13 and 36 patients, of 39 patients whose maximum postoperative ALT levels > 40 U/L, showed the normal value of serum ALT on PODs 14 and 45, respectively. Only three patients showed ALT elevation > 40 U/L on PODs 15-45, with a downward trend. CONCLUSIONS The use of 5-ALA for brain tumor surgery in patients with preoperative normal values of liver enzymes was associated with increased transient PELE, but a low incidence of severely elevated liver transaminases levels. When 5-ALA is administered to patients with the upper normal value of preoperative serum ALT and overweight, attention is paid to PELE.
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37
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Jiménez-Castro MB, Cornide-Petronio ME, Gracia-Sancho J, Peralta C. Inflammasome-Mediated Inflammation in Liver Ischemia-Reperfusion Injury. Cells 2019; 8:1131. [PMID: 31547621 PMCID: PMC6829519 DOI: 10.3390/cells8101131] [Citation(s) in RCA: 166] [Impact Index Per Article: 27.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Revised: 09/19/2019] [Accepted: 09/21/2019] [Indexed: 12/16/2022] Open
Abstract
Ischemia-reperfusion injury is an important cause of liver damage occurring during surgical procedures including hepatic resection and liver transplantation, and represents the main underlying cause of graft dysfunction and liver failure post-transplantation. To date, ischemia-reperfusion injury is an unsolved problem in clinical practice. In this context, inflammasome activation, recently described during ischemia-reperfusion injury, might be a potential therapeutic target to mitigate the clinical problems associated with liver transplantation and hepatic resections. The present review aims to summarize the current knowledge in inflammasome-mediated inflammation, describing the experimental models used to understand the molecular mechanisms of inflammasome in liver ischemia-reperfusion injury. In addition, a clear distinction between steatotic and non-steatotic livers and between warm and cold ischemia-reperfusion injury will be discussed. Finally, the most updated therapeutic strategies, as well as some of the scientific controversies in the field will be described. Such information may be useful to guide the design of better experimental models, as well as the effective therapeutic strategies in liver surgery and transplantation that can succeed in achieving its clinical application.
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Affiliation(s)
| | | | - Jordi Gracia-Sancho
- Liver Vascular Biology Research Group, Barcelona Hepatic Hemodynamic Laboratory IDIBAPS, 08036 Barcelona, Spain.
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 08036 Barcelona, Spain.
| | - Carmen Peralta
- Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain.
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 08036 Barcelona, Spain.
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38
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Somovilla-Gómez F, Lostado-Lorza R, Corral-Bobadilla M, Escribano-García R. Improvement in determining the risk of damage to the human lumbar functional spinal unit considering age, height, weight and sex using a combination of FEM and RSM. Biomech Model Mechanobiol 2019; 19:351-387. [DOI: 10.1007/s10237-019-01215-4] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2019] [Accepted: 08/17/2019] [Indexed: 11/24/2022]
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39
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Adalı G, Bozkurt B, Ceyhan Ö, Server S, Doğusoy GB, Yüzer Y, Tokat Y. Body Mass Index and Unenhanced CT as a Predictor of Hepatic Steatosis in Potential Liver Donors. Transplant Proc 2019; 51:2373-2378. [PMID: 31402250 DOI: 10.1016/j.transproceed.2019.02.047] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Accepted: 02/17/2019] [Indexed: 12/23/2022]
Abstract
BACKGROUND In living-donor liver transplantation, donor hepatic steatosis is crucial for both the donor and the recipient. Body mass index (BMI) and the unenhanced computed tomography liver attenuation index (CT LAI) are noninvasive methods to predict hepatic steatosis in living-donor liver candidates. AIM To analyze the diagnostic accuracy of CT LAI in conjunction with different BMI values for macrovesicular steatosis in living-donor liver candidates. METHODS A total of 264 potential liver donors were included. The diagnostic accuracy of 2 CT LAI cut-offs and 3 BMI cut-off values for the assessment of hepatic steatosis ≥15% and ≤5% was determined. RESULTS Using CT LAI, the area under the receiver operating characteristic curve was 0.97 (95% CI = 0.89-0.99) for hepatic steatosis ≥15% in donors with BMI <25 kg/m2. For detecting hepatic steatosis ≥15%, a CT LAI ≤0 had specificities of 100%, 76.2%, and 55.6% and positive predictive values of 100%, 95.5%, and 93.5% for patients with BMI values <25 kg/m2, 25 to 29.9 kg/m2, and ≥30 kg/m2, respectively. According to logistic regression analyses, only CT LAI ≤0 was found to be independently associated with hepatic steatosis ≥15%. CONCLUSIONS In donors with BMI <30 kg/m2 and a CT LAI value >6, liver biopsy might be avoided. Biopsy may be reserved solely for donors with CT LAI value >0 and BMI ≥30 kg/m2 as the diagnostic accuracy of computed tomography for predicting hepatic steatosis decreases with increasing BMI.
