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Melgar P, Villodre C, Alcázar C, Franco M, Rubio JJ, Zapater P, Más P, Pascual S, Rodríguez-Laiz GP, Ramia JM. Factors predicting lower hospital stay after liver transplantation using a comprehensive enhanced recovery after surgery (ERAS) protocol. HPB (Oxford) 2025:S1365-182X(25)00076-0. [PMID: 40122765 DOI: 10.1016/j.hpb.2025.03.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2024] [Revised: 02/27/2025] [Accepted: 03/01/2025] [Indexed: 03/25/2025]
Abstract
INTRODUCTION Enhanced recovery after surgery (ERAS) protocols facilitate patient recovery without increasing complication rates. An ERAS protocol designed for our liver transplant (LT) patients obtained a median hospital length of stay (LOS) of 4 days. However, a proportion of patients do not achieve early discharge. This study aimed to identify factors that predict an LOS≤ 4 days. METHODS Identifying factors associated with LOS <4 days in our LT patients. RESULTS We performed 293 LTs (2012-2021), LOS≤4 days in 171 (58.4 %). The following factors emerged as statistically predictors of LOS≤4 days in the univariate analysis: male sex, HCC or HCV patients, lower MELD score, lower BAR score, no DCD patients, shorter operative time, no intraoperative transfusion, shorter ICU stay, no Clavien-Dindo complications grade ≥ III, no primary graft dysfunction, no acute rejection, no readmission at 30 days and no retransplantation were associated to LOS≤4 days. However, in the multivariate analysis, the only independent risk factor that predicted LOS≤4 days was the presence of hepatocarcinoma. DCD donors and higher MELD score were negative factors. CONCLUSIONS Applying ERAS programs in LT patients is beneficial, safe and extensible to all patients, but those with hepatocarcinoma obtain higher rates of LOS≤4 days.
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Affiliation(s)
- Paola Melgar
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Department of Surgery, General University Hospital of Alicante Dr. Balmis, Alicante, Spain; Health and Biomedical Research Institute of Alicante (ISABIAL), Alicante, Spain; University Miguel Hernandez, Alicante, Spain
| | - Celia Villodre
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Department of Surgery, General University Hospital of Alicante Dr. Balmis, Alicante, Spain; Health and Biomedical Research Institute of Alicante (ISABIAL), Alicante, Spain; University Miguel Hernandez, Alicante, Spain
| | - Cándido Alcázar
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Department of Surgery, General University Hospital of Alicante Dr. Balmis, Alicante, Spain; Health and Biomedical Research Institute of Alicante (ISABIAL), Alicante, Spain; University Miguel Hernandez, Alicante, Spain.
| | - Mariano Franco
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Department of Surgery, General University Hospital of Alicante Dr. Balmis, Alicante, Spain; Health and Biomedical Research Institute of Alicante (ISABIAL), Alicante, Spain
| | - Juan J Rubio
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Department of Surgery, General University Hospital of Alicante Dr. Balmis, Alicante, Spain; Health and Biomedical Research Institute of Alicante (ISABIAL), Alicante, Spain
| | - Pedro Zapater
- Health and Biomedical Research Institute of Alicante (ISABIAL), Alicante, Spain; Department of Pharmacy, Unit of Pharmacokinetics and Clinical Pharmacology, General University Hospital of Alicante Dr. Balmis, Spain
| | - Patricio Más
- Health and Biomedical Research Institute of Alicante (ISABIAL), Alicante, Spain; Department of Pharmacy, Unit of Pharmacokinetics and Clinical Pharmacology, General University Hospital of Alicante Dr. Balmis, Spain
| | - Sonia Pascual
- Health and Biomedical Research Institute of Alicante (ISABIAL), Alicante, Spain; Department of Gastroenterology, Hepatology Unit, General University Hospital of Alicante Dr. Balmis, Spain
| | - Gonzalo P Rodríguez-Laiz
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Department of Surgery, General University Hospital of Alicante Dr. Balmis, Alicante, Spain; Health and Biomedical Research Institute of Alicante (ISABIAL), Alicante, Spain
| | - José M Ramia
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Department of Surgery, General University Hospital of Alicante Dr. Balmis, Alicante, Spain; Health and Biomedical Research Institute of Alicante (ISABIAL), Alicante, Spain; University Miguel Hernandez, Alicante, Spain
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Gheorghe G, Diaconu CC, Bungau S, Bacalbasa N, Motas N, Ionescu VA. Biliary and Vascular Complications after Liver Transplantation-From Diagnosis to Treatment. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:850. [PMID: 37241082 PMCID: PMC10221850 DOI: 10.3390/medicina59050850] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/18/2023] [Revised: 04/18/2023] [Accepted: 04/26/2023] [Indexed: 05/28/2023]
Abstract
The last decades have brought impressive advances in liver transplantation. As a result, there was a notable rise in the number of liver transplants globally. Advances in surgical techniques, immunosuppressive therapies and radiologically guided treatments have led to an improvement in the prognosis of these patients. However, the risk of complications remains significant, and the management of liver transplant patients requires multidisciplinary teams. The most frequent and severe complications are biliary and vascular complications. Compared to vascular complications, biliary complications have higher incidence rates but a better prognosis. The early diagnosis and selection of the optimal treatment are crucial to avoid the loss of the graft and even the death of the patient. The development of minimally invasive techniques prevents surgical reinterventions with their associated risks. Liver retransplantation remains the last therapeutic solution for graft dysfunction, one of the main problems, in this case, being the low number of donors.
