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Ly M, Lau NS, Dennis C, Chen J, Risbey C, Tan S, Chen R, Wang C, Gorrell MD, McKenzie C, Kench JG, Liu K, McCaughan GW, Crawford M, Pulitano C. Long-term ex situ normothermic machine perfusion allows regeneration of human livers with severe bile duct injury. Am J Transplant 2025; 25:60-71. [PMID: 39059585 DOI: 10.1016/j.ajt.2024.07.019] [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: 04/11/2024] [Revised: 06/28/2024] [Accepted: 07/15/2024] [Indexed: 07/28/2024]
Abstract
Bile duct regeneration is hypothesized to prevent biliary strictures, a leading cause of morbidity after liver transplantation. Assessing the capacity for biliary regeneration may identify grafts as suitable for transplantation that are currently declined, but this has been unfeasible until now. This study used long-term ex situ normothermic machine perfusion (LT-NMP) to assess biliary regeneration. Human livers that were declined for transplantation were perfused at 36 °C for up to 13.5 days. Bile duct biopsies, bile, and perfusate were collected throughout perfusion, which were examined for features of injury and regeneration. Biliary regeneration was defined as new Ki-67-positive biliary epithelium following severe injury. Ten livers were perfused for a median duration of 7.5 days. Severe bile duct injury occurred in all grafts, and biliary regeneration occurred in 70% of grafts. Traditional biomarkers of biliary viability such as bile glucose improved during perfusion but this was not associated with biliary regeneration (P > .05). In contrast, the maintenance of interleukin-6 and vascular endothelial growth factor-A levels in bile was associated with biliary regeneration (P = .017 for both cytokines). This is the first study to demonstrate biliary regeneration during LT-NMP and identify a cytokine signature in bile as a novel biomarker for biliary regeneration during LT-NMP.
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Affiliation(s)
- Mark Ly
- Centre for Organ Assessment Repair and Optimisation, Royal Prince Alfred Hospital, Sydney, Australia; Australian National Liver Transplantation Unit, Royal Prince Alfred Hospital, Sydney, Australia; Centenary Institute, The University of Sydney, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
| | - Ngee-Soon Lau
- Centre for Organ Assessment Repair and Optimisation, Royal Prince Alfred Hospital, Sydney, Australia; Australian National Liver Transplantation Unit, Royal Prince Alfred Hospital, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
| | - Claude Dennis
- Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, Australia
| | - Jinbiao Chen
- Centenary Institute, The University of Sydney, Sydney, Australia
| | - Charles Risbey
- Centre for Organ Assessment Repair and Optimisation, Royal Prince Alfred Hospital, Sydney, Australia; Australian National Liver Transplantation Unit, Royal Prince Alfred Hospital, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
| | - Sarah Tan
- Central Sydney Immunology Laboratory, Royal Prince Alfred Hospital, NSW, Australia
| | - Renfen Chen
- Central Sydney Immunology Laboratory, Royal Prince Alfred Hospital, NSW, Australia
| | - Chuanmin Wang
- Centre for Organ Assessment Repair and Optimisation, Royal Prince Alfred Hospital, Sydney, Australia; Australian National Liver Transplantation Unit, Royal Prince Alfred Hospital, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
| | - Mark D Gorrell
- Centenary Institute, The University of Sydney, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
| | - Catriona McKenzie
- Faculty of Medicine and Health, The University of Sydney, Sydney, Australia; Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, Australia
| | - James G Kench
- Faculty of Medicine and Health, The University of Sydney, Sydney, Australia; Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, Australia
| | - Ken Liu
- Australian National Liver Transplantation Unit, Royal Prince Alfred Hospital, Sydney, Australia; Centenary Institute, The University of Sydney, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
| | - Geoffrey W McCaughan
- Australian National Liver Transplantation Unit, Royal Prince Alfred Hospital, Sydney, Australia; Centenary Institute, The University of Sydney, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
| | - Michael Crawford
- Centre for Organ Assessment Repair and Optimisation, Royal Prince Alfred Hospital, Sydney, Australia; Australian National Liver Transplantation Unit, Royal Prince Alfred Hospital, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
| | - Carlo Pulitano
- Centre for Organ Assessment Repair and Optimisation, Royal Prince Alfred Hospital, Sydney, Australia; Australian National Liver Transplantation Unit, Royal Prince Alfred Hospital, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
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Kreiner P, Eggenhofer E, Schneider L, Rejas C, Goetz M, Bogovic N, Brunner SM, Evert K, Schlitt HJ, Geissler EK, Junger H. Extrahepatic Bile Duct Organoids as a Model to Study Ischemia/Reperfusion Injury During Liver Transplantation. Transpl Int 2024; 37:13212. [PMID: 39323909 PMCID: PMC11422091 DOI: 10.3389/ti.2024.13212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 08/29/2024] [Indexed: 09/27/2024]
Abstract
Biliary complications are still a major cause for morbidity and mortality after liver transplantation (LT). Ischemia/reperfusion injury (IRI) leads to disruption of the biliary epithelium. We introduce a novel model to study the effect of IRI on human cholangiocytes using extrahepatic cholangiocyte organoids (ECOs). Extrahepatic bile duct tissue was collected during LT at static cold storage and after reperfusion (n = 15); gallbladder tissue was used for controls (n = 5). ECOs (n = 9) were cultured from extrahepatic biliary tissue, with IRI induced in an atmosphere of 95% air (nitrogen), 1% O2 and 5% CO2for 48 h, followed by 24 h of reoxygenation. Qualitative and quantitative histology and qRT-PCR were performed to discern phenotype, markers of hypoxia, programmed cell death and proliferation. ECOs self-organized into circular structures resembling biliary architecture containing cholangiocytes that expressed EpCAM, CK19, LGR5 and SOX-9. After hypoxia, ECOs showed increased expression of VEGF A (p < 0.0001), SLC2A1 (p < 0.0001) and ACSL4 (p < 0.0001) to indicate response to hypoxic damage and subsequent programmed cell death. Increase in cyclin D1 (p < 0.0001) after reoxygenation indicated proliferative activity in ECOs. Therefore, ECO structure and response to IRI are comparable to that found in-vivo, providing a suitable model to study IRI of the bile duct in-vitro.
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Affiliation(s)
- P Kreiner
- Department of Surgery, University Hospital Regensburg, Regensburg, Germany
| | - E Eggenhofer
- Department of Surgery, University Hospital Regensburg, Regensburg, Germany
| | - L Schneider
- Department of Surgery, University Hospital Regensburg, Regensburg, Germany
| | - C Rejas
- Department of Surgery, University Hospital Regensburg, Regensburg, Germany
| | - M Goetz
- Department of Surgery, University Hospital Regensburg, Regensburg, Germany
| | - N Bogovic
- Department of Surgery, University Hospital Regensburg, Regensburg, Germany
| | - S M Brunner
- Department of Surgery, University Hospital Regensburg, Regensburg, Germany
| | - K Evert
- Department of Pathology, University Hospital Regensburg, Regensburg, Germany
| | - H J Schlitt
- Department of Surgery, University Hospital Regensburg, Regensburg, Germany
| | - E K Geissler
- Department of Surgery, University Hospital Regensburg, Regensburg, Germany
| | - H Junger
- Department of Surgery, University Hospital Regensburg, Regensburg, Germany
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Coilly A, Desterke C, Kaščáková S, Chiappini F, Samuel D, Vibert E, Guettier C, Le Naour F. Clinical Application of Infrared Spectroscopy in Liver Transplantation for Rapid Assessment of Lipid Content in Liver Graft. J Transl Med 2024; 104:102110. [PMID: 39004345 DOI: 10.1016/j.labinv.2024.102110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 07/02/2024] [Accepted: 07/08/2024] [Indexed: 07/16/2024] Open
Abstract
Liver transplantation (LT) is a major treatment for patients with end-stage liver diseases. Steatosis is a significant risk factor for primary graft nonfunction and associated with poor long-term graft outcomes. Traditionally, the evaluation of steatosis is based on frozen section examination to estimate the percentage of hepatocytes containing lipid vesicles. However, this visual evaluation correlates poorly with the true lipid content. This study aimed to address the potential of infrared (IR) microspectroscopy for rapidly estimating lipid content in the context of LT and assessing its impact on survival. Clinical data were collected for >20 months from 58 patients who underwent transplantation. For each liver graft, macrovacuolar steatosis and microvesicular steatosis were evaluated through histologic examination of frozen tissue section. Triglycerides (TG) were further quantified using gas phase chromatography coupled with a flame ionization detector (GC-FID) and estimated by IR microspectroscopy. A linear relationship and significant correlation were observed between the TG measured by GC-FID and those estimated using IR microspectroscopy (R2 = 0.86). In some cases, microvesicular steatosis was related to high lipid content despite low levels of macrovacuolar steatosis. Seven patients experienced posttransplantation liver failure, including 5 deceased patients. All patients underwent transplantation with grafts containing significantly high TG levels. A concentration of 250 nmol/mg was identified as the threshold above which the risk of failure after LT significantly increased, affecting 35% of patients. Our study established a strong correlation between LT outcomes and lipid content. IR microspectroscopy proved to be a rapid and reliable approach for assessing the lipid content in clinical settings.
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Affiliation(s)
- Audrey Coilly
- Inserm, Unité 1193, Villejuif, France; Université Paris Saclay, Institut André Lwoff, Villejuif, France; AP-HP Hôpital Paul Brousse, Centre Hépatobiliaire, Villejuif, France
| | - Christophe Desterke
- Université Paris Saclay, Institut André Lwoff, Villejuif, France; Inserm, US33, Villejuif, France
| | - Slávka Kaščáková
- Inserm, Unité 1193, Villejuif, France; Université Paris Saclay, Institut André Lwoff, Villejuif, France
| | - Franck Chiappini
- Inserm, Unité 1193, Villejuif, France; Université Paris Saclay, Institut André Lwoff, Villejuif, France
| | - Didier Samuel
- Inserm, Unité 1193, Villejuif, France; Université Paris Saclay, Institut André Lwoff, Villejuif, France; AP-HP Hôpital Paul Brousse, Centre Hépatobiliaire, Villejuif, France
| | - Eric Vibert
- Inserm, Unité 1193, Villejuif, France; Université Paris Saclay, Institut André Lwoff, Villejuif, France; AP-HP Hôpital Paul Brousse, Centre Hépatobiliaire, Villejuif, France
| | - Catherine Guettier
- Inserm, Unité 1193, Villejuif, France; Université Paris Saclay, Institut André Lwoff, Villejuif, France; AP-HP Hôpital Bicêtre, Service d'Anatomopathologie, Kremlin-Bicêtre, France.
| | - François Le Naour
- Inserm, Unité 1193, Villejuif, France; Université Paris Saclay, Institut André Lwoff, Villejuif, France; Inserm, US33, Villejuif, France.
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Tian X, Wu L, Li X, Zheng W, Zuo H, Song H. Exosomes derived from bone marrow mesenchymal stem cells alleviate biliary ischemia reperfusion injury in fatty liver transplantation by inhibiting ferroptosis. Mol Cell Biochem 2024; 479:881-894. [PMID: 37243945 PMCID: PMC11016128 DOI: 10.1007/s11010-023-04770-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Accepted: 05/15/2023] [Indexed: 05/29/2023]
Abstract
Fatty liver grafts are susceptible to ischemia reperfusion injury (IRI), increasing the risk of biliary complications after liver transplantation (LT). Ferroptosis, a newly recognized programmed cell death, is expected to be a novel therapeutic target for IRI. We investigated whether exosomes derived from heme oxygenase 1-modified bone marrow mesenchymal stem cells (HExos) relieve ferroptosis and protect biliary tracts from IRI in a rat fatty liver transplantation model. Rats were fed with a methionine choline deficient (MCD) diet for 2 weeks to induce severe hepatic steatosis. Steatotic grafts were implanted and HExos were administered after liver transplantation. A series of functional assays and pathological analysis were performed to assess ferroptosis and biliary IRI. The HExos attenuated IRI following liver transplantation, as demonstrated by less ferroptosis, improved liver function, less Kupffer and T cell activation, and less long-term biliary fibrosis. MicroRNA (miR)-204-5p delivered by HExos negatively regulated ferroptosis by targeting a key pro-ferroptosis enzyme, ACSL4. Ferroptosis contributes to biliary IRI in fatty liver transplantation. HExos protect steatotic grafts by inhibiting ferroptosis, and may become a promising strategy to prevent biliary IRI and expand the donor pool.
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Affiliation(s)
- Xuan Tian
- School of Medicine, Nankai University, Tianjin, People's Republic of China
| | - Longlong Wu
- School of Medicine, Nankai University, Tianjin, People's Republic of China
| | - Xiang Li
- Tianjin First Central Hospital Clinic Institute, Tianjin Medical University, Tianjin, 300070, People's Republic of China
| | - Weiping Zheng
- Department of Organ Transplantation, Tianjin First Central Hospital, School of Medicine, Nankai University, No. 24 Fukang Road, Nankai District, Tianjin, 300192, People's Republic of China
- NHC Key Laboratory of Critical Care Medicine, Tianjin, 300192, People's Republic of China
| | - Huaiwen Zuo
- Tianjin First Central Hospital Clinic Institute, Tianjin Medical University, Tianjin, 300070, People's Republic of China
| | - Hongli Song
- Department of Organ Transplantation, Tianjin First Central Hospital, School of Medicine, Nankai University, No. 24 Fukang Road, Nankai District, Tianjin, 300192, People's Republic of China.
- Tianjin Key Laboratory of Organ Transplantation, Tianjin, People's Republic of China.
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Jimenez-Romero C, Justo-Alonso I, del Pozo-Elso P, Marcacuzco-Quinto A, Martín-Arriscado-Arroba C, Manrique-Municio A, Calvo-Pulido J, García-Sesma A, San Román R, Caso-Maestro O. Post-transplant biliary complications using liver grafts from deceased donors older than 70 years: Retrospective case-control study. World J Gastrointest Surg 2023; 15:1615-1628. [PMID: 37701699 PMCID: PMC10494601 DOI: 10.4240/wjgs.v15.i8.1615] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Revised: 03/27/2023] [Accepted: 06/25/2023] [Indexed: 08/25/2023] Open
Abstract
BACKGROUND The shortage of liver grafts and subsequent waitlist mortality led us to expand the donor pool using liver grafts from older donors. AIM To determine the incidence, outcomes, and risk factors for biliary complications (BC) in liver transplantation (LT) using liver grafts from donors aged > 70 years. METHODS Between January 1994 and December 31, 2019, 297 LTs were performed using donors older than 70 years. After excluding 47 LT for several reasons, we divided 250 LTs into two groups, namely post-LT BC (n = 21) and without BC (n = 229). This retrospective case-control study compared both groups. RESULTS Choledocho-choledochostomy without T-tube was the most frequent technique (76.2% in the BC group vs 92.6% in the non-BC group). Twenty-one patients (8.4%) developed BC (13 anastomotic strictures, 7 biliary leakages, and 1 non-anastomotic biliary stricture). Nine patients underwent percutaneous balloon dilation and nine required a Roux-en-Y hepaticojejunostomy because of dilation failure. The incidence of post-LT complications (graft dysfunction, rejection, renal failure, and non-BC reoperations) was similar in both groups. There were no significant differences in the patient and graft survival between the groups. Moreover, only three deaths were attributed to BC. While female donors were protective factors for BC, donor cardiac arrest was a risk factor. CONCLUSION The incidence of BC was relatively low on using liver grafts > 70 years. It could be managed in most cases by percutaneous dilation or Roux-en-Y hepaticojejunostomy, without significant differences in the patient or graft survival between the groups.