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Affiliation(s)
- Gupse Adalı
- Department of Gastroenterology, Istanbul Bilim University, Florence Nightingale Hospital Liver Unit, Istanbul, Turkey.
| | - Birkan Bozkurt
- Department of General Surgery, Istanbul Bilim University, Florence Nightingale Hospital Liver Unit, Istanbul, Turkey
| | - Özgür Ceyhan
- Department of Radiology, Istanbul Bilim University, Istanbul, Turkey
| | - Sadık Server
- Department of Radiology, Istanbul Bilim University, Istanbul, Turkey
| | | | - Yıldıray Yüzer
- Department of General Surgery, Istanbul Bilim University, Florence Nightingale Hospital Liver Unit, Istanbul, Turkey
| | - Yaman Tokat
- Department of General Surgery, Istanbul Bilim University, Florence Nightingale Hospital Liver Unit, Istanbul, Turkey
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40
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Bae JS, Lee DH, Lee JY, Kim H, Yu SJ, Lee JH, Cho EJ, Lee YB, Han JK, Choi BI. Assessment of hepatic steatosis by using attenuation imaging: a quantitative, easy-to-perform ultrasound technique. Eur Radiol 2019; 29:6499-6507. [PMID: 31175413 DOI: 10.1007/s00330-019-06272-y] [Citation(s) in RCA: 108] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Revised: 05/02/2019] [Accepted: 05/10/2019] [Indexed: 12/14/2022]
Abstract
OBJECTIVES To evaluate the diagnostic performance of attenuation imaging (ATI) in the detection of hepatic steatosis compared with a histopathology gold standard. METHODS We prospectively enrolled 108 consecutive patients (35 males; median age, 54.0 years) who underwent percutaneous liver biopsy for evaluation of diffuse liver disease between January 2018 and November 2018 in a tertiary academic center. Grayscale ultrasound examination with ATI was performed just before biopsy, and an attenuation coefficient (AC) was obtained from each patient. The degree of hepatic steatosis, fibrosis stage, and necroinflammatory activity were assessed on histopathologic examination. The significant factor associated with the AC was found by a linear regression analysis, and the diagnostic performance of the AC for the classification into each hepatic steatosis stage was evaluated by receiver operating characteristic (ROC) analysis. RESULTS The distribution of hepatic steatosis grade on histopathology was 53/11/22/16/6 for none/mild (< 10%)/mild (≥ 10%)/moderate/severe steatosis, respectively. The area under the ROC curve, sensitivity, specificity, and optimal cutoff AC value for detection of hepatic steatosis ranged from 0.843-0.926, 74.5-100.0%, 77.4-82.8%, and 0.635-0.745, respectively. Multivariate analysis revealed that the degree of steatosis was the only significant determinant factor for the AC. CONCLUSIONS The AC from ATI provided good diagnostic performance in detecting the varying degrees of hepatic steatosis. The degree of steatosis was the only significant factor affecting the AC, whereas fibrosis and inflammation were not. KEY POINTS • Attenuation imaging (ATI) is based on two-dimensional grayscale ultrasound images that can incorporate into routine ultrasound examinations with less than 2 min of acquisition time. • ATI provided good diagnostic performance in detecting the varying degrees of hepatic steatosis with an area under the ROC curves ranging from 0.843 to 0.926, and there was no technical failure in this study indicating high applicability of this technique. • The degree of hepatic steatosis was the only significant factor affecting the result of ATI examination.