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Affiliation(s)
- Gina Gheorghe
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila Bucharest, 050474 Bucharest, Romania; (G.G.); (N.B.); (V.-A.I.)
- Gastroenterology Department, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
| | - Camelia Cristina Diaconu
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila Bucharest, 050474 Bucharest, Romania; (G.G.); (N.B.); (V.-A.I.)
- Internal Medicine Department, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
- Department of Visceral Surgery, Center of Excellence in Translational Medicine “Fundeni” Clinical Institute, 022328 Bucharest, Romania
| | - Simona Bungau
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania
| | - Nicolae Bacalbasa
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila Bucharest, 050474 Bucharest, Romania; (G.G.); (N.B.); (V.-A.I.)
- Department of Visceral Surgery, Center of Excellence in Translational Medicine “Fundeni” Clinical Institute, 022328 Bucharest, Romania
| | - Natalia Motas
- Institute of Oncology “Profesor Doctor Alexandru Trestioreanu” Bucharest, 022328 Bucharest, Romania;
- Department of Thoracic Surgery, University of Medicine and Pharmacy Carol Davila Bucharest, 050474 Bucharest, Romania
| | - Vlad-Alexandru Ionescu
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila Bucharest, 050474 Bucharest, Romania; (G.G.); (N.B.); (V.-A.I.)
- Gastroenterology Department, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
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Abstract
Abnormal liver tests are common after liver transplantation. The differential diagnosis depends on the clinical context, particularly the time course, pattern and degree of elevation, and donor and recipient factors. The perioperative period has distinct causes compared with months and years after transplant, including ischemia-reperfusion injury, vascular thrombosis, and primary graft nonfunction. Etiologies seen beyond the perioperative period include biliary complications, rejection, infection, recurrent disease, and non-transplant-specific causes. The evaluation begins with a liver ultrasound with Doppler as well as appropriate laboratory testing and culminates in a liver biopsy if the imaging and laboratory testing is unrevealing.
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Affiliation(s)
- Jacqueline B Henson
- Division of Gastroenterology, Department of Medicine, Duke University, DUMC Box 3913, Durham, NC 27710, USA. https://twitter.com/jackie_henson
| | - Andrew J Muir
- Division of Gastroenterology, Department of Medicine, Duke University, DUMC Box 3913, Durham, NC 27710, USA; Duke Clinical Research Institute, Duke University, DUMC Box 3913, Durham, NC 27710, USA.
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Elkomos BE, Abdelaal A. Do We Need to Use a Stent in Biliary Reconstruction to Decrease the Incidence of Biliary Complications in Liver Transplantation? A Systematic Review and Meta-Analysis. J Gastrointest Surg 2023; 27:180-196. [PMID: 36376727 PMCID: PMC9877101 DOI: 10.1007/s11605-022-05479-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Accepted: 08/20/2022] [Indexed: 11/15/2022]
Abstract
BACKGROUND AND AIM Biliary complications are a significant cause of morbidity post-transplantation, and the routine use of biliary stents in liver transplantation to reduce these complications remains controversial. This study aimed to compare the incidence of biliary complications with and without the use of trans anastomotic biliary stent in liver transplantation. METHOD PubMed, Scopes, Web of Science, and Cochrane library were searched for eligible studies from inception to February 2022, and a systematic review and meta-analysis were done to compare the incidence of biliary complications in the two groups. RESULTS Seventeen studies with a total of 2623 patients were included. The pooled results from the included studies showed an equal rate of biliary complications (i.e., strictures, leaks and cholangitis) in stented and non-stented patients after liver transplantation. However, the cost and biliary intervention rates are higher in stented patients. In addition to that, our sub-group analysis showed no significant decrease in the incidence of biliary complications after using trans anastomotic biliary stent in living donor liver transplant (LDLT), deceased donor liver transplant (DDLT), Roux-en-Y hepaticojejunostomy (RYHJ), and duct-to-duct anastomosis, pediatric, and adult liver transplantation. CONCLUSION No added benefit on the routine use of endobiliary stent in liver transplantation. However, stented patients are at higher risk of needing multiple ERCPs.