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Affiliation(s)
- Carlos Jimenez-Romero
- Unit of HPB Surgery and Abdominal Organs Transplantation, `12 de Octubre´ University Hospital, Madrid 28041, Spain
| | - Iago Justo-Alonso
- Unit of HPB Surgery and Abdominal Organs Transplantation, `12 de Octubre´ University Hospital, Madrid 28041, Spain
| | - Pilar del Pozo-Elso
- Unit of HPB Surgery and Abdominal Organs Transplantation, `12 de Octubre´ University Hospital, Madrid 28041, Spain
| | - Alberto Marcacuzco-Quinto
- Unit of HPB Surgery and Abdominal Organs Transplantation, `12 de Octubre´ University Hospital, Madrid 28041, Spain
| | | | - Alejandro Manrique-Municio
- Unit of HPB Surgery and Abdominal Organs Transplantation, `12 de Octubre´ University Hospital, Madrid 28041, Spain
| | - Jorge Calvo-Pulido
- Unit of HPB Surgery and Abdominal Organs Transplantation, `12 de Octubre´ University Hospital, Madrid 28041, Spain
| | - Alvaro García-Sesma
- Unit of HPB Surgery and Abdominal Organs Transplantation, `12 de Octubre´ University Hospital, Madrid 28041, Spain
| | - Ricardo San Román
- Department of Radiology, `12 de Octubre´ University Hospital, Madrid 28041, Spain
| | - Oscar Caso-Maestro
- Unit of HPB Surgery and Abdominal Organs Transplantation, `12 de Octubre´ University Hospital, Madrid 28041, Spain
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Tingle SJ, Thompson ER, Bates L, Ibrahim IK, Govaere O, Shuttleworth V, Wang L, Figueiredo R, Palmer J, Bury Y, Anstee QM, Wilson C. Pharmacological testing of therapeutics using normothermic machine perfusion: A pilot study of 2,4-dinitrophenol delivery to steatotic human livers. Artif Organs 2022; 46:2201-2214. [PMID: 35546070 DOI: 10.1111/aor.14309] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 04/19/2022] [Accepted: 04/29/2022] [Indexed: 12/01/2022]
Abstract
INTRODUCTION Normothermic machine perfusion (NMP) provides a platform for drug-delivery. However, pharmacological considerations for therapeutics delivered during NMP are scarcely reported. We aimed to demonstrate the ability of NMP as a platform for pharmacological testing, using a drug which increases metabolism (2,4-dinitrophenol; DNP) as an example therapeutic. METHODS We performed 25 h of NMP on human livers which had been declined for transplant due to steatosis (n = 7). Three livers received a DNP bolus, three were controls, and one received a DNP infusion. RESULTS Toxicity studies revealed DNP delivery was safe, without hepatotoxic effects. The liver surface temperature was increased in the DNP group (p = 0.046), but no livers suffered hyperthermia-the mechanism of DNP toxicity in vivo. Pharmacokinetic studies revealed DNP elimination with first-order kinetics and 7.7 h half-life (95% CI = 5.1-15.9 hrs). The clearance of DNP in bile was negligible. As expected, DNP significantly increased oxygen consumption (p = 0.023); this increase was closely correlated with perfusate DNP concentration (r2 = 0.975; p = 0.002) and the effect was lost as DNP was eliminated by the liver. A DNP infusion rate, calculated using our pharmacokinetic data, successfully maintained perfusate DNP concentration. DISCUSSION Detailed pharmacological testing can be performed during NMP. Our therapeutic (DNP) is rapidly eliminated by the ex vivo liver, meaning the drug effect of increased metabolism is only transient. This demonstrates the importance of assessing pharmacokinetics when delivering therapeutics during NMP, especially for prolonged perfusion of organs with established roles in drug elimination. Rigorous pharmacological testing is needed to unlock the potential of NMP as a clinical drug-delivery platform.
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Affiliation(s)
- Samuel J Tingle
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
- Department of HPB and Transplant Surgery, Freeman Hospital, Newcastle upon Tyne, UK
- Blood and Transplant Research Unit, Newcastle University, Newcastle upon Tyne, UK
| | - Emily R Thompson
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
- Department of HPB and Transplant Surgery, Freeman Hospital, Newcastle upon Tyne, UK
- Blood and Transplant Research Unit, Newcastle University, Newcastle upon Tyne, UK
| | - Lucy Bates
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
- Blood and Transplant Research Unit, Newcastle University, Newcastle upon Tyne, UK
| | - Ibrahim K Ibrahim
- Department of HPB and Transplant Surgery, Freeman Hospital, Newcastle upon Tyne, UK
| | - Olivier Govaere
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
| | - Victoria Shuttleworth
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
| | - Lu Wang
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
- Blood and Transplant Research Unit, Newcastle University, Newcastle upon Tyne, UK
| | - Rodrigo Figueiredo
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
- Department of HPB and Transplant Surgery, Freeman Hospital, Newcastle upon Tyne, UK
| | - Jeremy Palmer
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
| | - Yvonne Bury
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
- Department of Cellular Pathology, Victoria Infirmary, Newcastle upon Tyne, UK
| | - Quentin M Anstee
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
- Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Colin Wilson
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
- Department of HPB and Transplant Surgery, Freeman Hospital, Newcastle upon Tyne, UK
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Widmer J, Eden J, Carvalho MF, Dutkowski P, Schlegel A. Machine Perfusion for Extended Criteria Donor Livers: What Challenges Remain? J Clin Med 2022; 11:jcm11175218. [PMID: 36079148 PMCID: PMC9457017 DOI: 10.3390/jcm11175218] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 08/30/2022] [Indexed: 11/28/2022] Open
Abstract
Based on the renaissance of dynamic preservation techniques, extended criteria donor (ECD) livers reclaimed a valuable eligibility in the transplantable organ pool. Being more vulnerable to ischemia, ECD livers carry an increased risk of early allograft dysfunction, primary non-function and biliary complications and, hence, unveiled the limitations of static cold storage (SCS). There is growing evidence that dynamic preservation techniques—dissimilar to SCS—mitigate reperfusion injury by reconditioning organs prior transplantation and therefore represent a useful platform to assess viability. Yet, a debate is ongoing about the advantages and disadvantages of different perfusion strategies and their best possible applications for specific categories of marginal livers, including organs from donors after circulatory death (DCD) and brain death (DBD) with extended criteria, split livers and steatotic grafts. This review critically discusses the current clinical spectrum of livers from ECD donors together with the various challenges and posttransplant outcomes in the context of standard cold storage preservation. Based on this, the potential role of machine perfusion techniques is highlighted next. Finally, future perspectives focusing on how to achieve higher utilization rates of the available donor pool are highlighted.
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Affiliation(s)
- Jeannette Widmer
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, 8091 Zürich, Switzerland
| | - Janina Eden
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, 8091 Zürich, Switzerland
| | - Mauricio Flores Carvalho
- Hepatobiliary Unit, Department of Clinical and Experimental Medicine, University of Florence, AOU Careggi, 50139 Florence, Italy
| | - Philipp Dutkowski
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, 8091 Zürich, Switzerland
| | - Andrea Schlegel
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, 8091 Zürich, Switzerland
- Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Centre of Preclinical Research, 20122 Milan, Italy
- Correspondence:
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8
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Schlegel A, Foley DP, Savier E, Flores Carvalho M, De Carlis L, Heaton N, Taner CB. Recommendations for Donor and Recipient Selection and Risk Prediction: Working Group Report From the ILTS Consensus Conference in DCD Liver Transplantation. Transplantation 2021; 105:1892-1903. [PMID: 34416750 DOI: 10.1097/tp.0000000000003825] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Although the utilization of donation after circulatory death donors (DCDs) for liver transplantation (LT) has increased steadily, much controversy remains, and no common acceptance criteria exist with regard to donor and recipient risk factors and prediction models. A consensus conference was organized by International Liver Transplantation Society on January 31, 2020, in Venice, Italy, to review the current clinical practice worldwide regarding DCD-LT and to develop internationally accepted guidelines. The format of the conference was based on the grade system. International experts in this field were allocated to 6 working groups and prepared evidence-based recommendations to answer-specific questions considering the currently available literature. Working group members 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 recommendations provided by working group 2, covering the entire spectrum of donor and recipient risk factors and prediction models in DCD-LT.
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Affiliation(s)
- Andrea Schlegel
- The Liver Unit, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham, United Kingdom
- Hepatobiliary Unit, Department of Clinical and Experimental Medicine, University of Florence, AOU Careggi, Florence, Italy
| | - David P Foley
- University of Wisconsin School of Medicine and Public Health, William S. Middleton VA Medical Center, Madison, WI
| | - Eric Savier
- Department of Hepatobiliary Surgery and Liver Transplantation, Sorbonne Université Pitié-Salpêtrière Hospital, Paris, France
| | - Mauricio Flores Carvalho
- Hepatobiliary Unit, Department of Clinical and Experimental Medicine, University of Florence, AOU Careggi, Florence, Italy
| | - Luciano De Carlis
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
- School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
| | - Nigel Heaton
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - C Burcin Taner
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
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9
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Magro B, Tacelli M, Mazzola A, Conti F, Celsa C. Biliary complications after liver transplantation: current perspectives and future strategies. Hepatobiliary Surg Nutr 2021; 10:76-92. [PMID: 33575291 DOI: 10.21037/hbsn.2019.09.01] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2019] [Accepted: 08/29/2019] [Indexed: 12/29/2022]
Abstract
Importance Liver transplantation (LT) is a life-saving therapy for patients with end-stage liver disease and with acute liver failure, and it is associated with excellent outcomes and survival rates at 1 and 5 years. The incidence of biliary complications (BCs) after LT is reported to range from 5% to 20%, most of them occurring in the first three months, although they can occur also several years after transplantation. Objective The aim of this review is to summarize the available evidences on pathophysiology, risk factors, diagnosis and therapeutic management of BCs after LT. Evidence Review a literature review was performed of papers on this topic focusing on risk factors, classifications, diagnosis and treatment. Findings Principal risk factors include surgical techniques and donor's characteristics for biliary leakage and anastomotic biliary strictures and vascular alterations for non- anastomotic biliary strictures. MRCP is the gold standard both for intra- and extrahepatic BCs, while invasive cholangiography should be restricted for therapeutic uses or when MRCP is equivocal. About treatment, endoscopic techniques are the first line of treatment with success rates of 70-100%. The combined success rate of ERCP and PTBD overcome 90% of cases. Biliary leaks often resolve spontaneously, or with the positioning of a stent in ERCP for major bile leaks. Conclusions and Relevance BCs influence morbidity and mortality after LT, therefore further evidences are needed to identify novel possible risk factors, to understand if an immunological status that could lead to their development exists and to compare the effectiveness of innovative surgical and machine perfusion techniques.
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Affiliation(s)
- Bianca Magro
- Section of Gastroenterology and Hepatology, Dipartimento di Promozione della Salute, Materno-Infantile, Medicina Interna e Specialistica di Eccellenza (PROMISE), University of Palermo, Palermo, Italy.,Service d'Hépatologie et Transplantation Hépatique, Hôpital de la Pitié Salpétrière, AP-HP, Paris, France
| | - Matteo Tacelli
- Section of Gastroenterology and Hepatology, Dipartimento di Promozione della Salute, Materno-Infantile, Medicina Interna e Specialistica di Eccellenza (PROMISE), University of Palermo, Palermo, Italy
| | - Alessandra Mazzola
- Service d'Hépatologie et Transplantation Hépatique, Hôpital de la Pitié Salpétrière, AP-HP, Paris, France
| | - Filomena Conti
- Service d'Hépatologie et Transplantation Hépatique, Hôpital de la Pitié Salpétrière, AP-HP, Paris, France
| | - Ciro Celsa
- Section of Gastroenterology and Hepatology, Dipartimento di Promozione della Salute, Materno-Infantile, Medicina Interna e Specialistica di Eccellenza (PROMISE), University of Palermo, Palermo, Italy
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10
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Dumortier J, Chambon-Augoyard C, Guillaud O, Pioche M, Rivory J, Valette PJ, Adham M, Ponchon T, Scoazec JY, Boillot O. Anastomotic bilio-biliary stricture after adult liver transplantation: A retrospective study over 20 years in a single center. Clin Res Hepatol Gastroenterol 2020; 44:564-571. [PMID: 31547998 DOI: 10.1016/j.clinre.2019.08.008] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Revised: 08/20/2019] [Accepted: 08/23/2019] [Indexed: 02/08/2023]
Abstract
BACKGROUND Biliary complications are the main surgical complication after liver transplantation (LT). The aims of the present retrospective single center study were to describe anastomotic bilio-biliary strictures (ABS) in a large cohort of liver transplant recipients with long follow-up. METHODS All adult LT recipients who underwent a LT, with bilio-biliary anastomosis, between 1990 and 2010 in Edouard Herriot hospital, Lyon, France were included in the study. RESULTS The study population consisted in 783 patients (70.0% males), median age 50.5 years; main indication was alcohol-related liver disease (46.8%). The median follow-up after LT was 11.9 years (range 0-27 years). The overall incidence of anastomotic biliary complications was 9.7%: 50 patients developed an ABS (6.6%), after a median delay of 4.4 months (range 0.1-245.2) after LT and 32 (4.1%) developed biliary leakage after a median delay of 25 days (range 1-179). The actuarial risk of developing an ABS was 1.6% at 1-month, 2.7% at 3-months, 4.1% at 6-months, and 5.1%, 6.0%, 6.4%, 6.6%, 7.3% at 1-, 2-, 5-, 10- and 15-years, respectively. Univariate analysis disclosed that post-reperfusion syndrome and liver graft steatosis (≥30%) were significant risk factors for ABS. Multivariate analysis disclosed that graft steatosis (OR=6.262, 95%CI 1.936-20.257, P=0.002) and MELD score (OR=1.071, 95%CI 1.018-1.128, P=0.008) were significant risk factors for ABS. The first-line treatment of ABS consisted in endoscopic stenting for 44 patients (88.0%) and immediate success rate was 75.0%. Delayed recurrence of ABS occurred in 8/33 patients (24.0%). CONCLUSION Our results suggest that steatotic grafts should be used for recipients without severe liver failure to avoid ABS, and that endoscopic stenting of post-LT ABS leads to a high success rate, but is associated with a significant risk of recurrence.