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Affiliation(s)
- Jae Seok Bae
- Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.,Department of Radiology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Dong Ho Lee
- Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea. .,Department of Radiology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
| | - Jae Young Lee
- Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.,Department of Radiology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.,Institute of Radiation Medicine, Seoul National University Medical Research Center, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Haeryoung Kim
- Department of Pathology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Su Jong Yu
- Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Eun Ju Cho
- Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Yun Bin Lee
- Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Joon Koo Han
- Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.,Department of Radiology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.,Institute of Radiation Medicine, Seoul National University Medical Research Center, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Byung Ihn Choi
- Department of Radiology, Chung-Ang University Hospital, 102, Heukseok-ro, Dongjak-gu, Seoul, 06973, Republic of Korea
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Regional Variation in Utilization and Outcomes of Liver Allografts From Donors With High Body Mass Index and Graft Macrosteatosis: A Role for Liver Biopsy. Transplantation 2019; 103:122-130. [PMID: 30048394 DOI: 10.1097/tp.0000000000002379] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
BACKGROUND Obesity, defined as a high body mass index (hBMI) of 30 kg/m or greater, is a growing epidemic worldwide and is associated with multiple comorbidities. High BMI individuals account for an increasing portion of potential liver donors. Here we evaluate trends in the utilization and outcomes of hBMI donors on a national and regional level and the potential role of liver biopsy in donor evaluation. METHODS United Network for Organ Sharing Standard Transplant Analysis and Research database was evaluated for deceased donor liver transplants between 2006 and 2016 across 11 Organ Procurement and Transplantation Network regions. High BMI donors were compared with lower BMI counterparts and evaluated for biopsy rates, utilization rates and allograft outcomes. Univariate and multivariable analyses were performed. RESULTS Seventy-seven thousand fifty potential donors were identified and 60 200 transplants were evaluated. Utilization rates for hBMI donors were 66.1% versus 78.1% for lower BMI donors (P < 0.001). Pretransplant biopsy was performed more frequently in hBMI donors (52.1% vs 33.1%, P < 0.001) and macrosteatosis of 30% or greater was identified more often (21.1% vs 12.2%, P < 0.001). Biopsy performance increased utilization rate of hBMI donors in 7 of 11 Organ Procurement and Transplantation Network regions. region 6 showed the highest rate of biopsy performance, high rate of hBMI donor utilization, and highest 5-year estimated graft survival rates of all regions. CONCLUSIONS High BMI donors have not previously been associated with worse graft survival in multivariable analyses; however, they are used much less frequently. Liver biopsy may increase the utilization rate of hBMI donors and improve donor selection. Further evaluation of regions with high rates of utilization and good outcomes is warranted.