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Affiliation(s)
| | - Amr Abdelaal
- General Surgery Department, Ain Shams University Hospital, Cairo, Egypt
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5
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Meier RPH, Kelly Y, Yamaguchi S, Braun HJ, Lunow-Luke T, Adelmann D, Niemann C, Maluf DG, Dietch ZC, Stock PG, Kang SM, Feng S, Posselt AM, Gardner JM, Syed SM, Hirose R, Freise CE, Ascher NL, Roberts JP, Roll GR. Advantages and Limitations of Clinical Scores for Donation After Circulatory Death Liver Transplantation. Front Surg 2022; 8:808733. [PMID: 35071316 PMCID: PMC8766343 DOI: 10.3389/fsurg.2021.808733] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Accepted: 12/09/2021] [Indexed: 11/17/2022] Open
Abstract
Background: Scoring systems have been proposed to select donation after circulatory death (DCD) donors and recipients for liver transplantation (LT). We hypothesized that complex scoring systems derived in large datasets might not predict outcomes locally. Methods: Based on 1-year DCD-LT graft survival predictors in multivariate logistic regression models, we designed, validated, and compared a simple index using the University of California, San Francisco (UCSF) cohort (n = 136) and a universal-comprehensive (UC)-DCD score using the United Network for Organ Sharing (UNOS) cohort (n = 5,792) to previously published DCD scoring systems. Results: The total warm ischemia time (WIT)-index included donor WIT (dWIT) and hepatectomy time (dHep). The UC-DCD score included dWIT, dHep, recipient on mechanical ventilation, transjugular-intrahepatic-portosystemic-shunt, cause of liver disease, model for end-stage liver disease, body mass index, donor/recipient age, and cold ischemia time. In the UNOS cohort, the UC-score outperformed all previously published scores in predicting DCD-LT graft survival (AUC: 0.635 vs. ≤0.562). In the UCSF cohort, the total WIT index successfully stratified survival and biliary complications, whereas other scores did not. Conclusion: DCD risk scores generated in large cohorts provide general guidance for safe recipient/donor selection, but they must be tailored based on non-/partially-modifiable local circumstances to expand DCD utilization.
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Affiliation(s)
- Raphael P. H. Meier
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
- Department of Surgery, University of Maryland, Baltimore, MD, United States
| | - Yvonne Kelly
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Seiji Yamaguchi
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Hillary J. Braun
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Tyler Lunow-Luke
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Dieter Adelmann
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
- Department of Anesthesia, University of California, San Francisco, San Francisco, CA, United States
| | - Claus Niemann
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
- Department of Anesthesia, University of California, San Francisco, San Francisco, CA, United States
| | - Daniel G. Maluf
- Department of Surgery, University of Maryland, Baltimore, MD, United States
| | - Zachary C. Dietch
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Peter G. Stock
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Sang-Mo Kang
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Sandy Feng
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Andrew M. Posselt
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - James M. Gardner
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Shareef M. Syed
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Ryutaro Hirose
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Chris E. Freise
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Nancy L. Ascher
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - John P. Roberts
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Garrett R. Roll
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
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6
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Honarmand K, Alshamsi F, Foroutan F, Rochwerg B, Belley-Cote E, Mclure G, D'Aragon F, Ball IM, Sener A, Selzner M, Guyatt G, Meade MO. Antemortem Heparin in Organ Donation After Circulatory Death Determination: A Systematic Review of the Literature. Transplantation 2021; 105:e337-e346. [PMID: 33901108 DOI: 10.1097/tp.0000000000003793] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Donation after circulatory death determination frequently involves antemortem heparin administration to mitigate peri-arrest microvascular thrombosis. We systematically reviewed the literature to: (1) describe heparin administration practices and (2) explore the effects on transplant outcomes. We searched MEDLINE and EMBASE for studies reporting donation after circulatory death determination heparin practices including use, dosage, and timing (objective 1). To explore associations between antemortem heparin and transplant outcomes (objective 2), we (1) summarized within-study comparisons and (2) used meta-regression analyses to examine associations between proportions of donors that received heparin and transplant outcomes. We assessed risk of bias using the Newcastle Ottawa Scale and applied the GRADE methodology to determine certainty in the evidence. For objective 1, among 55 eligible studies, 48 reported heparin administration to at least some donors (range: 15.8%-100%) at variable doses (up to 1000 units/kg) and times relative to withdrawal of life-sustaining therapy. For objective 2, 7 studies that directly compared liver transplants with and without antemortem heparin reported lower rates of primary nonfunction, hepatic artery thrombosis, graft failure at 5 y, or recipient mortality (low certainty of evidence). In contrast, meta-regression analysis of 32 liver transplant studies detected no associations between the proportion of donors that received heparin and rates of early allograft dysfunction, primary nonfunction, hepatic artery thrombosis, biliary ischemia, graft failure, retransplantation, or patient survival (very low certainty of evidence). In conclusion, antemortem heparin practices vary substantially with an uncertain effect on transplant outcomes. Given the controversies surrounding antemortem heparin, clinical trials may be warranted.