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Affiliation(s)
- Jérôme Dumortier
- Hospices Civils de Lyon, Hôpital Edouard Herriot, Unité de Transplantation hépatique, Lyon, France; Hospices Civils de Lyon, Hôpital Edouard Herriot, Service d'Hépato-gastroentérologie, Lyon, France; Université Claude Bernard Lyon 1, Lyon, France.
| | - Christine Chambon-Augoyard
- Hospices Civils de Lyon, Hôpital Edouard Herriot, Unité de Transplantation hépatique, Lyon, France; Hospices Civils de Lyon, Hôpital Edouard Herriot, Service d'Hépato-gastroentérologie, Lyon, France
| | - Olivier Guillaud
- Hospices Civils de Lyon, Hôpital Edouard Herriot, Unité de Transplantation hépatique, Lyon, France; Hospices Civils de Lyon, Hôpital Edouard Herriot, Service d'Hépato-gastroentérologie, Lyon, France
| | - Mathieu Pioche
- Hospices Civils de Lyon, Hôpital Edouard Herriot, Service d'Hépato-gastroentérologie, Lyon, France
| | - Jérôme Rivory
- Hospices Civils de Lyon, Hôpital Edouard Herriot, Service d'Hépato-gastroentérologie, Lyon, France
| | - Pierre-Jean Valette
- Université Claude Bernard Lyon 1, Lyon, France; Hospices Civils de Lyon, Hôpital Edouard Herriot, Service de Radiologie digestive, Lyon, France
| | - Mustapha Adham
- Hospices Civils de Lyon, Hôpital Edouard Herriot, Unité de Transplantation hépatique, Lyon, France; Université Claude Bernard Lyon 1, Lyon, France
| | - Thierry Ponchon
- Hospices Civils de Lyon, Hôpital Edouard Herriot, Service d'Hépato-gastroentérologie, Lyon, France; Université Claude Bernard Lyon 1, Lyon, France
| | - Jean-Yves Scoazec
- Université Claude Bernard Lyon 1, Lyon, France; Hospices Civils de Lyon, Hôpital Edouard Herriot, Service d'Anatomie et Cytologie Pathologiques, Lyon, France
| | - Olivier Boillot
- Hospices Civils de Lyon, Hôpital Edouard Herriot, Unité de Transplantation hépatique, Lyon, France; Université Claude Bernard Lyon 1, Lyon, France
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11
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Liu WY, Li XX, Fu XY, Wu XD, Wang X, Guo Y, Zang YJ, Wang JH. Combination of liver graft sonographic grading and point shear wave elastography to reduce early allograft dysfunction after liver transplantation. Eur Radiol 2020; 30:5191-5199. [PMID: 32328762 DOI: 10.1007/s00330-020-06842-5] [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: 12/31/2019] [Revised: 03/03/2020] [Accepted: 03/30/2020] [Indexed: 11/24/2022]
Abstract
OBJECTIVE To analyze the performance of a liver graft sonographic grading system and point shear wave elastography (PSWE) in predicting early allograft dysfunction (EAD) after liver transplantation (LT). METHODS Successive brain-dead donors and liver recipients in our hospital from March 2017 to May 2018 were retrospectively recruited. All donors underwent PSWE examination, abdominal ultrasonography, and sonographic grading (grade 0 to grade 5). Donors with ≥ 10 valid PSWE examinations and a failure rate of < 60% were included. For all recipients, abdominal ultrasonography and blood tests for biologic parameters were performed preoperatively and daily postoperatively to screen for EAD. The recipients and their grafts were classified into EAD and non-EAD groups. Statistical analyses were performed to analyze the correlations among liver stiffness (LS), liver graft sonographic grading, and EAD. RESULTS Thirty-two donors and 32 corresponding liver recipients were enrolled (15 cases in the EAD group; 17 in the non-EAD group). There were no grade 0, 1, or 2 cases in the two groups. For prediction of EAD in recipients after LT, the AUC for PSWE was 0.929 and the AUC for combination of PSWE and sonographic grading system was 0.935. CONCLUSIONS Combination of PSWE and sonographic grading system can predict postoperative EAD in LT recipients with high sensitivity. Abnormal results may suggest a need for liver biopsy preoperatively, thus avoiding unnecessary surgical preparation for liver procurement. KEY POINTS • Combination of PSWE with new sonographic grading system is useful for preoperative evaluation of liver grafts from brain-dead donors. • EAD is as a criterion for evaluating the diagnostic value of PSWE and sonographic grading system. • Combination of PSWE and sonographic grading system can predict postoperative EAD in LT recipients with high sensitivity.
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Affiliation(s)
- Wen-Yi Liu
- Organ Transplantation Department, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Southern Distinct, Qingdao, 266003, Shandong, China
| | - Xuan-Xuan Li
- Ultrasound Department, Qingdao Haici Hospital, No. 4, Renmin Road, Qingdao, 266003, Shandong, China
| | - Xiao-Yue Fu
- Organ Transplantation Department, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Southern Distinct, Qingdao, 266003, Shandong, China
| | - Xiao-Dong Wu
- Organ Transplantation Department, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Southern Distinct, Qingdao, 266003, Shandong, China
| | - Xin Wang
- Organ Transplantation Department, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Southern Distinct, Qingdao, 266003, Shandong, China
| | - Yuan Guo
- Organ Transplantation Department, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Southern Distinct, Qingdao, 266003, Shandong, China
| | - Yun-Jin Zang
- Organ Transplantation Department, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Southern Distinct, Qingdao, 266003, Shandong, China.
| | - Jian-Hong Wang
- Organ Transplantation Department, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Southern Distinct, Qingdao, 266003, Shandong, China.
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12
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Transient elastography for assessment of fibrosis and steatosis of liver grafts from brain-death donors. Clin Res Hepatol Gastroenterol 2020; 44:155-161. [PMID: 31992509 DOI: 10.1016/j.clinre.2019.06.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Revised: 05/25/2019] [Accepted: 06/07/2019] [Indexed: 02/04/2023]
Abstract
BACKGROUND An objective and accurate evaluation of liver grafts is required to improve the prognosis of liver transplant recipients and to increase the number of available liver grafts. AIM To compare outcomes using FibroScan with that of pathology in liver grafts from brain-dead donors (DBD). METHODS Liver grafts from 52 DBD were examined using ultrasound (US), FibroScan before liver transplantation (LT). Blood tested before LT and a biopsy was performed pre- or intra-operation to determine pathology. The diagnostic accuracy of the FibroScan results was compared with the pathology results, which is the gold standard for evaluating liver grafts. The donors enrolled were grouped by the stage of liver fibrosis (F0-F4) and steatosis (S0-S3), based on Kleiner's scoring system of nonalcoholic fatty liver disease, respectively. RESULTS The liver stiffness (LS) value in group F1 was significantly increased compared with group F0 (8.74±1.32kPa and 5.93±1.64kPa, respectively, P<0.01). The LS value had a significant positive correlation with the liver graft fibrosis stage (r=0.73, P<0.01). The area under receiver operating characteristic curves (AUROC) for F1 stage fibrosis was 0.93 (P<0.01). Significant differences in the controlled attenuation parameter (CAP) were found among groups S0, S1, and S2 (173.30±38.36dB/m, 230.29±23.27dB/m, 250.00±57.01dB/m, respectively; F=12.41, P<0.01). The CAP was associated with the liver graft steatosis stage (r=0.64, P<0.01). The AUROC for S1 and S2 stage steatosis in liver grafts was 0.89 (P=0.002) and 0.83 (P=0.007), respectively. CONCLUSIONS Transient elastography quantifies fibrosis and steatosis in liver grafts from 52 DBD with a high diagnostic accuracy and provides further imaging evidence for use in assessing liver grafts.
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13
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Kaldas FM, Korayem IM, Russell TA, Agopian VG, Aziz A, DiNorcia J, Farmer DG, Yersiz H, Hiatt JR, Busuttil RW. Assessment of Anastomotic Biliary Complications in Adult Patients Undergoing High-Acuity Liver Transplant. JAMA Surg 2020; 154:431-439. [PMID: 30758485 DOI: 10.1001/jamasurg.2018.5527] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Importance Anastomotic biliary complications (ABCs) constitute the most common technical complications in liver transplant (LT). Given the ever-increasing acuity of LT, identification of factors contributing to ABCs is essential to minimize morbidity and optimize outcomes. A detailed analysis in a patient population undergoing high-acuity LT is lacking. Objective To evaluate the rate of, risk factors for, and outcomes of ABCs and acuity level in LT recipients. Design, Setting, and Participants This retrospective cohort study included adult LT recipients from January 1, 2013, through June 30, 2016, at a single large urban transplant center. Patients were followed up for at least 12 months after LT until June 30, 2017. Of 520 consecutive adult patients undergoing LT, 509 LTs in 503 patients were included. Data were analyzed from May 1 through September 13, 2017. Exposure Liver transplant. Main Outcomes and Measures Any complications occurring at the level of the biliary reconstruction. Results Among the 503 transplant recipients undergoing 509 LTs included in the analysis (62.3% male; median age, 58 years [interquartile range {IQR}, 50-63 years), median follow-up was 24 months (IQR, 16-34 months). Overall patient and graft survival at 1 year were 91.1% and 90.3%, respectively. The median Model for End-stage Liver Disease (MELD) score was 35 (IQR, 15-40) for the entire cohort. T tubes were used in 199 LTs (39.1%) during initial bile duct reconstruction. Overall incidence of ABCs included 103 LTs (20.2%). Anastomotic leak occurred in 25 LTs (4.9%) and stricture, 77 (15.1%). Exit-site leak in T tubes occurred in 36 (7.1%) and T tube obstruction in 16 (3.1%). Seventeen patients with ABCs required surgical revision of bile duct reconstruction. Multivariate analysis revealed the following 7 independent risk factors for ABCs: recipient hepatic artery thrombosis (odds ratio [OR], 12.41; 95% CI, 2.37-64.87; P = .003), second LT (OR, 4.05; 95% CI, 1.13-14.50; P = .03), recipient hepatic artery stenosis (OR, 3.81; 95% CI, 1.30-11.17; P = .02), donor hypertension (OR, 2.79; 95% CI, 1.27-6.11; P = .01), recipients with hepatocellular carcinoma (OR, 2.66; 95% CI, 1.23-5.74; P = .01), donor death due to anoxia (OR, 2.61; 95% CI, 1.13-6.03; P = .03), and use of nonabsorbable suture material for biliary reconstruction (OR, 2.45; 95% CI, 1.09-5.54; P = .03). Conclusions and Relevance This large, single-center series identified physiologic and anatomical independent risk factors contributing to ABCs after high-acuity LT. Careful consideration of these factors could guide perioperative management and mitigate potentially preventable ABCs.
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Affiliation(s)
- Fady M Kaldas
- Dumont-UCLA (University of California, Los Angeles) Transplant and Liver Cancer Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine, UCLA
| | - Islam M Korayem
- Dumont-UCLA (University of California, Los Angeles) Transplant and Liver Cancer Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine, UCLA.,Hepato-Pancreato-Biliary Surgery Unit, Department of Surgery, Faculty of Medicine, University of Alexandria, Alexandria, Egypt
| | - Tara A Russell
- Dumont-UCLA (University of California, Los Angeles) Transplant and Liver Cancer Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine, UCLA
| | - Vatche G Agopian
- Dumont-UCLA (University of California, Los Angeles) Transplant and Liver Cancer Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine, UCLA
| | - Antony Aziz
- Dumont-UCLA (University of California, Los Angeles) Transplant and Liver Cancer Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine, UCLA
| | - Joseph DiNorcia
- Dumont-UCLA (University of California, Los Angeles) Transplant and Liver Cancer Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine, UCLA
| | - Douglas G Farmer
- Dumont-UCLA (University of California, Los Angeles) Transplant and Liver Cancer Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine, UCLA
| | - Hasan Yersiz
- Dumont-UCLA (University of California, Los Angeles) Transplant and Liver Cancer Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine, UCLA
| | - Jonathan R Hiatt
- Dumont-UCLA (University of California, Los Angeles) Transplant and Liver Cancer Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine, UCLA
| | - Ronald W Busuttil
- Dumont-UCLA (University of California, Los Angeles) Transplant and Liver Cancer Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine, UCLA
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14
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Inflammasome-Mediated Inflammation in Liver Ischemia-Reperfusion Injury. Cells 2019; 8:cells8101131. [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] [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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15
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Crismale JF, Ahmad J. Endoscopic Management of Biliary Issues in the Liver Transplant Patient. Gastrointest Endosc Clin N Am 2019; 29:237-256. [PMID: 30846151 DOI: 10.1016/j.giec.2018.11.003] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Biliary complications remain a common problem after liver transplantation (LT). The therapeutic endoscopist encounters a variety of situations in LT including strictures at the duct-to-duct biliary anastomosis, strictures elsewhere in the biliary tree caused by an ischemic injury, and bile leaks at the anastomosis or from the cut surface and stone disease. Biliary complications lead to significant morbidity and occasionally reduced graft and patient survival. Several factors increase the risk of strictures and leaks. Endoscopic intervention in experienced hands is successful in the management of biliary complications following LT and percutaneous or surgical correction should seldom be required.
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Affiliation(s)
- James F Crismale
- Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA
| | - Jawad Ahmad
- Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
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16
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Golse N, Cosse C, Allard MA, Laurenzi A, Tedeschi M, Guglielmo N, Fernandez-Sevilla E, Robert M, Tréchot B, Pietrasz D, Pittau G, Ciacio O, Sa Cunha A, Castaing D, Cherqui D, Adam R, Samuel D, Sebagh M, Vibert E. Evaluation of a micro-spectrometer for the real-time assessment of liver graft with mild-to-moderate macrosteatosis: A proof of concept study. J Hepatol 2019; 70:423-430. [PMID: 30399385 DOI: 10.1016/j.jhep.2018.10.034] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Revised: 10/24/2018] [Accepted: 10/27/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS Liver macrosteatosis (MS) is a major predictor of graft dysfunction after transplantation. However, frozen section techniques to quantify steatosis are often unavailable in the context of procurements, and the findings of preoperative imaging techniques correlate poorly with those of permanent sections, so that the surgeon is ultimately responsible for the decision. Our aim was to assess the accuracy of a non-invasive pocket-sized micro-spectrometer (PSM) for the real-time estimation of MS. METHODS We prospectively evaluated a commercial PSM by scanning the liver capsule. A double pathological quantification of MS was performed on permanent sections. Initial calibration (training cohort) was performed on 35 livers (MS ≤60%) and an algorithm was created to correlate the estimated (PSM) and known (pathological) MS values. A second assessment (validation cohort) was then performed on 154 grafts. RESULTS Our algorithm achieved a coefficient of determination R2 = 0.81. Its validation on the second cohort demonstrated a Lin's concordance coefficient of 0.78. Accuracy reached 0.91%, with reproducibility of 86.3%. The sensitivity, specificity, positive and negative predictive values for MS ≥30% were 66.7%, 100%, 100% and 98%, respectively. The PSM could predict the absence (<30%)/presence (≥30%) of MS with a kappa coefficient of 0.79. Neither graft weight nor height, donor body mass index nor the CT-scan liver-to-spleen attenuation ratio could accurately predict MS. CONCLUSION We demonstrated that a PSM can reliably and reproducibly assess mild-to-moderate MS. Its low cost and the immediacy of results may offer considerable added-value decision support for surgeons. This tool could avoid the detrimental and prolonged ischaemia caused by the pathological examination of (potentially) marginal grafts. This device now needs to be assessed in the context of a large-scale multicentre study. LAY SUMMARY Macro-vacuolar liver steatosis is a major prognostic factor for outcomes after liver transplantation. However, it is often difficult for logistical reasons to get this estimation during procurement. Therefore, we developed an algorithm for a commercial, portable and affordable spectrometer to accurately estimate this content in a real-time fashion. This device could be of great interest for clinical decision-making to accept or discard a potential human liver graft.