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42
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International Liver Transplantation Consensus Statement on End-stage Liver Disease Due to Nonalcoholic Steatohepatitis and Liver Transplantation. Transplantation 2019; 103:45-56. [PMID: 30153225 DOI: 10.1097/tp.0000000000002433] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Nonalcoholic steatohepatitis (NASH)-related cirrhosis has become one of the most common indications for liver transplantation (LT), particularly in candidates older than 65 years. Typically, NASH candidates have concurrent obesity, metabolic, and cardiovascular risks, which directly impact patient evaluation and selection, waitlist morbidity and mortality, and eventually posttransplant outcomes. The purpose of these guidelines is to highlight specific features commonly observed in NASH candidates and strategies to optimize pretransplant evaluation and waitlist survival. More specifically, the working group addressed the following clinically relevant questions providing recommendations based on the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system supported by rigorous systematic reviews and consensus: (1) Is the outcome after LT similar to that of other etiologies of liver disease? (2) Is the natural history of NASH-related cirrhosis different from other etiologies of end-stage liver disease? (3) How should cardiovascular risk be assessed in the candidate for LT? Should the assessment differ from that done in other etiologies? (4) How should comorbidities (hypertension, diabetes, dyslipidemia, obesity, renal dysfunction, etc.) be treated in the candidate for LT? Should treatment and monitoring of these comorbidities differ from that applied in other etiologies? (5) What are the therapeutic strategies recommended to improve the cardiovascular and nutritional status of a NASH patient in the waiting list for LT? (6) Is there any circumstance where obesity should contraindicate LT? (7) What is the optimal time for bariatric surgery: before, during, or after LT? (8) How relevant is donor steatosis for LT in NASH patients?
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43
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Endo Y, Ohta M, Tada K, Nakanuma H, Saga K, Masuda T, Hirashita T, Iwashita Y, Ozeki Y, Masaki T, Inomata M. Improvement of non-alcoholic fatty liver disease after laparoscopic sleeve gastrectomy in Japanese obese patients. Ann Gastroenterol Surg 2019; 3:285-290. [PMID: 31131357 PMCID: PMC6524101 DOI: 10.1002/ags3.12234] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2018] [Revised: 12/27/2018] [Accepted: 01/06/2019] [Indexed: 01/12/2023] Open
Abstract
PURPOSE The purpose of this study was to evaluate changes in non-alcoholic fatty liver disease (NAFLD) after laparoscopic sleeve gastrectomy (LSG) using computed tomography (CT) images. METHODS We analyzed data from 57 patients who underwent LSG and had CTs performed before and after surgery. The patients included 34 women and 23 men (with an average age of 43 years); their mean preoperative weight and body mass index were 120 kg and 46 kg/m2, respectively. Obesity-related health disorders included type 2 diabetes mellitus (T2DM) in 33 patients, hypertension in 33 and dyslipidemia in 32. We diagnosed NAFLD in cases with liver to spleen ratios (L/S ratio) <0.9 on non-contrast CT images. We evaluated changes in body weights, BMIs, comorbidities, metabolic parameters, L/S ratios, and liver volumes after surgery. RESULTS The mean interval between CT scans before and after surgery was 26 months. The total weight loss and % excess weight loss were 35 kg and 72%, respectively. The remission rates for T2DM, hypertension, and dyslipidemia were 85%, 76% and 84%, respectively. After LSG, the L/S ratio increased in all the patients, while all except for one had L/S ratio >0.9. We diagnosed 33 out of 57 patients (58%) as having NAFLD before the operation. After the operation, the L/S ratios and liver volumes were not statistically different between the patients with previous NAFLD and those without it. CONCLUSION Laparoscopic sleeve gastrectomy is an effective treatment for obesity-related health disorders including NAFLD in Japanese obese patients.