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Affiliation(s)
- Kimia Honarmand
- Division of Critical Care, Department of Medicine, Western University, London, ON, Canada
| | - Fayez Alshamsi
- Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Farid Foroutan
- Ted Rogers Centre for Heart Research, Peter Munk Cardiac Center, University Health Network, Toronto, ON, Canada
| | - Bram Rochwerg
- Division of Critical Care, Department of Medicine, McMaster University, Hamilton, ON, Canada
- Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, ON, Canada
| | - Emilie Belley-Cote
- Division of Critical Care, Department of Medicine, McMaster University, Hamilton, ON, Canada
- Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, ON, Canada
- Division of Cardiology, Department of Medicine, McMaster University, Hamilton, Canada
- Population Health Research Institute, Hamilton, ON, Canada
| | - Graham Mclure
- Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, ON, Canada
| | - Frederick D'Aragon
- Department of Anesthesiology, Université de Sherbrooke, Sherbrooke, QC, Canada
| | - Ian M Ball
- Division of Critical Care, Department of Medicine, Western University, London, ON, Canada
- Department of Epidemiology and Biostatistics, Western University, London, ON, Canada
| | - Alp Sener
- Department of Surgery and Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
| | - Markus Selzner
- Multi-Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, ON, Canada
| | - Gordon Guyatt
- Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, ON, Canada
- Department of Medicine, McMaster University, Hamilton, ON, Canada
| | - Maureen O Meade
- Division of Critical Care, Department of Medicine, McMaster University, Hamilton, ON, Canada
- Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, ON, Canada
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Kose A, Altunisik Toplu S, Akbulut S, Yasar S, Sarici KB, Duman Y, Kutlu R, Isik B, Colak YZ, Yilmaz S, Bayindir Y. Evaluation of clinical characteristics and outcomes of postoperative ınfections in living liver donors. Int J Clin Pract 2021; 75:e14324. [PMID: 33960083 DOI: 10.1111/ijcp.14324] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Accepted: 05/03/2021] [Indexed: 02/05/2023] Open
Abstract
AIM To analyze developing infections after living donor hepatectomy (LDH) in living liver donors (LLDs). METHODS Demographic and clinical characteristics of 1106 LLDs were retrospectively analyzed in terms of whether postoperative infection development. Therefore, LLDs were divided into two groups: with (n = 190) and without (n = 916) antimicrobial agent use. RESULTS The median age was 29.5 (min-max: 18-55). A total of 257 (23.2%) infection attacks (min-max: 1-8) was developed in 190 (17.2%) LLDs. The patients with the infection that were longer intensive care unit (ICU) and hospital stays, higher hospital admissions, emergency transplantation, invasive procedures for ERCP, PTC biloma, and abscess drainage, and the presence of relaparatomies and transcystic catheters. Infection attacks are derived from a 58.3% hepatobiliary system, 13.2% urinary system, 6.6% surgical site, and 5.8% respiratory system. The most common onset symptoms were fever, abdominal pain, nausea, and vomiting. A total of 125 positive results was detected from 77 patients with culture positivity. The most detected microorganisms from the cultures taken are Extended-Spectrum β-lactamases (ESBL) producing Klebsiella pneumonia (16.8%) and Escherichia coli (16%), Methicillin-Resistant Staphylococcus aureus [(MRSA) (9.6%)], Methicillin-susceptible S aureus [(MSSA) (9.6%)], and Pseudomonas aeruginosa (8.8%), respectively. The average number of ICU hospitalization days was 3 ± 2 (min 1-max 30, IQR:1) and hospitalization days was 14 ± 12 (min 3-max 138, IQR: 8). All infection attacks were successfully treated. No patients died because of infection or another surgical complication. CONCLUSION Infections commonly observed infected biloma, cholangitis, and abscess arising from the biliary system and other nosocomial infections are the feared complications in LLDs. These infections should be managed multidisciplinary without delay and carefully.
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Affiliation(s)
- Adem Kose
- Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Inonu University, Malatya, Turkey
| | - Sibel Altunisik Toplu
- Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Inonu University, Malatya, Turkey
| | - Sami Akbulut
- Department of Liver Transplantation Institute, Faculty of Medicine, Inonu University, Malatya, Turkey
| | - Seyma Yasar
- Department of Biostatistics, and Medical Informatics, Faculty of Medicine, Inonu University, Malatya, Turkey
| | - Kemal Baris Sarici
- Department of Liver Transplantation Institute, Faculty of Medicine, Inonu University, Malatya, Turkey
| | - Yucel Duman
- Department of Medical Microbiology, Faculty of Medicine, Inonu University, Malatya, Turkey
| | - Ramazan Kutlu
- Department of Radiology, Faculty of Medicine, Inonu University, Malatya, Turkey
| | - Burak Isik
- Department of Liver Transplantation Institute, Faculty of Medicine, Inonu University, Malatya, Turkey
| | - Yusuf Ziya Colak
- Department of Anesthesiology, Faculty of Medicine, Inonu University, Malatya, Turkey
| | - Sezai Yilmaz
- Department of Liver Transplantation Institute, Faculty of Medicine, Inonu University, Malatya, Turkey
| | - Yasar Bayindir
- Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Inonu University, Malatya, Turkey
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Zhang X, Du P, Luo K, Li Y, Liu Z, Wang W, Zeng C, Ye Q, Xiao Q. Hypoxia-inducible factor-1alpha protects the liver against ischemia-reperfusion injury by regulating the A2B adenosine receptor. Bioengineered 2021; 12:3737-3752. [PMID: 34288817 PMCID: PMC8806673 DOI: 10.1080/21655979.2021.1953217] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Hepatic ischemia-reperfusion injury (IRI) is an inevitable complication associated with liver surgical procedures, and its pathological process remains elusive. Therefore, the present study investigated the role and mechanism of hypoxia-inducible factor-1alpha (HIF-1α) in hepatic IRI. Here, we constructed rat models with hepatic IRI and BRL-3A cell models with hypoxia/reoxygenation (H/R) insult. The extent of liver injury was assayed by measuring serum ALT/AST levels and performing H&E staining; the levels of SOD, MDA, MPO, IL-6 and TNF-α were determined using commercial kits; apoptosis was detected using the TUNEL assay and flow cytometry; and the expression of HIF-1α/A2BAR signaling-related molecules and apoptosis-associated indicators was detected using Western blotting or qRT-PCR. The expression level of HIF-1α was significantly upregulated in the liver of rats subjected to IRI, as well as in BRL-3A cells treated with H/R. HIF-1α overexpression exerted a protective effect on hepatic IRI or H/R insult by reducing serum aminotransferase levels and hepatic necrosis, inhibiting inflammation and apoptosis of hepatocytes, and alleviating oxidative stress. In contrast, inhibition of HIF-1α expression exacerbated hepatic injury induced by IR or H/R. Mechanistically, the expression level of A2BAR was markedly increased during hepatic IRI or H/R insult. Moreover, A2BAR expression increased with HIF-1α upregulation and decreased with HIF-1α downregulation. Importantly, inhibition of A2BAR signaling abolished HIF-1α overexpression-mediated hepatoprotection. Taken together, HIF-1α exerts protective effects on hepatic IRI by attenuating liver necrosis, the inflammatory response, oxidative stress and apoptosis, and its mechanism may be related to the upregulation of A2BAR signaling.