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Affiliation(s)
- Nicolas Golse
- Department of Surgery, Paul-Brousse Hospital Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif 94800, France; DHU Hepatinov, Villejuif 94800, France; INSERM, Unit 1193, Villejuif 94800, France; Univ Paris-Sud, UMR-S 1193, Villejuif 94800, France.
| | - Cyril Cosse
- Faculty of Medicine Paris V, Paris 75020, France
| | - Marc-Antoine Allard
- Department of Surgery, Paul-Brousse Hospital Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif 94800, France
| | - Andrea Laurenzi
- Department of Surgery, Paul-Brousse Hospital Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif 94800, France
| | - Michele Tedeschi
- Department of Surgery, Paul-Brousse Hospital Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif 94800, France
| | - Nicola Guglielmo
- Department of Surgery, Paul-Brousse Hospital Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif 94800, France
| | - Elena Fernandez-Sevilla
- Department of Surgery, Paul-Brousse Hospital Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif 94800, France
| | - Maud Robert
- Department of General Surgery and Bariatric Surgery, Edouard Herriot Hospital, Hospices Civils de Lyon-Claude Bernard Lyon 1 University, France
| | - Boris Tréchot
- Department of Surgery, Paul-Brousse Hospital Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif 94800, France
| | - Daniel Pietrasz
- Department of Surgery, Paul-Brousse Hospital Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif 94800, France
| | - Gabriella Pittau
- Department of Surgery, Paul-Brousse Hospital Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif 94800, France
| | - Oriana Ciacio
- Department of Surgery, Paul-Brousse Hospital Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif 94800, France
| | - Antonio Sa Cunha
- Department of Surgery, Paul-Brousse Hospital Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif 94800, France; DHU Hepatinov, Villejuif 94800, France; INSERM, Unit 1193, Villejuif 94800, France; Univ Paris-Sud, UMR-S 1193, Villejuif 94800, France
| | - Denis Castaing
- Department of Surgery, Paul-Brousse Hospital Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif 94800, France; DHU Hepatinov, Villejuif 94800, France; INSERM, Unit 1193, Villejuif 94800, France; Univ Paris-Sud, UMR-S 1193, Villejuif 94800, France
| | - Daniel Cherqui
- Department of Surgery, Paul-Brousse Hospital Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif 94800, France; DHU Hepatinov, Villejuif 94800, France; INSERM, Unit 1193, Villejuif 94800, France; Univ Paris-Sud, UMR-S 1193, Villejuif 94800, France
| | - René Adam
- Department of Surgery, Paul-Brousse Hospital Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif 94800, France; DHU Hepatinov, Villejuif 94800, France; INSERM, Unit 776, Villejuif F-94800, France; Univ Paris-Sud, UMR-S 776, Villejuif 94800, France
| | - Didier Samuel
- DHU Hepatinov, Villejuif 94800, France; INSERM, Unit 1193, Villejuif 94800, France; Univ Paris-Sud, UMR-S 1193, Villejuif 94800, France; Department of Hepatology, Paul-Brousse Hospital Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif 94800, France
| | - Mylene Sebagh
- Department of Pathology, Paul-Brousse Hospital Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif 94800, France
| | - Eric Vibert
- Department of Surgery, Paul-Brousse Hospital Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif 94800, France; DHU Hepatinov, Villejuif 94800, France; INSERM, Unit 1193, Villejuif 94800, France; Univ Paris-Sud, UMR-S 1193, Villejuif 94800, France
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17
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Lattanzi B, Ott P, Rasmussen A, Kudsk KR, Merli M, Villadsen GE. Ischemic Damage Represents the Main Risk Factor for Biliary Stricture After Liver Transplantation: A Follow-Up Study in a Danish Population. In Vivo 2019; 32:1623-1628. [PMID: 30348725 DOI: 10.21873/invivo.11423] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2018] [Revised: 08/03/2018] [Accepted: 08/06/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND Biliary complications (BC) are frequently observed following liver transplantation. The aim of the present retrospective study, conducted at an outpatients' tertiary care hospital, was to determine the incidence of biliary complications and risk factors associated with their development in liver transplantation (lT) patients. MATERIALS AND METHODS The medical records were reviewed for all patients who underwent liver transplantation at the Rigshospitalet, Copenhagen, Denmark, from 2000 to 2011 and were referred to the Aarhus University Hospital for follow-up. Patients who died within 3 months of surgery or had incomplete clinical information were excluded. All data for demographic characteristics and possible risk factors for development of biliary stricture were collected. Fifty-one patients were included. RESULTS The median age at transplantation was 40 (range=7-64) years, and 53% of patients were males. Biliary complications occurred in 18 patients (35%), the majority of whom developed strictures (12 patients, 24%). Univariate and multivariate analyses revealed that cytomegalovirus infection (p=0.008), hepatic artery obstruction (p=0.03) and hepatic artery graft abnormalities (p=0.03) were independent risk factors for the development of biliary strictures. CONCLUSION One-third of patients presented biliary complications after liver transplantation, among which biliary strictures were the most common. Cytomegalovirus infection, hepatic artery stenosis and anatomical abnormality of the graft's hepatic artery are independent risk factors for the development of biliary stricture.
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Affiliation(s)
- Barbara Lattanzi
- Department of Clinical Medicine, Umberto 1 Hospital, Rome, Italy
| | - Peter Ott
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Allan Rasmussen
- Department of Surgical Gastroenterology and Liver Transplantation, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Karen Raben Kudsk
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Manuela Merli
- Department of Clinical Medicine, Umberto 1 Hospital, Rome, Italy
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18
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Trapero-Marugán M, Little EC, Berenguer M. Stretching the boundaries for liver transplant in the 21st century. Lancet Gastroenterol Hepatol 2018; 3:803-811. [DOI: 10.1016/s2468-1253(18)30213-9] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Revised: 06/20/2018] [Accepted: 06/22/2018] [Indexed: 12/12/2022]
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19
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Ciria R, Navarro E, Sánchez-Frías M, Gallardo AB, Medina J, Ayllón MD, Gomez-Luque I, Ruiz-Rabelo J, Luque A, de la Mata M, Rufián S, López-Cillero P, Briceño J. Preliminary results from the use of intraoperative real-time biliary oxygen monitoring in liver transplantation. Clin Transplant 2018; 32:e13433. [PMID: 30365182 DOI: 10.1111/ctr.13433] [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: 05/17/2018] [Revised: 10/16/2018] [Accepted: 10/19/2018] [Indexed: 11/27/2022]
Abstract
BACKGROUND AND AIMS Biliary anastomosis is a frequent area of complications after liver transplantation (LT) and a potential area of "microangiopathy". The concept of a "marginal bile duct" is unexplored. The main aim was to make a preliminary evaluation of the utility of an innovative real-time oxygen microtension (pO2mt) testing device for the assessment of bile duct viability during LT and to correlate these pO2mt values with microvascular tissue quality by histopathology and outcomes. PATIENTS AND METHODS Observational prospective cohort study with 23 patients. Oxygen microtension measurements were made placing a micropO2 probe in different areas of recipient and donor's bile duct intraoperative. RESULTS Mean pO2mt in the graft bile duct at the level of the anastomosis 103.82 (31-157) mm Hg, being 121.52 (55-174) mm Hg 1.5 cm proximal to the hilar plate (P < 0.001). Mean pO2mt in the recipient's bile duct was 117.87 (62-185) mm Hg, while a value of 137.30 (81-198) mm Hg was observed 1.5 cm distal to the anastomosis (P < 0.001). Cystic duct resection (12 cases) was also related with higher pO2mt values at anastomosis [117.8 (93-157) vs 88.54 (31-124) mm Hg] and distal to anastomosis [135.6 (111-174) vs 106.2 (55-133) mm Hg; P < 0.001]. Patients with 1-, 3-, and 12-month biliary complications had significantly lower pO2mt in the intraoperative measurements. CONCLUSION Our preliminary results show that distal borders of donor and recipient bile ducts may be low-vascularized areas. Tissue pO2mt is significantly higher in areas close to the hilar plate and to the duodenum in donor and recipient's sides, respectively. Bile duct injury and biliary complications are associated with worse tissue pO2mt.
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Affiliation(s)
- Ruben Ciria
- Unit of Hepatobiliary Surgery and Liver Transplantation, University Hospital Reina Sofía, IMIBIC, Ciber-EHD, University of Cordoba, Cordoba, Spain
| | - Elena Navarro
- Unit of Hepatobiliary Surgery and Liver Transplantation, University Hospital Reina Sofía, IMIBIC, Ciber-EHD, University of Cordoba, Cordoba, Spain
| | | | - Ana-Belen Gallardo
- Unit of Hepatobiliary Surgery and Liver Transplantation, University Hospital Reina Sofía, IMIBIC, Ciber-EHD, University of Cordoba, Cordoba, Spain
| | - Javier Medina
- Unit of Hepatobiliary Surgery and Liver Transplantation, University Hospital Reina Sofía, IMIBIC, Ciber-EHD, University of Cordoba, Cordoba, Spain
| | - María-Dolores Ayllón
- Unit of Hepatobiliary Surgery and Liver Transplantation, University Hospital Reina Sofía, IMIBIC, Ciber-EHD, University of Cordoba, Cordoba, Spain
| | - Irene Gomez-Luque
- Unit of Hepatobiliary Surgery and Liver Transplantation, University Hospital Reina Sofía, IMIBIC, Ciber-EHD, University of Cordoba, Cordoba, Spain
| | - Juan Ruiz-Rabelo
- Unit of Hepatobiliary Surgery and Liver Transplantation, University Hospital Reina Sofía, IMIBIC, Ciber-EHD, University of Cordoba, Cordoba, Spain
| | - Antonio Luque
- Unit of Hepatobiliary Surgery and Liver Transplantation, University Hospital Reina Sofía, IMIBIC, Ciber-EHD, University of Cordoba, Cordoba, Spain
| | - Manuel de la Mata
- Liver Research Unit, University Hospital Reina Sofía, IMIBIC, Ciber-EHD, Cordoba, Spain
| | - Sebastián Rufián
- Unit of Hepatobiliary Surgery and Liver Transplantation, University Hospital Reina Sofía, IMIBIC, Ciber-EHD, University of Cordoba, Cordoba, Spain
| | - Pedro López-Cillero
- Unit of Hepatobiliary Surgery and Liver Transplantation, University Hospital Reina Sofía, IMIBIC, Ciber-EHD, University of Cordoba, Cordoba, Spain
| | - Javier Briceño
- Unit of Hepatobiliary Surgery and Liver Transplantation, University Hospital Reina Sofía, IMIBIC, Ciber-EHD, University of Cordoba, Cordoba, Spain
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20
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Ahmed EA, El-Badry AM, Mocchegiani F, Montalti R, Hassan AEA, Redwan AA, Vivarelli M. Impact of Graft Steatosis on Postoperative Complications after Liver Transplantation. Surg J (N Y) 2018; 4:e188-e196. [PMID: 30474065 PMCID: PMC6193803 DOI: 10.1055/s-0038-1675236] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2018] [Accepted: 08/30/2018] [Indexed: 02/07/2023] Open
Abstract
Background Steatotic grafts are more susceptible to ischemia-reperfusion injury than are normal grafts. Therefore, using steatotic grafts for liver transplantation (LT) is associated with high primary dysfunction and decreased survival rates. The aim of this study is to evaluate the impact of graft steatosis on post LT outcomes. Methods A retrospective cohort analysis of 271 LT recipients from 2005 to 2016 was performed and patients were classified based on two types of steatosis, macrosteatosis (MaS), and microsteatosis (MiS). Each category was subdivided into three groups according to the degree of steatosis: no (< 5%), mild (≥5 to < 30%), and moderate (≥30 to ≤60%). The primary hospital stays and 6-month postoperative complications were analyzed by the Clavien-Dindo classification system. Additionally, patient and graft survivals were studied. Results Significant differences were observed in grade III MaS ( p -value = 0.019) and grade V MiS ( p -value = 0.020). A high trend of early graft dysfunction was found in the moderate MaS and MiS groups; however, they were not statistically significant ( p -value = 0.199 and 0.282, respectively). Interestingly, the acute cellular rejection (ACR) rate was found to be inversely proportional to the degree of steatosis in both categories but it did not reach a significant level ( p -value = 0.161 and 0.111, respectively). Conclusion Excellent post LT long-term outcomes using grafts with mild and moderate steatosis were determined. Further studies are needed to evaluate the newly proposed relationship between ACR and steatosis.
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Affiliation(s)
- Emad Ali Ahmed
- Division of Hepatobiliary and Abdominal Transplantation Surgery, Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Ancona, Italy.,Division of Hepatobiliary and Pancreatic Surgery Unit, Department of General Surgery, University of Sohag, Sohag, Egypt
| | - Ashraf Mohammad El-Badry
- Division of Hepatobiliary and Pancreatic Surgery Unit, Department of General Surgery, University of Sohag, Sohag, Egypt
| | - Federico Mocchegiani
- Division of Hepatobiliary and Abdominal Transplantation Surgery, Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Ancona, Italy
| | - Roberto Montalti
- Division of Hepatobiliary and Abdominal Transplantation Surgery, Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Ancona, Italy
| | - Asem Elsani Ali Hassan
- Division of Hepatobiliary and Pancreatic Surgery Unit, Department of General Surgery, University of Sohag, Sohag, Egypt
| | - Alaa Ahmed Redwan
- Division of Hepatobiliary and Pancreatic Surgery Unit, Department of General Surgery, University of Sohag, Sohag, Egypt
| | - Marco Vivarelli
- Division of Hepatobiliary and Abdominal Transplantation Surgery, Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Ancona, Italy
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21
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Fujii Y, Nanashima A, Hiyoshi M, Imamura N, Yano K, Hamada T. Risk factors for hepatic insufficiency after major hepatectomy in non-cirrhotic patients. Asian J Surg 2018; 42:251-255. [PMID: 30170944 DOI: 10.1016/j.asjsur.2018.03.002] [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: 11/30/2017] [Revised: 01/24/2018] [Accepted: 03/05/2018] [Indexed: 10/28/2022] Open
Abstract
BACKGROUND Although recent advances in surgical techniques and perioperative management have reduced the morbidity and mortality after hepatectomy, hepatic insufficiency after major hepatectomy remains an important concern. This study aimed to clarify the risk factors for post-hepatectomy liver insufficiency. METHODS We enrolled 103 consecutive patients who underwent major hepatectomy which was defined as resection of four or more segments. Hepatic insufficiency is defined as an increase in serum total bilirubin after hepatectomy of 7 mg/dL or more, or death from multiple organ failure. We compared the patient disposition, demographics, perioperative factors such as surgical method, combined procedure, morbidity and so on between the patients with or without hepatic insufficiency. RESULTS Hepatic insufficiency occurred in 14 patients (14%) and six of them died during the hospital stay (6%). Risk factors by univariate analysis were the percentage of hepatic parenchyma to be resected (P = .025), combined procedure (P = .008) and postoperative morbidity excluding hepatic insufficiency (P < .001). A combined procedure (P = .036) and postoperative morbidity excluding hepatic insufficiency (P = .002) were a significant risk factor by multivariate analysis. CONCLUSION Unless remaining liver after hepatectomy has enough volume, combined procedure may account for hepatic insufficiency, which can follow the development of postoperative morbidity.