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Affiliation(s)
- Yuichi Endo
- Department of Gastroenterological and Pediatric SurgeryOita University Faculty of MedicineOitaJapan
| | - Masayuki Ohta
- Department of Gastroenterological and Pediatric SurgeryOita University Faculty of MedicineOitaJapan
| | - Kazuhiro Tada
- Department of Gastroenterological and Pediatric SurgeryOita University Faculty of MedicineOitaJapan
| | - Hiroaki Nakanuma
- Department of Gastroenterological and Pediatric SurgeryOita University Faculty of MedicineOitaJapan
| | - Kunihiro Saga
- Department of Gastroenterological and Pediatric SurgeryOita University Faculty of MedicineOitaJapan
| | - Takashi Masuda
- Department of Gastroenterological and Pediatric SurgeryOita University Faculty of MedicineOitaJapan
| | - Teijiro Hirashita
- Department of Gastroenterological and Pediatric SurgeryOita University Faculty of MedicineOitaJapan
| | - Yukio Iwashita
- Department of Gastroenterological and Pediatric SurgeryOita University Faculty of MedicineOitaJapan
| | - Yoshinori Ozeki
- Department of Endocrinology, Metabolism, Rheumatology and NephrologyOita University Faculty of MedicineOitaJapan
| | - Takayuki Masaki
- Department of Endocrinology, Metabolism, Rheumatology and NephrologyOita University Faculty of MedicineOitaJapan
| | - Masafumi Inomata
- Department of Gastroenterological and Pediatric SurgeryOita University Faculty of MedicineOitaJapan
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44
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Álvarez-Mercado AI, Gulfo J, Romero Gómez M, Jiménez-Castro MB, Gracia-Sancho J, Peralta C. Use of Steatotic Grafts in Liver Transplantation: Current Status. Liver Transpl 2019; 25:771-786. [PMID: 30740859 DOI: 10.1002/lt.25430] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Accepted: 02/02/2019] [Indexed: 12/12/2022]
Abstract
In the field of liver transplantation, the demand for adequate allografts greatly exceeds the supply. Therefore, expanding the donor pool to match the growing demand is mandatory. The present review summarizes current knowledge of the pathophysiology of ischemia/reperfusion injury in steatotic grafts, together with recent pharmacological approaches aimed at maximizing the utilization of these livers for transplantation. We also describe the preclinical models currently available to understand the molecular mechanisms controlling graft viability in this specific type of donor, critically discussing the heterogeneity in animal models, surgical methodology, and therapeutic interventions. This lack of common approaches and interventions makes it difficult to establish the pathways involved and the relevance of isolated discoveries, as well as their transferability to clinical practice. Finally, we discuss how new therapeutic strategies developed from experimental studies are promising but that further studies are warranted to translate them to the bedside.
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Affiliation(s)
- Ana I Álvarez-Mercado
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - José Gulfo
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Manuel Romero Gómez
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas (CIBEREHD), Madrid, Spain
- Inter-Centre Unit of Digestive Diseases, Virgen del Rocio University Hospitals, Sevilla, Spain; Institute of Biomedicine of Seville, Seville, Spain
- Institute of Biomedicine of Seville, Seville, Spain
| | | | - Jordi Gracia-Sancho
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas (CIBEREHD), Madrid, Spain
- Hepatology, Department of Biomedical Research, University of Bern, Bern, Switzerland
| | - Carmen Peralta
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas (CIBEREHD), Madrid, Spain
- Universidad Internacional de Cataluña, Barcelona, Spain
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45
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Croome KP, Lee DD, Taner CB. The "Skinny" on Assessment and Utilization of Steatotic Liver Grafts: A Systematic Review. Liver Transpl 2019; 25:488-499. [PMID: 30817859 DOI: 10.1002/lt.25408] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2018] [Accepted: 12/25/2018] [Indexed: 02/07/2023]
Abstract
The frequency at which steatotic deceased donor liver grafts are encountered will likely continue to increase. Utilization of liver grafts with moderate-to-severe steatosis for liver transplantation (LT) has been previously shown to be associated with increased rates of primary nonfunction and decreased recipient survival. In order to better inform clinical decision making and guide future research, critical evaluation of the literature on donor liver steatosis and posttransplantation outcome is needed. This literature review aims to provide the "skinny" on using deceased donor steatotic livers for LT.