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Affiliation(s)
- Xingjian Zhang
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Peng Du
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Kaifeng Luo
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Yong Li
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Zhongzhong Liu
- Institute of Hepatobiliary Diseases, Transplant Center, Hubei Key Laboratory of Medical Technology on Transplantation, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China
| | - Wei Wang
- Institute of Hepatobiliary Diseases, Transplant Center, Hubei Key Laboratory of Medical Technology on Transplantation, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China
| | - Cheng Zeng
- Institute of Hepatobiliary Diseases, Transplant Center, Hubei Key Laboratory of Medical Technology on Transplantation, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China
| | - Qifa Ye
- Institute of Hepatobiliary Diseases, Transplant Center, Hubei Key Laboratory of Medical Technology on Transplantation, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China
| | - Qi Xiao
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
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9
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Barbaro F, Tringali A, Larghi A, Baldan A, Onder G, Familiari P, Boškoski I, Perri V, Costamagna G. Endoscopic management of non-anastomotic biliary strictures following liver transplantation: Long-term results from a single-center experience. Dig Endosc 2021; 33:849-857. [PMID: 33080081 DOI: 10.1111/den.13879] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Revised: 10/11/2020] [Accepted: 10/16/2020] [Indexed: 12/13/2022]
Abstract
OBJECTIVES Studies on endoscopic treatment of non-anastomotic biliary strictures (NABS) following orthotopic liver transplantation (OLT) are scanty and with a short follow-up. The long-term results of endoscopic treatment with plastic stents of NABS following OLT were analyzed. METHODS Retrospective analysis of consecutive enrolled patients who underwent endoscopic treatment for NABS after OLT between 1997 and 2015. Endoscopic treatment success was defined as stricture resolution, without recurrence. RESULTS During the study period, 33 patients with NABS underwent endoscopic retrograde cholangiopancreatography (ERCP) in our center. A total of 68 ERCP were performed with a 4.4% of procedure-related adverse events. Mortality related to cholangitis secondary to endoscopic procedures was 12%. After median follow-up of 70.3 months from stents removal, NABS resolution was obtained in 12 out of 24 (50%) patients. Only one case of late NABS recurrence was observed which was successfully retreated endoscopically. According to our data analysis NABS occurring <12 months from OLT showed a worse prognosis (P < 0.04). CONCLUSIONS The follow-up of this study confirms that endoscopic treatment of NABS is unsatisfactory. However, patients who respond to endoscopic treatment maintain the response over time. Prompt treatment of acute cholangitis due to stents occlusion is advised in these patients to avoid high mortality rates.
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Affiliation(s)
- Federico Barbaro
- Digestive Endoscopy Unit, Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.,Centre for Endoscopic Research Therapeutics and Training (CERTT), Università Cattolica del Sacro Cuore, Rome, Italy
| | - Andrea Tringali
- Digestive Endoscopy Unit, Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.,Centre for Endoscopic Research Therapeutics and Training (CERTT), Università Cattolica del Sacro Cuore, Rome, Italy
| | - Alberto Larghi
- Digestive Endoscopy Unit, Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.,Centre for Endoscopic Research Therapeutics and Training (CERTT), Università Cattolica del Sacro Cuore, Rome, Italy
| | - Anna Baldan
- Gastroenterology and Transplant Hepatology, Ospedale Papa Giovanni XXIII, Bergamo, Italy
| | - Graziano Onder
- Department of Geriatrics, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Pietro Familiari
- Digestive Endoscopy Unit, Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.,Centre for Endoscopic Research Therapeutics and Training (CERTT), Università Cattolica del Sacro Cuore, Rome, Italy
| | - Ivo Boškoski
- Digestive Endoscopy Unit, Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.,Centre for Endoscopic Research Therapeutics and Training (CERTT), Università Cattolica del Sacro Cuore, Rome, Italy
| | - Vincenzo Perri
- Digestive Endoscopy Unit, Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.,Centre for Endoscopic Research Therapeutics and Training (CERTT), Università Cattolica del Sacro Cuore, Rome, Italy
| | - Guido Costamagna
- Digestive Endoscopy Unit, Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.,Centre for Endoscopic Research Therapeutics and Training (CERTT), Università Cattolica del Sacro Cuore, Rome, Italy
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10
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Haque O, Raigani S, Rosales I, Carroll C, Coe TM, Baptista S, Yeh H, Uygun K, Delmonico FL, Markmann JF. Thrombolytic Therapy During ex-vivo Normothermic Machine Perfusion of Human Livers Reduces Peribiliary Vascular Plexus Injury. Front Surg 2021; 8:644859. [PMID: 34222314 PMCID: PMC8245781 DOI: 10.3389/fsurg.2021.644859] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 05/24/2021] [Indexed: 12/29/2022] Open
Abstract