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Affiliation(s)
- Yoshiro Fujii
- Department of Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
| | - Atsushi Nanashima
- Department of Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Masahide Hiyoshi
- Department of Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Naoya Imamura
- Department of Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Koichi Yano
- Department of Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Takeomi Hamada
- Department of Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
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22
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Wu C, Lu C, Xu C. Short-term and long-term outcomes of liver transplantation using moderately and severely steatotic donor livers: A systematic review. Medicine (Baltimore) 2018; 97:e12026. [PMID: 30170411 PMCID: PMC6393101 DOI: 10.1097/md.0000000000012026] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND The aim of this study was to perform a systemic review of the studies addressing the use of moderately and severely steatotic donor livers for liver transplantation. METHODS We searched the following electronic databases from January 1, 1989, to August 1, 2017: PubMed, EMBASE, Science Citation Index Expanded, and the Cochrane Library. In addition, reference lists were scanned to identify any additional reports. The quality of published papers was assessed. The main outcomes of the use of moderately and severely steatotic donor livers for liver transplantation, including primary nonfunction, short-term mortality, and long-term mortality, were extracted for pooled analysis. RESULTS Literature searches identified 16 studies that met the inclusion criteria. There were no randomized controlled studies, and all of the studies were retrospective or prospective case series. From a total of 3226 subjects (532 moderately and severely steatotic donor livers and 2694 controls), we found a significant increase in primary nonfunction [odds ratio (OR): 2.47, 95% confidence interval (95% CI): 1.44-4.27], and a trend of increase in 1-month patient mortality (OR: 1.90, 95% CI: 0.98-3.71) with the use of moderately and severely steatotic donor livers, whereas the 1-year mortality was relatively less influenced. CONCLUSION The use of moderately and severely steatotic livers is associated with unfavorable short-term outcomes, but long-term outcomes are relatively less influenced.
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Affiliation(s)
| | - Chao Lu
- Department of Gastroenterology
| | - Chengfu Xu
- Department of Gastroenterology
- Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
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23
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Internal biliary stenting in liver transplantation. Langenbecks Arch Surg 2018; 403:487-494. [DOI: 10.1007/s00423-018-1669-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2018] [Accepted: 03/19/2018] [Indexed: 12/18/2022]
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24
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Yang L, Xin EY, Liao B, Lai LJ, Han M, Wang XP, Ju WQ, Wang DP, Guo ZY, He XS. Development and Validation of a Nomogram for Predicting Incidence of Early Allograft Dysfunction Following Liver Transplantation. Transplant Proc 2018; 49:1357-1363. [PMID: 28736007 DOI: 10.1016/j.transproceed.2017.03.083] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2017] [Accepted: 03/15/2017] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Early allograft dysfunction (EAD) is frequent complication post-liver transplantation and is closely related to recipient's mortality and morbidity. We sought to develop a nomogram for predicting incidence of EAD. METHODS Based on multivariate analysis of donor, recipient, and operation data of 199 liver transplants from deceased donors between 2013 and 2015, we identified 5 significant risk factors for EAD to build a nomogram. The model was subjected to prospective validation with a cohort of 42 patients who was recruited between January and June 2016. The predictive accuracy and discriminative ability were measured by area under the receiver operating characteristic curve (AUC). The agreement between nomogram prediction and actual observation was showed by the calibration curve. RESULTS Incidence rate of EAD in the training set and validation cohort were 55.91% (104/199) and 54.76% (23/42), respectively. In the training set, according to the results of univariable and multivariable analysis, 5 independent risk factors including donor gender, donor serum gamma-glutamyl transpeptidase level, donor serum urea level, donor comorbidities (respiratory, cardiac, and renal dysfunction), and recipient Model for End-stage Liver Disease score were identified and assembled into the nomogram. The AUC of internal validation using bootstrap resampling and prospective validation using the external cohort of 42 patients was 0.74 and 0.60, respectively. The calibration curves for probability of EAD showed acceptable agreement between nomogram prediction and actual observation. According to the score table, the probability of EAD was under 30% when the total point tally was under 72. But when the total was up to 139, the risk of EAD increased to 60%. CONCLUSION We've established and validated a nomogram that can provide individual prediction of EAD for liver transplant recipients. The practical prognostic model may help clinicians to qualify the liver graft accurately, making a more reasonable allocation of organs.
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Affiliation(s)
- L Yang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China; Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, China
| | - E Y Xin
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China; Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, China
| | - B Liao
- Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China; Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, China; Pathology Department, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - L J Lai
- Intensive Care Unit, Xin Yi People's Hospital, Xinyi, China
| | - M Han
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China; Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, China
| | - X P Wang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China; Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, China
| | - W Q Ju
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China; Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, China
| | - D P Wang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China; Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, China
| | - Z Y Guo
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China; Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, China.
| | - X S He
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China; Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, China.
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25
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Schlegel A, Scalera I, Perera MTPR, Kalisvaart M, Mergental H, Mirza DF, Isaac J, Muiesan P. Impact of donor age in donation after circulatory death liver transplantation: Is the cutoff "60" still of relevance? Liver Transpl 2018; 24:352-362. [PMID: 28885771 DOI: 10.1002/lt.24865] [Citation(s) in RCA: 75] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2017] [Revised: 06/19/2017] [Accepted: 08/24/2017] [Indexed: 02/07/2023]
Abstract
Advanced donor age has been identified as a risk factor when combined with donor warm ischemia time (WIT), eg, in donation after circulatory death (DCD). In several countries, DCD livers older than 60 years are not considered suitable due to concerns related to poor graft function and development of ischemic cholangiopathy. In this study, we evaluate outcomes after DCD liver transplantation using grafts from donors older than 60 years. We analyzed outcomes after DCD liver transplantation (n = 315), comparing donors > 60 years (n = 93) and donors ≤ 60 years (n = 222) from our center between 2005 and 2015. End points included graft function and complications and patient and graft survival. Multivariate risk analysis was performed to define further key factors that predicted inferior outcome. Donor age at the cutoff 60 years failed to stratify patient and graft survival. The rate of vascular, biliary, and overall complications was comparably low in both cohorts, and the median comprehensive complication index was 42.7 points, independent from the donor age. Second, donor body mass index (BMI) above a threshold of 25 kg/m2 significantly impacted on graft and patient survival at any donor age, whereas donor WIT and cold ischemia times were not predictive for graft loss. In conclusion, older DCD donors can be successfully used for liver transplantation with good longterm outcomes when further risk factors are limited. Additional risk is transmitted by an increased donor BMI regardless of donor age. Liver Transplantation 24 352-362 2018 AASLD.
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Affiliation(s)
- Andrea Schlegel
- The Liver Unit, Queen Elizabeth University Hospital Birmingham, Birmingham, UK.,National Institute for Health Research Liver Biomedical Research Unit, University Hospitals Birmingham, Birmingham, UK
| | - Irene Scalera
- The Liver Unit, Queen Elizabeth University Hospital Birmingham, Birmingham, UK
| | - M Thamara P R Perera
- The Liver Unit, Queen Elizabeth University Hospital Birmingham, Birmingham, UK.,National Institute for Health Research Liver Biomedical Research Unit, University Hospitals Birmingham, Birmingham, UK.,Department of Liver Surgery, Birmingham Children's Hospital National Health Service Foundation Trust, Birmingham, UK
| | - Marit Kalisvaart
- The Liver Unit, Queen Elizabeth University Hospital Birmingham, Birmingham, UK
| | - Hynek Mergental
- The Liver Unit, Queen Elizabeth University Hospital Birmingham, Birmingham, UK.,National Institute for Health Research Liver Biomedical Research Unit, University Hospitals Birmingham, Birmingham, UK
| | - Darius F Mirza
- The Liver Unit, Queen Elizabeth University Hospital Birmingham, Birmingham, UK.,National Institute for Health Research Liver Biomedical Research Unit, University Hospitals Birmingham, Birmingham, UK.,Department of Liver Surgery, Birmingham Children's Hospital National Health Service Foundation Trust, Birmingham, UK
| | - John Isaac
- The Liver Unit, Queen Elizabeth University Hospital Birmingham, Birmingham, UK.,Department of Liver Surgery, Birmingham Children's Hospital National Health Service Foundation Trust, Birmingham, UK
| | - Paolo Muiesan
- The Liver Unit, Queen Elizabeth University Hospital Birmingham, Birmingham, UK.,Department of Liver Surgery, Birmingham Children's Hospital National Health Service Foundation Trust, Birmingham, UK
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26
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Montalti R, Benedetti Cacciaguerra A, Nicolini D, Ahmed EA, Coletta M, De Pietri L, Risaliti A, Troisi RI, Mocchegiani F, Vivarelli M. Impact of aberrant left hepatic artery ligation on the outcome of liver transplantation. Liver Transpl 2018; 24:204-213. [PMID: 29211941 DOI: 10.1002/lt.24992] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2017] [Revised: 10/06/2017] [Accepted: 11/19/2017] [Indexed: 12/28/2022]
Abstract
The preservation of a graft's aberrant left hepatic artery (LHA) during liver transplantation (LT) ensures optimal vascularization of the left liver but can also be considered a risk factor for hepatic artery thrombosis (HAT). In contrast, ligation of an aberrant LHA may lead to hepatic ischemia with the potential risk of graft dysfunction and biliary complications. The aim of this study was to prospectively analyze the impact on the surgical strategy for LT of 5 tests performed to establish whether an aberrant LHA was an accessory or a replaced artery, thus leading to the design of a decisional algorithm. From August 2005 to December 2016, 395 whole LTs were performed in 376 patients. Five parameters were evaluated to determine whether an aberrant LHA was an accessory or a replaced artery. On the basis of our decision algorithm, an aberrant LHA was ligated during surgery when assessed as accessory and preserved when assessed as replaced. A total of 138 anatomical variants of hepatic arterial vascularization occurred in 120/395 (30.4%) grafts. Overall, the incidence of an aberrant LHA was 63/395 (15.9%). The LHA was ligated in 33 (52.4%) patients and preserved in 30 (47.6%) patients. After a mean follow-up period of 50.9 ± 39.7 months, the incidence of HAT, primary nonfunction, early allograft dysfunction, biliary stricture or leaks, and overall survival was similar in the 2 groups. In conclusion, once shown to be an accessory, an LHA can be safely ligated without clinical consequences on the outcome of LT. Liver Transplantation 24 204-213 2018 AASLD.
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Affiliation(s)
- Roberto Montalti
- Hepatobiliary and Abdominal Transplantation Surgery, Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Ancona, Italy
| | - Andrea Benedetti Cacciaguerra
- Hepatobiliary and Abdominal Transplantation Surgery, Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Ancona, Italy
| | - Daniele Nicolini
- Hepatobiliary and Abdominal Transplantation Surgery, Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Ancona, Italy
| | - Emad Alì Ahmed
- Hepatobiliary and Abdominal Transplantation Surgery, Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Ancona, Italy
- Hepatobiliary and Pancreatic Surgery Unit, General Surgery Department, Sohag University, Sohag, Egypt
| | - Martina Coletta
- Hepatobiliary and Abdominal Transplantation Surgery, Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Ancona, Italy
| | - Lesley De Pietri
- Anesthesiology and Intensive Care Unit, Arcispedale Santa Maria Nuova, Scientific Institute for Research, Hospitalization, and Health Care, Reggio Emilia, Italy
| | - Andrea Risaliti
- General Surgery and Transplantation Unit, Department of Medicine, University of Udine, Udine, Italy
| | - Roberto Ivan Troisi
- Department of General, Hepatobiliary and Liver Transplantation Surgery, Ghent University Hospital Medical School, Ghent, Belgium
| | - Federico Mocchegiani
- Hepatobiliary and Abdominal Transplantation Surgery, Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Ancona, Italy
| | - Marco Vivarelli
- Hepatobiliary and Abdominal Transplantation Surgery, Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Ancona, Italy
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27
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Posner AD, Sultan ST, Zaghloul NA, Twaddell WS, Bruno DA, Hanish SI, Hutson WR, Hebert L, Barth RN, LaMattina JC. Resolution of donor non-alcoholic fatty liver disease following liver transplantation. Clin Transplant 2017. [PMID: 28636211 DOI: 10.1111/ctr.13032] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Transplant surgeons conventionally select against livers displaying high degrees (>30%) of macrosteatosis (MaS), out of concern for primary non-function or severe graft dysfunction. As such, there is relatively limited experience with such livers, and the natural history remains incompletely characterized. We present our experience of transplanted livers with high degrees of MaS and microsteatosis (MiS), with a focus on the histopathologic and clinical outcomes. METHODS Twenty-nine cases were identified with liver biopsies available from both the donor and the corresponding liver transplant recipient. Donor liver biopsies displayed either MaS or MiS ≥15%, while all recipients received postoperative liver biopsies for cause. RESULTS The mean donor MaS and MiS were 15.6% (range 0%-60%) and 41.3% (7.5%-97.5%), respectively. MaS decreased significantly from donor (M=15.6%) to recipient postoperative biopsies (M=0.86%), P<.001. Similarly, MiS decreased significantly from donor biopsies (M=41.3%) to recipient postoperative biopsies (M=1.8%), P<.001. At a median of 68 days postoperatively (range 4-384), full resolution of MaS and MiS was observed in 27 of 29 recipients. CONCLUSIONS High degrees of MaS and MiS in donor livers resolve in recipients following liver transplantation. Further insight into the mechanisms responsible for treating fatty liver diseases could translate into therapeutic targets.