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Affiliation(s)
| | - David D Lee
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
| | - C Burcin Taner
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
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46
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Cesaretti M, Addeo P, Schiavo L, Anty R, Iannelli A. Assessment of Liver Graft Steatosis: Where Do We Stand? Liver Transpl 2019; 25:500-509. [PMID: 30380197 DOI: 10.1002/lt.25379] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2018] [Accepted: 10/28/2018] [Indexed: 12/14/2022]
Abstract
The growing number of patients on waiting lists for liver transplantation and the shortage of organs have forced many centers to adopt extended criteria for graft selection, moving the limit of acceptance for marginal livers. Steatotic grafts that were, in the past, considered strictly unacceptable for transplantation because of the high risk of early nonfunction are now considered as a potential resource for organ implementation. Several methods to diagnose, measure, classify, and stage steatosis exist, but none can be considered qualitatively and quantitatively "the ideal method" to date. Clinical, biological, and imaging data can be very helpful to estimate graft steatosis, but histology still remains the gold standard. There is an increasing need for rapid and reliable tools to assess graft steatosis. Herein, we present a comprehensive review of the approaches that are currently used to quantify steatosis in liver grafts.
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Affiliation(s)
- Manuela Cesaretti
- Department of HPB Surgery and Liver Transplantation, Hôpital Beaujon, AP-HP, Clichy, France.,Department of Nanophysics, Italian Institute of Technology, Genova, Italy
| | - Pietro Addeo
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Pôle des Pathologies Digestives, Hépatiques et de la Transplantation, Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, Strasbourg, France
| | - Luigi Schiavo
- Department of Cardio-Thoracic and Respiratory Science, University of Campania "Luigi Vanvitelli," Naples, Italy.,IX Division of General Surgery, Vascular Surgery and Applied Biotechnology, Naples University Policlinic, Naples, Italy
| | - Rodolphe Anty
- Faculty of Medicine, University of Nice-Sophia Antipolis, Nice, France.,INSERM, U1065, Team 8 "Hepatic complications in obesity," Nice, France.,Centre Hospitalier Universitaire Nice, Digestive Center, Nice, France
| | - Antonio Iannelli
- Faculty of Medicine, University of Nice-Sophia Antipolis, Nice, France.,Digestive Unit, Archet 2 Hospital, University Hospital of Nice, Nice, France
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47
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Weta IW, Mahadewa TGB, Sutirtayasa WP, Subawa A, Sitanggang FP, Widyadharma IPE. The Comparison of Simple Anthropometric and Biochemical Parameters for Predicting Liver Steatosis in Obese Balinese Young Women. Open Access Maced J Med Sci 2018; 6:2062-2066. [PMID: 30559861 PMCID: PMC6290413 DOI: 10.3889/oamjms.2018.449] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Revised: 10/21/2018] [Accepted: 10/24/2018] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND: The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing globally. Early identification of liver steatosis (LS) status is critical to prevent the development of NAFLD into non-alcoholic steatohepatitis (NASH) fibrosis. AIM: This study aimed at exploring the validity of simple anthropometric and biochemical parameters to predict LS in young obese women. MATERIALS AND METHODS: This is a cross-sectional study involving 132 young obese women. We collected the data of measured waist circumference (WC), body mass index (BMI), serum triglyceride (TG), and gamma-glutamyltransferase (GGT). The lipid accumulation product (LAP) was designed from TG and WC variables. Fatty liver index (FLI) was calculated from TG, BMI, WC, and GGT variables. LS status was measured using ultrasonography assay. Statistical significance was set at p < 0.05. RESULTS: A positive correlation was found between BMI, WC, TG, GGT, LAP, FLI, and LS (p = 0.001). We found that BMI is a better predictor for LS to WC. Our multiple linear regression analysis revealed that BMI, GGT, and TG could predict 41.4% of LS. The validity (specificity, sensitivity, and odds ratio) of simple body fat parameters in predicting LS were as follows: BMI ≥ 30 kg/m2 (69.6%, 74.4%, and 6.21), WC ≥ 90 cm (67.4%, 70.0%, and 4.28), TG ≥ 100 mg/dL (70.6%, 70.0%, and 5.62) and GGT ≥ 20 μg/L (69.6%, 77.5%, and 7.87), as well as LAP ≥ 30 (82.6%, 70.0%, and 11.1), and FLI ≥ 2.5 (79.3%, 72.5%, and 10.1), significantly. CONCLUSION: Simple anthropometric and biochemical parameters (BMI, WC, and TG, GGT), are appropriately predicting LS as well as LAP, and FLI among obese Balinese young women.