Background: A major limitation in expanding the use of donation after circulatory death (DCD) livers in transplantation is the increased risk of graft failure secondary to ischemic cholangiopathy. Warm ischemia causes thrombosis and injury to the peribiliary vascular plexus (PVP), which is supplied by branches of the hepatic artery, causing higher rates of biliary complications in DCD allografts. Aims/Objectives: We aimed to recondition discarded DCD livers with tissue plasminogen activator (tPA) while on normothermic machine perfusion (NMP) to improve PVP blood flow and reduce biliary injury. Methods: Five discarded DCD human livers underwent 12 h of NMP. Plasminogen was circulated in the base perfusate prior to initiation of perfusion and 1 mg/kg of tPA was administered through the hepatic artery at T = 0.5 h. Two livers were split prior to perfusion (S1, S2), with tPA administered in one lobe, while the other served as a control. The remaining three whole livers (W1-W3) were compared to seven DCD control liver perfusions (C1-C7) with similar hepatocellular and biliary viability criteria. D-dimer levels were measured at T = 1 h to verify efficacy of tPA. Lactate, total bile production, bile pH, and difference in biliary injury scores before and after perfusion were compared between tPA and non-tPA groups using unpaired, Mann-Whitney tests. Results: Average weight-adjusted D-dimer levels were higher in tPA livers in the split and whole-liver model, verifying drug function. There were no differences in perfusion hepatic artery resistance, portal vein resistance, and arterial lactate between tPA livers and non-tPA livers in both the split and whole-liver model. However, when comparing biliary injury between hepatocellular and biliary non-viable whole livers, tPA livers had significantly lower PVP injury scores (0.67 vs. 2.0) and mural stroma (MS) injury scores (1.3 vs. 2.7). Conclusion: This study demonstrates that administration of tPA into DCD livers during NMP can reduce PVP and MS injury. Further studies are necessary to assess the effect of tPA administration on long term biliary complications.
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Affiliation(s)
- Omar Haque
- Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, United States.,Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, United States.,Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA, United States.,Shriners Hospitals for Children, Boston, MA, United States.,Harvard Medical School, Boston, MA, United States
| | - Siavash Raigani
- Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, United States.,Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA, United States.,Shriners Hospitals for Children, Boston, MA, United States.,Harvard Medical School, Boston, MA, United States
| | - Ivy Rosales
- Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, United States.,Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA, United States.,Harvard Medical School, Boston, MA, United States
| | - Cailah Carroll
- Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, United States.,Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA, United States.,Shriners Hospitals for Children, Boston, MA, United States
| | - Taylor M Coe
- Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, United States.,Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA, United States.,Shriners Hospitals for Children, Boston, MA, United States.,Harvard Medical School, Boston, MA, United States
| | - Sofia Baptista
- Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA, United States.,Shriners Hospitals for Children, Boston, MA, United States
| | - Heidi Yeh
- Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, United States.,Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA, United States.,Harvard Medical School, Boston, MA, United States
| | - Korkut Uygun
- Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, United States.,Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA, United States.,Shriners Hospitals for Children, Boston, MA, United States.,Harvard Medical School, Boston, MA, United States
| | - Francis L Delmonico
- Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, United States.,Harvard Medical School, Boston, MA, United States.,New England Donor Services (NEDS), Waltham, MA, United States
| | - James F Markmann
- Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, United States.,Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA, United States.,Harvard Medical School, Boston, MA, United States
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11
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Percutaneous Transhepatic Single-Operator Cholangioscopy-Guided Intraductal Stone Therapy in a Liver Transplant Patient With Ischemic Cholangiopathy. ACG Case Rep J 2021; 8:e00595. [PMID: 34109253 PMCID: PMC8177873 DOI: 10.14309/crj.0000000000000595] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Accepted: 02/16/2021] [Indexed: 12/17/2022] Open
Abstract
Ischemic cholangiopathy is a feared complication after liver transplantation. We present a 68-year-old man who is status postorthotopic liver transplant from a donation after cardiac death. His posttransplant course was complicated by the development of a biliary anastomotic stricture, ischemic cholangiopathy, biloma, recurrent cholangitis, and intrahepatic stones. Through the use of antegrade cholangioscopy with a single-operator cholangioscope (SpyGlass 2; Boston Scientific, Boston, MA) passed through a percutaneous sheath, we were able to visualize impacted stones within the left intrahepatic system and treat them using electrohydraulic lithotripsy for stone fragmentation and removal.