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Affiliation(s)
- Andrew D Posner
- University of Maryland School of Medicine, Baltimore, MD, USA
| | - Samuel T Sultan
- Division of Transplantation, University of Maryland School of Medicine, Baltimore, MD, USA
| | | | | | - David A Bruno
- Division of Transplantation, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Steven I Hanish
- Division of Transplantation, University of Maryland School of Medicine, Baltimore, MD, USA
| | | | - Laci Hebert
- Division of Transplantation, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Rolf N Barth
- Division of Transplantation, University of Maryland School of Medicine, Baltimore, MD, USA
| | - John C LaMattina
- Division of Transplantation, University of Maryland School of Medicine, Baltimore, MD, USA
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Management of biliary anastomotic strictures after liver transplantation. Transplant Rev (Orlando) 2017; 31:207-217. [DOI: 10.1016/j.trre.2017.03.002] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Revised: 02/06/2017] [Accepted: 03/19/2017] [Indexed: 12/13/2022]
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de Vries Y, von Meijenfeldt FA, Porte RJ. Post-transplant cholangiopathy: Classification, pathogenesis, and preventive strategies. Biochim Biophys Acta Mol Basis Dis 2017. [PMID: 28645651 DOI: 10.1016/j.bbadis.2017.06.013] [Citation(s) in RCA: 86] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Biliary complications are the most frequent cause of morbidity, re-transplantation, and even mortality after liver transplantation. In general, biliary leakage and anastomotic and non-anastomotic biliary strictures (NAS) can be recognized. There is no consensus on the exact definition of NAS and different names and criteria have been used in literature. We propose to use the term post-transplant cholangiopathy for the spectrum of abnormalities of large donor bile ducts, that includes NAS, but also intraductal casts and intrahepatic biloma formation, in the presence of a patent hepatic artery. Combinations of these manifestations of cholangiopathy are not infrequently found in the same liver and ischemia-reperfusion injury is generally considered the common underlying mechanism. Other factors that contribute to post-transplant cholangiopathy are biliary injury due to bile salt toxicity and immune-mediated injury. This review provides an overview of the various types of post-transplant cholangiopathy, the presumed pathogenesis, clinical implications, and preventive strategies.
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Affiliation(s)
- Yvonne de Vries
- Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands
| | - Fien A von Meijenfeldt
- Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands
| | - Robert J Porte
- Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands.
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Okamura Y, Hata K, Tanaka H, Hirao H, Kubota T, Inamoto O, Kageyama S, Tamaki I, Yermek N, Yoshikawa J, Uemoto S. Impact of Subnormothermic Machine Perfusion Preservation in Severely Steatotic Rat Livers: A Detailed Assessment in an Isolated Setting. Am J Transplant 2017; 17:1204-1215. [PMID: 27860296 DOI: 10.1111/ajt.14110] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2016] [Revised: 10/09/2016] [Accepted: 10/30/2016] [Indexed: 01/25/2023]
Abstract
The current drastic shortage of donor organs has led to acceptance of extended-criteria donors for transplantation, despite higher risk of primary nonfunction. Here, we report the impact of subnormothermic machine perfusion (SMP) preservation on the protection of >50% macrosteatotic livers. Dietary hepatic steatosis was induced in Wistar rats via 2-day fasting and subsequent 3-day re-feeding with a fat-free, carbohydrate-rich diet. This protocol induces 50-60% macrovesicular steatosis, which should be discarded when preserved via cold storage (CS). The fatty livers were retrieved and preserved for 4 h using either CS in histidine-tryptophan-ketoglutarate or SMP in polysol solution. Graft functional integrity was evaluated via oxygenated ex vivo reperfusion for 2 h at 37°C. SMP resulted in significant reductions in not only parenchymal alanine aminotransferase (p < 0.001), but also mitochondrial glutamate dehydrogenase (p < 0.001) enzyme release. Moreover, portal venous pressure (p = 0.047), tissue adenosine triphosphate (p = 0.001), bile production (p < 0.001), high-mobility group box protein-1 (p < 0.001), lipid peroxidation, and tissue glutathione were all significantly improved by SMP. Electron microscopy revealed that SMP alleviated deleterious alterations of sinusoidal microvasculature and hepatocellular mitochondria, both of which are characteristic disadvantages associated with steatosis. SMP could protect 50-60% macrosteatotic livers from preservation/reperfusion injury, and may thus represent a new means for expanding available donor pools.
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Affiliation(s)
- Y Okamura
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - K Hata
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - H Tanaka
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - H Hirao
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - T Kubota
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - O Inamoto
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - S Kageyama
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - I Tamaki
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - N Yermek
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - J Yoshikawa
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - S Uemoto
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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Tezcaner T, Dinç N, Y Karakayalı F, Kırnap M, Coşkun M, Moray G, Haberal M. Effect of Right Posterior Bile Duct Anatomy on Biliary Complications in Patients Undergoing Right Lobe Living Donor Liver Transplant. EXP CLIN TRANSPLANT 2017; 17:759-767. [PMID: 28128721 DOI: 10.6002/ect.2016.0200] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Our aim was to evaluate the influence of the localization of right posterior bile duct anatomy relative to portal vein of the donors on posttransplant bile duct complications. MATERIALS AND METHODS We retrospectively investigated 141 patients who had undergone living donor liver transplant using right hemiliver grafts. The patients were classified based on the pattern of the right posterior bile duct and divided into infraportal and supraportal types. Clinical donor and recipient risk factors and surgical outcomes were compared for their relationship with biliary complications using logistic regression analyses. RESULTS The 2 groups were similar according to demographic and clinical features. The biliary complication rate was 23.7% (9/38) in the infraportal group and 47.4% (37/78) in the supraportal group (P = .014). An analysis of risk factors for the development of anastomotic bile leak using logistic regression showed that a supraportal right posterior bile duct anatomy was a statistically significant positive predictor, with odds ratio of 18.905 (P = .012; confidence interval, 1.922-185.967). The distance of the right posterior bile duct from confluence was significantly lower in patients with biliary complications than in those without (mean of 7.66 vs 0.40 mm; P = .044). According to receiver operating characteristic analyses, the cut-off point for the length of right bile duct to right posterior bile duct from the hepatic confluence was 9.5 mm regarding presence of complications. CONCLUSIONS Factors influencing bile duct anastomosis leakage were supraportal-type donor bile duct anatomy and length of the right main bile duct from biliary confluence. Hepatic arterial complications were similarly a risk factor for biliary strictures. Because of the multiple factors leading to complications in living donor liver transplant, it is challenging to group these patients by operative risk; however, establishing risk models may facilitate the prediction of complications.
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Affiliation(s)
- Tugan Tezcaner
- From the Department of General Surgery, Başkent University, Ankara, Turkey
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Kaltenborn A, Gutcke A, Gwiasda J, Klempnauer J, Schrem H. Biliary complications following liver transplantation: Single-center experience over three decades and recent risk factors. World J Hepatol 2017; 9:147-154. [PMID: 28217251 PMCID: PMC5295148 DOI: 10.4254/wjh.v9.i3.147] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2016] [Revised: 11/09/2016] [Accepted: 11/29/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To identify independent risk factors for biliary complications in a center with three decades of experience in liver transplantation.
METHODS A total of 1607 consecutive liver transplantations were analyzed in a retrospective study. Detailed subset analysis was performed in 417 patients, which have been transplanted since the introduction of Model of End-Stage Liver Disease (MELD)-based liver allocation. Risk factors for the onset of anastomotic biliary complications were identified with multivariable binary logistic regression analyses. The identified risk factors in regression analyses were compiled into a prognostic model. The applicability was evaluated with receiver operating characteristic curve analyses. Furthermore, Kaplan-Meier analyses with the log rank test were applied where appropriate.
RESULTS Biliary complications were observed in 227 cases (14.1%). Four hundred and seventeen (26%) transplantations were performed after the introduction of MELD-based donor organ allocation. Since then, 21% (n = 89) of the patients suffered from biliary complications, which are further categorized into anastomotic bile leaks [46% (n = 41)], anastomotic strictures [25% (n = 22)], cholangitis [8% (n = 7)] and non-anastomotic strictures [3% (n = 3)]. The remaining 18% (n = 16) were not further classified. After adjustment for all univariably significant variables, the recipient MELD-score at transplantation (P = 0.006; OR = 1.035; 95%CI: 1.010-1.060), the development of hepatic artery thrombosis post-operatively (P = 0.019; OR = 3.543; 95%CI: 1.233-10.178), as well as the donor creatinine prior to explantation (P = 0.010; OR = 1.003; 95%CI: 1.001-1.006) were revealed as independent risk factors for biliary complications. The compilation of these identified risk factors into a prognostic model was shown to have good prognostic abilities in the investigated cohort with an area under the receiver operating curve of 0.702.
CONCLUSION The parallel occurrence of high recipient MELD and impaired donor kidney function should be avoided. Risk is especially increased when post-transplant hepatic artery thrombosis occurs.
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Obed A, Bashir A, Jarrad A. Rapid Virological Response After Early Treatment with a Combined Therapy of Ledipasvir and Sofosbuvir in HCV Genotype 4 After Living Donor Liver Transplantation in a HCC Downstaged Patient: Case Report and Review of the Literature. AMERICAN JOURNAL OF CASE REPORTS 2016; 17:672-5. [PMID: 27647003 PMCID: PMC5031172 DOI: 10.12659/ajcr.898594] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Patient: Male, 54 Final Diagnosis: HCC with portal vein Symptoms: Liver failure Medication: — Clinical Procedure: Hepatitis c treatment • hcc tratment Specialty: Transplantology
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Affiliation(s)
- Aiman Obed
- Department of Hepatobiliary and Transplant Surgery, Jordan Hospital, Amman, Jordan
| | - Abdalla Bashir
- Department of General and Transplant SurgerySurgery, Jordan Hospital, Amman, Jordan
| | - Anwar Jarrad
- Department of Gastroenterology and Hepatology, Jordan Hospital, Amman, Jordan
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34
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Nemes B, Gámán G, Polak WG, Gelley F, Hara T, Ono S, Baimakhanov Z, Piros L, Eguchi S. Extended-criteria donors in liver transplantation Part II: reviewing the impact of extended-criteria donors on the complications and outcomes of liver transplantation. Expert Rev Gastroenterol Hepatol 2016; 10:841-59. [PMID: 26831547 DOI: 10.1586/17474124.2016.1149062] [Citation(s) in RCA: 66] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Extended-criteria donors (ECDs) have an impact on early allograft dysfunction (EAD), biliary complications, relapse of hepatitis C virus (HCV), and survivals. Early allograft dysfunction was frequently seen in grafts with moderate and severe steatosis. Donors after cardiac death (DCD) have been associated with higher rates of graft failure and biliary complications compared to donors after brain death. Extended warm ischemia, reperfusion injury and endothelial activation trigger a cascade, leading to microvascular thrombosis, resulting in biliary necrosis, cholangitis, and graft failure. The risk of HCV recurrence increased by donor age, and associated with using moderately and severely steatotic grafts. With the administration of protease inhibitors sustained virological response was achieved in majority of the patients. Donor risk index and EC donor scores (DS) are reported to be useful, to assess the outcome. The 1-year survival rates were 87% and 40% respectively, for donors with a DS of 0 and 3. Graft survival was excellent up to a DS of 2, however a DS >2 should be avoided in higher-risk recipients. The 1, 3 and 5-year survival of DCD recipients was comparable to optimal donors. However ECDs had minor survival means of 85%, 78.6%, and 72.3%. The graft survival of split liver transplantation (SLT) was comparable to that of whole liver orthotopic liver transplantation. SLT was not regarded as an ECD factor in the MELD era any more. Full-right-full-left split liver transplantation has a significant advantage to extend the high quality donor pool. Hypothermic oxygenated machine perfusion can be applied clinically in DCD liver grafts. Feasibility and safety were confirmed. Reperfusion injury was also rare in machine perfused DCD livers.
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Affiliation(s)
- Balázs Nemes
- a Department of Organ Transplantation, Faculty of Medicine, Institute of Surgery , University of Debrecen , Debrecen , Hungary
| | - György Gámán
- b Clinic of Transplantation and Surgery , Semmelweis University , Budapest , Hungary
| | - Wojciech G Polak
- c Department of Surgery, Division of Hepatopancreatobiliary and Transplant Surgery, Erasmus MC , University Medical Center Rotterdam , Rotterdam , The Netherlands
| | - Fanni Gelley
- d Dept of Internal medicine and Gastroenterology , Polyclinic of Hospitallers Brothers of St. John of God , Budapest , Hungary
| | - Takanobu Hara
- e Department of Surgery , Nagasaki University Graduate School of Biomedical Sciences , Nagasaki , Japan
| | - Shinichiro Ono
- e Department of Surgery , Nagasaki University Graduate School of Biomedical Sciences , Nagasaki , Japan
| | - Zhassulan Baimakhanov
- e Department of Surgery , Nagasaki University Graduate School of Biomedical Sciences , Nagasaki , Japan
| | - Laszlo Piros
- b Clinic of Transplantation and Surgery , Semmelweis University , Budapest , Hungary
| | - Susumu Eguchi
- e Department of Surgery , Nagasaki University Graduate School of Biomedical Sciences , Nagasaki , Japan
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35
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Nemes B, Gámán G, Polak WG, Gelley F, Hara T, Ono S, Baimakhanov Z, Piros L, Eguchi S. Extended criteria donors in liver transplantation Part I: reviewing the impact of determining factors. Expert Rev Gastroenterol Hepatol 2016; 10:827-39. [PMID: 26838962 DOI: 10.1586/17474124.2016.1149061] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The definition and factors of extended criteria donors have already been set; however, details of the various opinions still differ in many respects. In this review, we summarize the impact of these factors and their clinical relevance. Elderly livers must not be allocated for hepatitis C virus (HCV) positives, or patients with acute liver failure. In cases of markedly increased serum transaminases, donor hemodynamics is an essential consideration. A prolonged hypotension of the donor does not always lead to an increase in post-transplantation graft loss if post-OLT care is proper. Hypernatremia of less than 160 mEq/L is not an absolute contraindication to accept a liver graft per se. The presence of steatosis is an independent and determinant risk factor for the outcome. The gold standard of the diagnosis is the biopsy. This is recommended in all doubtful cases. The use of HCV+ grafts for HCV+ recipients is comparable in outcome. The leading risk factor for HCV recurrence is the actual RNA positivity of the donor. The presence of a proper anti-HBs level seems to protect from de novo HBV infection. A favourable outcome can be expected if a donation after cardiac death liver is transplanted in a favourable condition, meaning, a warm ischemia time < 30 minutes, cold ischemia time < 8-10 hours, and donor age 50-60 years. The pathway of organ quality assessment is to obtain the most relevant information (e.g. biopsy), consider the co-existing donor risk factors and the reserve capacity of the recipient, and avoid further technical issues.