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Affiliation(s)
- I Wayan Weta
- Department of Public Health, Preventive Medicine, and Clinical Nutrition, Faculty of Medicine, Udayana University, Bali, Indonesia
| | | | - Wayan Putu Sutirtayasa
- Department of Clinical Pathology, Faculty of Medicine, Udayana University, Bali, Indonesia
| | - Aan Subawa
- Department of Clinical Pathology, Faculty of Medicine, Udayana University, Bali, Indonesia
| | - Firman P Sitanggang
- Department of Radiology, Faculty of Medicine, Udayana University, Bali, Indonesia
| | - I Putu Eka Widyadharma
- Department of Neurology, Faculty of Medicine, Udayana University, Sanglah General Hospital, Bali, Indonesia
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48
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Goja S, Kumar Yadav S, Singh Soin A. Readdressing the Middle Hepatic Vein in Right Lobe Liver Donation: Triangle of Safety. Liver Transpl 2018; 24:1363-1376. [PMID: 30359489 DOI: 10.1002/lt.25289] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2018] [Revised: 04/30/2018] [Accepted: 05/16/2018] [Indexed: 02/07/2023]
Abstract
For equipoising donor safety and optimal recipient outcomes, we adopted an algorithmic "triangle of safety" approach to retrieve 3 types of right lobe liver grafts (RLGs), namely, the modified extended right lobe graft (MERLG), the partial right lobe graft (PRLG), and the modified right lobe graft (MRLG). Reconstruction to achieve a single wide anterior sector outflow was ensured in all patients. We present donor and recipient outcomes based on our approach in 665 right lobe (RL) living donor liver transplantations (LDLTs) performed from January 2013 to August 2015. There were 347 patients who received a MERLG, 117 who received a PRLG, and 201 who received a MRLG. A right lobe graft (RLG) with a middle hepatic vein was retrieved only in 3 out of 18 donors with steatosis >10%. Cold ischemia time was significantly more and remnant volume was less in the MRLG group. Of the donors, 29.3% had complications (26% Clavien-Dindo grade I, II) with no statistically significant difference among the groups. The Model for End-Stage Liver Disease score was higher in the MERLG group. There were 34 out of 39 with a graft-to-recipient weight ratio (GRWR) of <0.7% who received a MERLG with inflow modulation. Out of 4 patients who developed small-for-size syndrome in this group, 2 died. The 90-day patient survival rate was similar among different GRWRs and types of RLG. In conclusion, a selective and tailored approach for RL donor hepatectomy based on optimal functional volume and metabolic demands not only addresses the key issue of double equipoise in LDLT but also creates a safe path for extending the limits.