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12
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Boeva I, Karagyozov PI, Tishkov I. Post-liver transplant biliary complications: Current knowledge and therapeutic advances. World J Hepatol 2021; 13:66-79. [PMID: 33584987 PMCID: PMC7856868 DOI: 10.4254/wjh.v13.i1.66] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2020] [Revised: 11/01/2020] [Accepted: 12/02/2020] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation is the current standard of care for end-stage liver disease and an accepted therapeutic option for acute liver failure and primary liver tumors. Despite the remarkable advances in the surgical techniques and immunosuppressive therapy, the postoperative morbidity and mortality still remain high and the leading causes are biliary complications, which affect up to one quarter of recipients. The most common biliary complications are anastomotic and non-anastomotic biliary strictures, leaks, bile duct stones, sludge and casts. Despite the absence of a recommended treatment algorithm many options are available, such as surgery, percutaneous techniques and interventional endoscopy. In the last few years, endoscopic techniques have widely replaced the more aggressive percutaneous and surgical approaches. Endoscopic retrograde cholangiography is the preferred technique when duct-to-duct anastomosis has been performed. Recently, new devices and techniques have been developed and this has led to a remarkable increase in the success rate of minimally invasive procedures. Understanding the mechanisms of biliary complications helps in their early recognition which is the prerequisite for successful treatment. Aggressive endoscopic therapy is essential for the reduction of morbidity and mortality in these cases. This article focuses on the common post-transplant biliary complications and the available interventional treatment modalities.
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Affiliation(s)
- Irina Boeva
- Department of Interventional Gastroenterology, Acibadem City Clinic Tokuda Hospital, Sofia 1407, Bulgaria
| | - Petko Ivanov Karagyozov
- Department of Interventional Gastroenterology, Clinic of Gastroenterology, Acibadem City Clinic Tokuda Hospital, Sofia 1407, Bulgaria.
| | - Ivan Tishkov
- Department of Interventional Gastroenterology, Acibadem City Clinic Tokuda Hospital, Sofia 1407, Bulgaria
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13
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Agmatine Attenuates Liver Ischemia Reperfusion Injury by Activating Wnt/β-catenin Signaling in Mice. Transplantation 2020; 104:1906-1916. [PMID: 32032294 DOI: 10.1097/tp.0000000000003161] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
BACKGROUND Liver ischemia reperfusion injury (LIRI) is a common problem during surgical procedures of the liver. It causes severe inflammatory responses and cell death, eventually leading to serious liver damage. Agmatine (AGM) is an endogenous polyamine with analgesic, anti-inflammatory, and antiapoptotic effects. However, it is still unknown whether AGM can protect the liver from damage caused by LIRI. METHODS For the in vivo experiments, a mouse model of partial warm hepatic ischemia reperfusion was established using C57BL/6J mice and then serum transaminase concentrations were analyzed. Histopathology was used to evaluate the degree of liver injury and quantitative real-time PCR was used to measure the amount of inflammatory cytokines. For the in vitro experiments, a cellular model of cobalt chloride (CoCl2)-induced hypoxia was established using AML12 cells. Flow cytometry was performed to measure the apoptosis levels. Western blotting analysis was conducted to measure the levels of proteins involved in apoptosis and Wnt/β-catenin signaling. We also chose 2 inhibitors of the Wnt/β-catenin signaling to elucidate the relationship between AGM and the Wnt/β-catenin signaling. RESULTS AGM showed protective effects against LIRI-induced liver damage, inflammatory responses, and cell apoptosis along with alleviation of CoCl2-induced hepatocyte injury. AGM activated the Wnt/β-catenin signaling pathway during LIRI and CoCl2-induced hepatocyte injury; however, when the Wnt/β-catenin pathway was inhibited, the protective effects of AGM declined. CONCLUSIONS AGM showed protective effects against LIRI by activating the Wnt/β-catenin signaling pathway.
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14
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Abstract
INTRODUCTION Liver transplantation is a life-changing event for patients and survival following transplantation has improved significantly since the first transplantation in 1967. Following liver transplantation, patients face a unique set of healthcare management decisions including transplantation-specific complications, recurrence of primary liver disease, as well as metabolic and malignancy concerns related to immunosuppression. As more patients with liver disease receive transplantation and live longer, understanding and managing these patients will require not only transplant specialist but also local subspecialist and primary care physicians. AREAS COVERED This review covers common issues related to the management of patients following liver transplantation including immunosuppression, liver allograft dysfunction, metabolic complications, as well as routine health maintenance such as immunizations and cancer screening. EXPERT OPINION Optimizing medical care for patients following liver transplant will benefit from ensuring all providers, not just transplant specialist, have a basic understanding of the common issues encountered in the post-transplant patient. This review provides an overview of common healthcare concerns and management options for patients following liver transplantation.