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Affiliation(s)
- Balázs Nemes
- a Department of Organ Transplantation, Faculty of Medicine , Institute of Surgery, University of Debrecen , Debrecen , Hungary
| | - György Gámán
- b Clinic of Transplantation and Surgery , Semmelweis University , Budapest , Hungary
| | - Wojciech G Polak
- c Department of Surgery, Division of Hepatopancreatobiliary and Transplant Surgery, Erasmus MC , University Medical Center Rotterdam , Rotterdam , The Netherlands
| | - Fanni Gelley
- d Department of Internal medicine and Gastroenterology , Polyclinic of Hospitallers Brothers of St. John of God , Budapest , Hungary
| | - Takanobu Hara
- e Department of Surgery , Nagasaki University Graduate School of Biomedical Sciences , Nagasaki , Japan
| | - Shinichiro Ono
- e Department of Surgery , Nagasaki University Graduate School of Biomedical Sciences , Nagasaki , Japan
| | - Zhassulan Baimakhanov
- e Department of Surgery , Nagasaki University Graduate School of Biomedical Sciences , Nagasaki , Japan
| | - Laszlo Piros
- b Clinic of Transplantation and Surgery , Semmelweis University , Budapest , Hungary
| | - Susumu Eguchi
- e Department of Surgery , Nagasaki University Graduate School of Biomedical Sciences , Nagasaki , Japan
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36
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Wong TCL, Fung JYY, Chok KSH, Cheung TT, Chan ACY, Sharr WW, Dai WC, Chan SC, Lo CM. Excellent outcomes of liver transplantation using severely steatotic grafts from brain-dead donors. Liver Transpl 2016; 22:226-36. [PMID: 26359934 DOI: 10.1002/lt.24335] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2015] [Revised: 09/04/2015] [Accepted: 09/06/2015] [Indexed: 12/15/2022]
Abstract
Liver grafts with macrovesicular steatosis of > 60% are considered unsuitable for deceased donor liver transplantation (DDLT) because of the unacceptably high risk of primary nonfunction (PNF) and graft loss. This study reports our experience in using such grafts from brain-dead donors. Prospectively collected data of DDLT recipient outcomes from 1991 to 2013 were retrospectively analyzed. Macrovesicular steatosis > 60% at postperfusion graft biopsy was defined as severe steatosis. In total, 373 patients underwent DDLT. Nineteen patients received severely steatotic grafts (ie, macrovesicular steatosis > 60%), and 354 patients had grafts with ≤ 60% steatosis (control group). Baseline demographics were comparable except that recipient age was older in the severe steatosis group (51 versus 55 years; P = 0.03). Median Model for End-Stage Liver Disease (MELD) score was 20 in the severe steatosis group and 22 in the control group. Cold ischemia time (CIT) was 384 minutes in the severe steatosis group and 397.5 minutes in the control group (P = 0.66). The 2 groups were similar in duration of stay in the hospital and in the intensive care unit. Risk of early allograft dysfunction (0/19 [0%] versus 1/354 [0.3%]; P>0.99) and 30-day mortality (0/19 [0%] versus 11/354 [3.1%]; P = 0.93) were also similar between groups. No patient developed PNF. The 1-year and 3-year overall survival rates in the severe steatosis group were both 94.7%. The corresponding rates in the control group were 91.8% and 85.8% (P = 0.55). The use of severely steatotic liver grafts from low-risk donors was safe, and excellent outcomes were achieved; however, these grafts should be used with caution, especially in patients with high MELD score. Keeping a short CIT was crucial for the successful use of such grafts in liver transplantation.
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Affiliation(s)
- Tiffany C L Wong
- Departments of Surgery, The University of Hong Kong, Pokfulam, Hong Kong
| | - James Y Y Fung
- Departments of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong
| | - Kenneth S H Chok
- Departments of Surgery, The University of Hong Kong, Pokfulam, Hong Kong
| | - Tan To Cheung
- Departments of Surgery, The University of Hong Kong, Pokfulam, Hong Kong
| | - Albert C Y Chan
- Departments of Surgery, The University of Hong Kong, Pokfulam, Hong Kong
| | - William W Sharr
- Departments of Surgery, The University of Hong Kong, Pokfulam, Hong Kong
| | - Wing Chiu Dai
- Departments of Surgery, The University of Hong Kong, Pokfulam, Hong Kong
| | - See Ching Chan
- Departments of Surgery, The University of Hong Kong, Pokfulam, Hong Kong
| | - Chung Mau Lo
- Departments of Surgery, The University of Hong Kong, Pokfulam, Hong Kong
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Gastaca M, Matarranz A, Martinez L, Valdivieso A, Ruiz P, Ventoso A, Fernandez JR, Palomares I, Prieto M, Suarez MJ, Ortiz de Urbina J. Risk factors for biliary complications after orthotopic liver transplantation with T-tube: a single-center cohort of 743 transplants. Transplant Proc 2015; 46:3097-9. [PMID: 25420833 DOI: 10.1016/j.transproceed.2014.09.173] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND Despite recent advances in organ preservation, surgical procedures, and immunosuppression, biliary reconstruction after orthotopic liver transplantation (OLT) remains as a major source of morbidity. The purpose of this study was to identify risk factors for the development of biliary complications (BCs) after end-to-end choledochocholedochostomy (EE-CC) with a T-tube as the standard technique for biliary reconstruction after OLT. METHODS A total of 833 consecutive liver transplantations that took place from February 1996 to April 2010 were retrospectively reviewed. Patients with concomitant hepatic artery complications were excluded, as were those who underwent urgent retransplantation or died within 1 week after transplantation. Finally, the study group comprised 743 patients. RESULTS The overall BC rate was 9.8% (73 patients), including stricture in 19 patients (2.6%) and bile leakage in 39 patients (5.2%). After univariate analysis, significant risk factors for BCs were surgery time >5 hours, arterial ischemia time >30 minutes, use of a classic transplant technique, transfusion of red blood cells ≥5 units, anti-cytomegalovirus treatment, and period of transplantation between 1996 and 2002. Stepwise logistic regression study was performed, including those variables with a value of P <.200. Multivariate analysis showed that pretransplant serum creatinine (odds ratio = 1.27; 95% confidence interval [CI], 1.03-1.57; P = .025) and arterial ischemia time >30 minutes (odds ratio = 2.44; 95% CI, 1.45-4.12; P = .001) were the only independent risk factors related to the development of BCs after biliary reconstruction with the T-tube. CONCLUSIONS The performance of different variables in predicting occurrence of BCs was assessed with the use of receiver operating characteristic analysis. The area under the receiver operating characteristic curve of our model was 0.637 (95% CI, 0.564-0.710), and therefore we must conclude that other variables not included in our model may have influence in the development of BCs after OLT with an EE-CC with a T-tube as the procedure for biliary reconstruction.
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Affiliation(s)
- M Gastaca
- Hepatobiliary Surgery and Liver Transplantation Unit, Cruces University Hospital, University of the Basque Country, Bilbao, Spain.
| | - A Matarranz
- Hepatobiliary Surgery and Liver Transplantation Unit, Cruces University Hospital, Bilbao, Spain
| | - L Martinez
- Hepatology Unit, Cruces University Hospital, Bilbao, Spain
| | - A Valdivieso
- Hepatobiliary Surgery and Liver Transplantation Unit, Cruces University Hospital, University of the Basque Country, Bilbao, Spain
| | - P Ruiz
- Hepatobiliary Surgery and Liver Transplantation Unit, Cruces University Hospital, Bilbao, Spain
| | - A Ventoso
- Hepatobiliary Surgery and Liver Transplantation Unit, Cruces University Hospital, University of the Basque Country, Bilbao, Spain
| | - J R Fernandez
- Hepatology Unit, Cruces University Hospital, Bilbao, Spain
| | - I Palomares
- Hepatobiliary Surgery and Liver Transplantation Unit, Cruces University Hospital, University of the Basque Country, Bilbao, Spain
| | - M Prieto
- Hepatobiliary Surgery and Liver Transplantation Unit, Cruces University Hospital, University of the Basque Country, Bilbao, Spain
| | - M J Suarez
- Hepatology Unit, Cruces University Hospital, Bilbao, Spain
| | - J Ortiz de Urbina
- Hepatobiliary Surgery and Liver Transplantation Unit, Cruces University Hospital, University of the Basque Country, Bilbao, Spain
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Simoes P, Kesar V, Ahmad J. Spectrum of biliary complications following live donor liver transplantation. World J Hepatol 2015; 7:1856-1865. [PMID: 26207167 PMCID: PMC4506943 DOI: 10.4254/wjh.v7.i14.1856] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2014] [Revised: 01/22/2015] [Accepted: 07/08/2015] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation is the optimal treatment for many patients with advanced liver disease, including decompensated cirrhosis, hepatocellular carcinoma and acute liver failure. Organ shortage is the main determinant of death on the waiting list and hence living donor liver transplantation (LDLT) assumes importance. Biliary complications are the most common post operative morbidity after LDLT and occur due to anatomical and technical reasons. They include biliary leaks, strictures and cast formation and occur in the recipient as well as the donor. The types of biliary complications after LDLT along with their etiology, presenting features, diagnosis and endoscopic and surgical management are discussed.
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Wang JZ, Liu Y, Wang JL, Lu L, Zhang YF, Lu HW, Li YM. Sequential vs simultaneous revascularization in patients undergoing liver transplantation: A meta-analysis. World J Gastroenterol 2015; 21:7036-46. [PMID: 26078582 PMCID: PMC4462746 DOI: 10.3748/wjg.v21.i22.7036] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2014] [Revised: 01/08/2015] [Accepted: 02/05/2015] [Indexed: 02/06/2023] Open
Abstract
AIM We undertook this meta-analysis to investigate the relationship between revascularization and outcomes after liver transplantation. METHODS A literature search was performed using MeSH and key words. The quality of the included studies was assessed using the Jadad Score and the Newcastle-Ottawa Scale. Heterogeneity was evaluated by the χ(2) and I (2) tests. The risk of publication bias was assessed using a funnel plot and Egger's test, and the risk of bias was assessed using a domain-based assessment tool. A sensitivity analysis was conducted by reanalyzing the data using different statistical approaches. RESULTS Six studies with a total of 467 patients were included. Ischemic-type biliary lesions were significantly reduced in the simultaneous revascularization group compared with the sequential revascularization group (OR = 4.97, 95%CI: 2.45-10.07; P < 0.00001), and intensive care unit (ICU) days were decreased (MD = 2.00, 95%CI: 0.55-3.45; P = 0.007) in the simultaneous revascularization group. Although warm ischemia time was prolonged in simultaneous revascularization group (MD = -25.84, 95%CI: -29.28-22.40; P < 0.00001), there were no significant differences in other outcomes between sequential and simultaneous revascularization groups. Assessment of the risk of bias showed that the methods of random sequence generation and blinding might have been a source of bias. The sensitivity analysis strengthened the reliability of the results of this meta-analysis. CONCLUSION The results of this study indicate that simultaneous revascularization in liver transplantation may reduce the incidence of ischemic-type biliary lesions and length of stay of patients in the ICU.
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Xia W, Ke Q, Wang Y, Feng X, Guo H, Wang W, Zhang M, Shen Y, Wu J, Xu X, Yan S, Zheng S. Donation after cardiac death liver transplantation: Graft quality evaluation based on pretransplant liver biopsy. Liver Transpl 2015; 21:838-46. [PMID: 25824672 DOI: 10.1002/lt.24123] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2014] [Accepted: 03/18/2015] [Indexed: 02/05/2023]
Abstract
Donation after cardiac death (DCD) liver grafts are associated with inferior clinical outcomes and high discard rates because of poor graft quality. We investigated the predictive value of DCD liver biopsy for the pretransplant graft quality evaluation. DCD liver transplants that took place between October 2010 and April 2014 were included (n = 127). Histological features of graft biopsy samples were analyzed to assess risk factors for graft survival. Macrovesicular steatosis ≥ 20% [hazard ratio (HR) = 2.973; P = 0.045] and sinusoidal neutrophilic infiltrate (HR = 6.969; P = 0.005) were confirmed as independent risk factors for graft survival; hepatocellular swelling, vacuolation, and necrosis failed to show prognostic value. Additionally, a donor serum total bilirubin level ≥ 34.2 μmol/L was also associated with a lower probability of graft survival. Our analysis indicates that macrovesicular steatosis ≥ 20% and sinusoidal neutrophilic infiltrate are novel and useful histological markers for DCD liver grafts with unacceptable quality. This finding can be used by transplant surgeons to improve DCD liver acceptance protocols.
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Affiliation(s)
- Weiliang Xia
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Zhejiang University, Hangzhou, China
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Qinghong Ke
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Zhejiang University, Hangzhou, China
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Ye Wang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Zhejiang University, Hangzhou, China
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Xiaowen Feng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Zhejiang University, Hangzhou, China
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Haijun Guo
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Zhejiang University, Hangzhou, China
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Weilin Wang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Zhejiang University, Hangzhou, China
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Min Zhang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Zhejiang University, Hangzhou, China
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yan Shen
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Zhejiang University, Hangzhou, China
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Jian Wu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Zhejiang University, Hangzhou, China
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Xiao Xu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Zhejiang University, Hangzhou, China
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Sheng Yan
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Zhejiang University, Hangzhou, China
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Zhejiang University, Hangzhou, China
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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Clinical outcomes and costs associated with in-hospital biliary complications after liver transplantation: a cross-sectional analysis. J Gastrointest Surg 2015; 19:282-9. [PMID: 25319035 PMCID: PMC4305464 DOI: 10.1007/s11605-014-2675-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2014] [Accepted: 10/06/2014] [Indexed: 01/31/2023]
Abstract
INTRODUCTION In-hospital biliary complications (BCs) after liver transplantation (LT) are reported in up to 20 % of patients and contribute to poor outcomes and increased costs. Existing single-center outcome and cost analyses studies are limited in scope. METHODS This is a cross-sectional analysis of national data involving 7,967 patients transplanted between 2011 and 2012 with the primary aim of determining the association between BCs and clinical outcomes and costs. Age, race, diagnosis, and severity of illness are associated with the development of BCs. RESULTS BCs develop in 14.6 % of LT recipients and have substantial implications for perioperative outcomes, including length of hospital and ICU stay (27.9 vs 19.6 mean days, p < 0.001 and 12.0 vs 8.3 mean days, p < 0.001, respectively), in-hospital morbidity (39 vs 27 %, p < 0.001), 30-day readmissions (14.8 vs 11.2 %, p < 0.001), and in-hospital mortality (5.8 vs 4.0 %, p < 0.001). BCs contributed to a mean increase in in-hospital costs of $36,212 (p < 0.001), due to increases in accommodations ($9,539, p < 0.001), surgical services ($3,988, p < 0.001), and pharmacy services ($8,445, p < 0.001). DISCUSSION BCs are a predominant etiology for in-hospital morbidity and mortality, while contributing significantly to the high cost of LT. Efforts should be focused on understanding salient and modifiable risk factors, while developing innovative strategies to reduce BCs.
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McElroy LM, Daud A, Davis AE, Lapin B, Baker T, Abecassis MM, Levitsky J, Holl JL, Ladner DP. A meta-analysis of complications following deceased donor liver transplant. Am J Surg 2014; 208:605-18. [PMID: 25118164 DOI: 10.1016/j.amjsurg.2014.06.006] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2014] [Revised: 05/14/2014] [Accepted: 06/09/2014] [Indexed: 12/21/2022]
Abstract
BACKGROUND Liver transplantation is a complex surgery associated with high rates of postoperative complications. While national outcomes data are available, national rates of most complications are unknown. DATA SOURCES A systematic review of the literature reporting rates of postoperative complications between 2002 and 2012 was performed. A cohort of 29,227 deceased donor liver transplant recipients from 74 studies was used to calculate pooled incidences for 17 major postoperative complications. CONCLUSIONS This is the first comprehensive review of postoperative complications after liver transplantation and can serve as a guide for transplant and nontransplant clinicians. Efforts to collect national data on complications, such as through the National Surgical Quality Improvement Program, would improve the ability to provide patients with informed consent, serve as a tool for individual center performance monitoring, and provide a central source against which to measure interventions aimed at improving patient care.