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Affiliation(s)
- Sanjay Goja
- Institute of Liver Transplantation and Regenerative Medicine, Medanta-The Medicity, Gurgaon, Delhi, India
| | - Sanjay Kumar Yadav
- Institute of Liver Transplantation and Regenerative Medicine, Medanta-The Medicity, Gurgaon, Delhi, India
| | - Arvinder Singh Soin
- Institute of Liver Transplantation and Regenerative Medicine, Medanta-The Medicity, Gurgaon, Delhi, India
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Lozanovski VJ, Khajeh E, Fonouni H, Pfeiffenberger J, von Haken R, Brenner T, Mieth M, Schirmacher P, Michalski CW, Weiss KH, Büchler MW, Mehrabi A. The impact of major extended donor criteria on graft failure and patient mortality after liver transplantation. Langenbecks Arch Surg 2018; 403:719-731. [PMID: 30112639 DOI: 10.1007/s00423-018-1704-z] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2018] [Accepted: 08/07/2018] [Indexed: 12/20/2022]
Abstract
INTRODUCTION Numerous extended donor criteria (EDC) have been identified in liver transplantation (LT), but different EDC have different impacts on graft and patient survival. This study aimed to identify major EDC (maEDC) that were best able to predict the outcome after LT and to examine the plausibility of an allocation algorithm based on these criteria. METHODS All consecutive LTs between 12/2006 and 03/2014 were included (n = 611). We analyzed the following EDC: donor age > 65 years, body mass index > 30, malignancy and drug abuse history, intensive care unit stay/ventilation > 7 days, aminotransferases > 3 times normal, serum bilirubin > 3 mg/dL, serum Na+ > 165 mmol/L, positive hepatitis serology, biopsy-proven macrovesicular steatosis (BPS) > 40%, and cold ischemia time (CIT) > 14 h. We analyzed hazard risk ratios of graft failure for each EDC and evaluated primary non-function (PNF). In addition, we analyzed 30-day, 90-day, 1-year, and 3-year graft survival. We established low- and high-risk graft (maEDC 0 vs. ≥ 1) and recipient (labMELD < 20 vs. ≥ 20) groups and compared the post-LT outcomes between these groups. RESULTS BPS > 40%, donor age > 65 years, and CIT > 14 h (all p < 0.05) were independent predictors of graft failure and patient mortality and increased PNF, 30-day, 90-day, 1-year, and 3-year graft failure rates. Three-year graft and patient survival decreased in recipients of ≥ 1 maEDC grafts (all p < 0.05) and LT of high-risk grafts into high-risk recipients yielded worse outcomes compared with other groups. CONCLUSION Donor age > 65 years, BPS > 40%, and CIT > 14 h are major EDC that decrease short and 3-year graft survival, and 3-year patient survival. An allocation algorithm based on maEDC and labMELD is therefore plausible.
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Affiliation(s)
- Vladimir J Lozanovski
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - Elias Khajeh
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - Hamidreza Fonouni
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - Jan Pfeiffenberger
- Department of Internal Medicine IV, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany
| | - Rebecca von Haken
- Department of Anesthesiology, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - Thorsten Brenner
- Department of Anesthesiology, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - Markus Mieth
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - Peter Schirmacher
- Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 220/221, 69120, Heidelberg, Germany
| | - Christoph W Michalski
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - Karl Heinz Weiss
- Department of Internal Medicine IV, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany
| | - Markus W Büchler
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany.
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50
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Burra P, Giannini EG, Caraceni P, Ginanni Corradini S, Rendina M, Volpes R, Toniutto P. Specific issues concerning the management of patients on the waiting list and after liver transplantation. Liver Int 2018; 38:1338-1362. [PMID: 29637743 DOI: 10.1111/liv.13755] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2018] [Accepted: 03/27/2018] [Indexed: 02/06/2023]
Abstract
The present document is a second contribution collecting the recommendations of an expert panel of transplant hepatologists appointed by the Italian Association for the Study of the Liver (AISF) concerning the management of certain aspects of liver transplantation, including: the issue of prompt referral; the management of difficult candidates; malnutrition; living related liver transplants; hepatocellular carcinoma; and the role of direct acting antiviral agents before and after transplantation. The statements on each topic were approved by participants at the AISF Transplant Hepatology Expert Meeting organized by the Permanent Liver Transplant Commission in Mondello on 12-13 May 2017. They are graded according to the GRADE grading system.
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Affiliation(s)
- Patrizia Burra
- Multivisceral Transplant Unit, University Hospital, Padova, Italy
| | - Edoardo G Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Ospedale Policlinico San Martino, Genoa, Italy
| | | | | | | | - Riccardo Volpes
- Hepatology and Gastroenterology Unit, ISMETT-IRCCS, Palermo, Italy
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