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Affiliation(s)
- Lisa M McElroy
- Center for Healthcare Studies, Institute for Public Health and Medicine, Chicago, IL, USA; Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Chicago, IL, USA.
| | - Amna Daud
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Chicago, IL, USA
| | - Ashley E Davis
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Chicago, IL, USA
| | - Brittany Lapin
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Chicago, IL, USA
| | - Talia Baker
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Chicago, IL, USA
| | - Michael M Abecassis
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Chicago, IL, USA
| | - Josh Levitsky
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Chicago, IL, USA
| | - Jane L Holl
- Center for Healthcare Studies, Institute for Public Health and Medicine, Chicago, IL, USA
| | - Daniela P Ladner
- Center for Healthcare Studies, Institute for Public Health and Medicine, Chicago, IL, USA; Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Chicago, IL, USA
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Mourad MM, Algarni A, Liossis C, Bramhall SR. Aetiology and risk factors of ischaemic cholangiopathy after liver transplantation. World J Gastroenterol 2014; 20:6159-6169. [PMID: 24876737 PMCID: PMC4033454 DOI: 10.3748/wjg.v20.i20.6159] [Citation(s) in RCA: 85] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Revised: 01/26/2014] [Accepted: 03/19/2014] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation (LT) is the best treatment for end-stage hepatic failure, with an excellent survival rates over the last decade. Biliary complications after LT pose a major challenge especially with the increasing number of procured organs after circulatory death. Ischaemic cholangiopathy (IC) is a set of disorders characterized by multiple diffuse strictures affecting the graft biliary system in the absence of hepatic artery thrombosis or stenosis. It commonly presents with cholestasis and cholangitis resulting in higher readmission rates, longer length of stay, repeated therapeutic interventions, and eventually re-transplantation with consequent effects on the patient’s quality of life and increased health care costs. The pathogenesis of IC is unclear and exhibits a higher prevalence with prolonged ischaemia time, donation after circulatory death (DCD), rejection, and cytomegalovirus infection. The majority of IC occurs within 12 mo after LT. Prolonged warm ischaemic times predispose to a profound injury with a subsequently higher prevalence of IC. Biliary complications and IC rates are between 16% and 29% in DCD grafts compared to between 3% and 17% in donation after brain death (DBD) grafts. The majority of ischaemic biliary lesions occur within 30 d in DCD compared to 90 d in DBD grafts following transplantation. However, there are many other risk factors for IC that should be considered. The benefits of DCD in expanding the donor pool are hindered by the higher incidence of IC with increased rates of re-transplantation. Careful donor selection and procurement might help to optimize the utilization of DCD grafts.
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44
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Gunay Y, Guler N, Dayangac M, Taskesen F, Yaprak O, Emek E, Akyildiz M, Altaca G, Yuzer Y, Tokat Y. Living donor liver transplantation for obese patients: challenges and outcomes. Liver Transpl 2014; 20:311-22. [PMID: 24243642 DOI: 10.1002/lt.23794] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2013] [Revised: 10/22/2013] [Accepted: 11/09/2013] [Indexed: 12/13/2022]
Abstract
Living donor liver transplantation (LDLT) is an accepted option for end-stage liver disease, particularly in countries in which there are organ shortages. However, little is known about LDLT for obese patients. We sought to determine the effects of obesity on pretransplant living donor selection for obese recipients and their outcomes. On the basis of body mass index (BMI) values, 148 patients were classified as normal weight (N), 148 were classified as overweight (OW), and 74 were classified as obese (O). O recipients had significantly greater BMI values (32.1 ± 1.6 versus 23.2 ± 1.9 kg/m(2), P < 0.001) and received larger actual grafts (918.9 ± 173 versus 839.4 ± 162 g, P = 0.002) than recipients with normal BMI values. Donors who donated to O recipients had a greater mean BMI (26.3 ± 3.8 kg/m(2)) than those who donated to N recipients (24.4 ± 3.2 kg/m(2), P = 0.001). Although O recipients were more likely to face some challenges in finding a suitable living donor, there were no differences in graft survival [hazard ratio (HR) = 0.955, 95% confidence interval (CI) = 0.474-1.924, P = 0.90] or recipient survival (HR = 0.90, 95% CI = 0.56-1.5, P = 0.67) between the 3 groups according to an adjusted Cox proportional hazards model. There were no significant differences in posttransplant complication rates between the 3 recipient groups or in the morbidity rates for the donors who donated to O recipients versus the donors who donated to OW and N recipients (P = 0.26). Therefore, we recommend that obese patients undergo pretransplant evaluations. If they are adequately evaluated and selected, they should be considered for LDLT.
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Affiliation(s)
- Yusuf Gunay
- Liver Transplantation Center, Florence Nightingale Hospital, Istanbul, Turkey
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45
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Chavin KD, Taber DJ, Norcross M, Pilch NA, Crego H, McGillicuddy JW, Bratton CF, Lin A, Baliga PK. Safe use of highly steatotic livers by utilizing a donor/recipient clinical algorithm. Clin Transplant 2013; 27:732-41. [PMID: 23991646 DOI: 10.1111/ctr.12211] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/18/2013] [Indexed: 01/23/2023]
Abstract
The aim of this study was to assess the long-term safety and clinical outcomes associated with the utilization of highly steatotic donor livers utilizing a specific donor/recipient matching algorithm. This was a prospective, observational, single-center, 10-yr follow-up study. Highly steatotic livers were utilized according to a donor/recipient algorithm that guided the surgeon to use highly steatotic donor organs judiciously in low-risk recipients. This study initially compared fat assessment based on frozen-section Ehrlich's hematoxylin and eosin (H&E) to reperfusion biopsy fat assessment and demonstrated that H&E is an insensitive analysis to determine degree of steatosis. Patients were divided into three groups based on donor steatosis (group 1: <30% steatosis, group 2: 30-60% steatosis, group 3: >60% steatosis), and clinical outcomes were assessed. One hundred and sixteen patients were included in the analysis. Patients that received severely steatotic livers (>60% fat) showed increased reperfusion liver injury and delayed return of liver function in the early postoperative period, demonstrated by biochemical markers. However, there were no differences in primary non-function, postoperative complications, length of stay, and patient and graft survival. Using rigorous donor/recipient matching through a detailed algorithm, these data demonstrate that normal liver allograft outcomes are not superior to those in highly steatotic grafts.
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Affiliation(s)
- Kenneth D Chavin
- Division of Transplantation, Department of Surgery, Medical University of South Carolina, Charleston, SC, USA
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Frongillo F, Grossi U, Lirosi MC, Nure E, Sganga G, Avolio AW, Inchingolo R, Di Stasi C, Rinaldi P, Agnes S. Incidence, management, and results of hepatic artery stenosis after liver transplantation in the era of donor to recipient match. Transplant Proc 2013; 45:2722-5. [PMID: 24034032 DOI: 10.1016/j.transproceed.2013.08.007] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Hepatic artery stenosis (HAS) is an important complication after liver transplantation. However, studies are not conclusive in terms of definition, incidence, best treatment, and timing of intervention. The aim of this study was to evaluate the incidence of SSHA that occurred in a single center over the past 12 years, pointing out diagnostic and therapeutic strategies. METHODS The incidence of HAS was reviewed in 258 liver transplant recipients between January 1999 and December 2011. All patients underwent Doppler ultrasound (DUS) at fixed times. Multidetector computed tomographic angiography (MDCTA) was performed to confirm the DUS findings. RESULTS HAS occurred in 23 cases (9.3%). In all cases diagnosis was performed by DUS resulting in a sensitivity of 100% and a specificity of 99.6%. Based on DUS and MDCTA data integration, in 10 cases we adopted the "wait and see" strategy, whereas 13 patients underwent interventional radiology techniques. CONCLUSION DUS monitoring is efficacious in the diagnosis of HAS after liver transplantation. Interventional radiology procedures are safe and efficacious.
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Affiliation(s)
- F Frongillo
- Division of General Surgery and Organ's Transplantation Service, Department of Surgical Sciences, Catholic University, "A. Gemelli" University Hospital, Largo A. Gemelli, 8 - 00168 Rome, Italy; Department of Bioimaging and Radiological Sciences, Catholic University, "A. Gemelli" University Hospital, Largo A. Gemelli, 8 - 00168 Rome, Italy.
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Brunner SM, Junger H, Ruemmele P, Schnitzbauer AA, Doenecke A, Kirchner GI, Farkas SA, Loss M, Scherer MN, Schlitt HJ, Fichtner-Feigl S. Bile duct damage after cold storage of deceased donor livers predicts biliary complications after liver transplantation. J Hepatol 2013; 58:1133-9. [PMID: 23321317 DOI: 10.1016/j.jhep.2012.12.022] [Citation(s) in RCA: 83] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2012] [Revised: 12/12/2012] [Accepted: 12/22/2012] [Indexed: 12/18/2022]
Abstract
BACKGROUND & AIMS The aim of this study was to examine the development of biliary epithelial damage between organ retrieval and transplantation and its clinical relevance for patients. METHODS Common bile duct samples during donor hepatectomy, after cold storage, and after reperfusion were compared to healthy controls by hematoxylin and eosin (H&E) staining and immunofluorescence for tight junction protein 1 and Claudin-1. A bile duct damage score to quantify biliary epithelial injury was developed and correlated with recipient and donor data and patient outcome. RESULTS Control (N=16) and donor hepatectomy bile ducts (N=10) showed regular epithelial morphology and tight junction architecture. After cold storage (N=37; p=0.0119), and even more after reperfusion (N=62; p=0.0002), epithelial damage, as quantified by the bile duct damage score, was markedly increased, and both tight junction proteins were detected with inappropriate morphology. Patients with major bile duct damage after cold storage had a significantly increased risk of biliary complications (relative risk 18.75; p<0.0001) and graft loss (p=0.0004). CONCLUSIONS In many cases, the common bile duct epithelium shows considerable damage after cold ischemia with further damage occurring after reperfusion. The extent of epithelial damage can be quantified by our newly developed bile duct damage score and is a prognostic parameter for biliary complications and graft loss. Possibly, in an intraoperative histological examination, this bile duct damage score may influence decision-making in transplantation surgery.
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Affiliation(s)
- Stefan M Brunner
- Department of Surgery, University Medical Center Regensburg, Regensburg, Germany
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Lattanzi B, Lai Q, Guglielmo N, Giannelli V, Merli M, Giusto M, Melandro F, Ginanni Corradini S, Mennini G, Berloco PB, Rossi M. Graft macrosteatosis and time of T-tube removal as risk factors for biliary strictures after liver transplantation. Clin Transplant 2013; 27:E332-8. [PMID: 23647461 DOI: 10.1111/ctr.12124] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/20/2013] [Indexed: 12/16/2022]
Affiliation(s)
- Barbara Lattanzi
- Gastroenterology Department of Clinical Medicine; Umberto I Hospital; Sapienza University of Rome; Rome; Italy
| | - Quirino Lai
- Department of General Surgery and Organ Transplantation; Umberto I Hospital; Sapienza University of Rome; Rome; Italy
| | - Nicola Guglielmo
- Department of General Surgery and Organ Transplantation; Umberto I Hospital; Sapienza University of Rome; Rome; Italy
| | - Valerio Giannelli
- Gastroenterology Department of Clinical Medicine; Umberto I Hospital; Sapienza University of Rome; Rome; Italy
| | - Manuela Merli
- Gastroenterology Department of Clinical Medicine; Umberto I Hospital; Sapienza University of Rome; Rome; Italy
| | - Michela Giusto
- Gastroenterology Department of Clinical Medicine; Umberto I Hospital; Sapienza University of Rome; Rome; Italy
| | - Fabio Melandro
- Department of General Surgery and Organ Transplantation; Umberto I Hospital; Sapienza University of Rome; Rome; Italy
| | - Stefano Ginanni Corradini
- Gastroenterology Department of Clinical Medicine; Umberto I Hospital; Sapienza University of Rome; Rome; Italy
| | - Gianluca Mennini
- Department of General Surgery and Organ Transplantation; Umberto I Hospital; Sapienza University of Rome; Rome; Italy
| | - Pasquale Bartolomeo Berloco
- Department of General Surgery and Organ Transplantation; Umberto I Hospital; Sapienza University of Rome; Rome; Italy
| | - Massimo Rossi
- Department of General Surgery and Organ Transplantation; Umberto I Hospital; Sapienza University of Rome; Rome; Italy
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Seehofer D, Eurich D, Veltzke-Schlieker W, Neuhaus P. Biliary complications after liver transplantation: old problems and new challenges. Am J Transplant 2013; 13:253-65. [PMID: 23331505 DOI: 10.1111/ajt.12034] [Citation(s) in RCA: 211] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2012] [Revised: 10/01/2012] [Accepted: 10/23/2012] [Indexed: 01/25/2023]
Abstract
Due to a vulnerable blood supply of the bile ducts, biliary complications are a major source of morbidity after liver transplantation (LT). Manifestation is either seen at the anastomotic region or at multiple locations of the donor biliary system, termed as nonanastomotic biliary strictures. Major risk factors include old donor age, marginal grafts and prolonged ischemia time. Moreover, partial LT or living donor liver transplantation (LDLT) and donation after cardiac death (DCD) bear a markedly higher risk of biliary complications. Especially accumulation of several risk factors is critical and should be avoided. Prophylaxis is still a major issue; however no gold standard is established so far, since many risk factors cannot be influenced directly. The diagnostic workup is mostly started with noninvasive imaging studies namely MRI and MRCP, but direct cholangiography still remains the gold standard. Especially nonanastomotic strictures require a multidisciplinary treatment approach. The primary management of anastomotic strictures is mainly interventional. However, surgical revision is finally indicated in a significant number of cases. Using adequate treatment algorithms, a very high success rate can be achieved in anastomotic complications, but in nonanastomotic strictures a relevant number of graft failures are still inevitable.
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Affiliation(s)
- D Seehofer
- Department of General-, Visceral and Transplantation Surgery, Charité Campus Virchow, Berlin, Germany.
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50
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Frongillo F, Grossi U, Avolio AW, Sganga G, Nure E, Pepe G, Bianco G, Lirosi MC, Agnes S. Factors predicting ischemic-type biliary lesions (ITBLs) after liver transplantation. Transplant Proc 2013; 44:2002-4. [PMID: 22974892 DOI: 10.1016/j.transproceed.2012.06.008] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Among biliary complications, ischemic-type biliary lesions (ITBLs) remain a major cause of morbidity in liver transplant recipients, significantly affecting the chance of survival of both patients and grafts. We retrospectively reviewed 10 years of prospectively collected donor and recipient data from April 2001 to April 2011. We evaluated the incidence of ITBL occurrence, exploring the possible predisposing factors, including donor and recipient data. Two hundred fifty-one grafts were harvested: 222 of them were transplanted at our institution, the remaining 29 (11.6%) discarded by our donor team as showing >40% macrovesicular steatosis. Mild-moderate (20%-40%) macrovesicular steatosis (P < .001) and cold ischemia time (P = .048) significantly increased the risk of ITBL, also as an independent risk factor after multivariate analysis.
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Affiliation(s)
- F Frongillo
- Department of General Surgery and Organ Transplantation, Catholic University of the Sacred Heart, Policlinico A. Gemelli, Rome, Italy.
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