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Affiliation(s)
- Nicholas Hoppmann
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham , Birmingham, Alabama, USA
| | - Omar Massoud
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham , Birmingham, Alabama, USA
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15
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Czigany Z, Craigie EC, Lurje G, Song S, Yonezawa K, Yamamoto Y, Minor T, Tolba RH. Adenosine A2a Receptor Stimulation Attenuates Ischemia-Reperfusion Injury and Improves Survival in A Porcine Model of DCD Liver Transplantation. Int J Mol Sci 2020; 21:E6747. [PMID: 32938013 PMCID: PMC7555737 DOI: 10.3390/ijms21186747] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2020] [Revised: 09/08/2020] [Accepted: 09/11/2020] [Indexed: 12/14/2022] Open
Abstract
Orthotopic liver transplantation (OLT) using allografts from donation after circulatory death (DCD) is potentially associated with compromised clinical outcomes due to ischemia-reperfusion injury (IRI)-induced organ damage and graft-related complications. The aim of this study was to provide in vivo data on the effects of adenosine A2a receptor stimulation in a clinically relevant large animal model of DCD liver transplantation. Cardiac arrest was induced in German Landrace pigs (n = 10; 20-25 kg). After 30 min of warm ischemia, the donor liver was retrieved following a cold flush with 3 L of histidine-tryptophan-ketoglutarate-HTK solution. Animals of the treatment group (n = 5/group) received a standard dose of the selective adenosine receptor agonist CGS 21680 added to the cold flush. All grafts were stored for 4.5 h at 4 °C in HTK-solution before OLT. Hepatocellular injury, apoptosis, protein kinase A-PKA activity, graft microcirculation, liver function, and animal survival were assessed. Compared to untreated livers, adenosine A2a receptor stimulation resulted in improved tissue microcirculation (103% ± 5% vs. 38% ± 4% compared to baseline; p < 0.05), accelerated functional recovery of the graft (indocyanine green-plasma disappearance rate (ICG-PDR) of 75% ± 18% vs. 40% ± 30% after 3 h), increased PKA activity ratio (56% ± 3% vs. 32% ± 3%; p < 0.001 after 1 h), and consequently reduced tissue necrosis and apoptosis. The potent protective effects were clinically manifested in significantly improved survival in the treatment group after 72 h (100% vs. 40%; p = 0.04). The ex vivo administration of adenosine A2a receptor agonist during the back-table flush mitigates IRI-mediated tissue damage and improves functional graft recovery and survival in a large animal model of DCD liver transplantation.
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Affiliation(s)
- Zoltan Czigany
- Department of Surgery and Transplantation, Faculty of Medicine, University Hospital RWTH Aachen, 52074 Aachen, Germany;
- Institute for Laboratory Animal Science and Experimental Surgery, Faculty of Medicine, RWTH-Aachen University, 52074 Aachen, Germany;
| | - Eve Christiana Craigie
- Institute for Laboratory Animal Science and Experimental Surgery, Faculty of Medicine, RWTH-Aachen University, 52074 Aachen, Germany;
| | - Georg Lurje
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum–Charité-Universitätsmedizin, 13353 Berlin, Germany;
| | - Shaowei Song
- Department of Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110122, China;
| | - Kei Yonezawa
- Department of Surgery, Shizuoka City Hospital, Shizuoka 420-8527, Japan;
| | - Yuzo Yamamoto
- Department of Gastroenterological Surgery, Akita University Graduate School of Medicine, Akita 010-0825, Japan;
| | - Thomas Minor
- Department of General, Visceral, and Transplantation Surgery, University Hospital Essen, 45147 Essen, Germany;
| | - René Hany Tolba
- Institute for Laboratory Animal Science and Experimental Surgery, Faculty of Medicine, RWTH-Aachen University, 52074 Aachen, Germany;
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16
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Hashimoto K. Liver graft from donation after circulatory death donor: Real practice to improve graft viability. Clin Mol Hepatol 2020; 26:401-410. [PMID: 32646199 PMCID: PMC7641554 DOI: 10.3350/cmh.2020.0072] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Accepted: 05/27/2020] [Indexed: 12/14/2022] Open
Abstract
Donation after circulatory death (DCD) is an increasing source of liver grafts for transplantation, yet outcomes have been inferior compared to donation after brain death liver transplantation. These worse outcomes are mainly due to the severe graft injury resulting from mandatory warm ischemia during DCD organ recovery. New evidence, however, indicates that improved donor selection and surgical techniques can decrease the risk of graft failure and ischemic cholangiopathy (IC). Under current best practices, DCD organs are retrieved with the super-rapid technique, optimizing timing and protecting the liver graft from detrimental warm ischemia. Graft viability is influenced by both the quantity and quality of warm ischemia, which is unique to each donor and causes various degrees of pathophysiologic consequences. Evidence also shows that the choice of preservation solution and premortem heparin administration influences graft viability. Additionally, although the precise mechanism of IC remains unknown, stasis of blood during donor warm ischemia may cause the formation of microthrombi in the peribiliary vascular plexus and ischemia of the bile duct. Importantly, thrombolytic protocols show a possible preventive modality for IC. Finally, while ex vivo machine perfusion technology has gained an interest in DCD liver transplantation, further studies are necessary to evaluate the effectiveness of this evolving field to improve graft quality and transplant outcomes.
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Affiliation(s)
- Koji Hashimoto
- Department of General Surgery, Digestive Disease & Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
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17
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Lim M, Rhu J, Kim S, Lee S, Kim JM, Choi GS, Joh JW. Early reoperation after adult living-donor liver transplantation is associated with poor survival. KOREAN JOURNAL OF TRANSPLANTATION 2019; 33:128-134. [PMID: 35769981 PMCID: PMC9188941 DOI: 10.4285/jkstn.2019.33.4.128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Revised: 12/06/2019] [Accepted: 12/19/2019] [Indexed: 11/04/2022] Open
Abstract
Background Patients who undergo reoperation after living-donor liver transplantation (LDLT) have poor outcomes. However, the specific outcomes of patients undergoing reoperation due to gastrointestinal (GI) tract-related complications following adult LDLT are relatively unknown. In the present study, we investigated the relationship between the causes and outcomes of reoperation after LDLT and classified the risk groups. Methods We performed a retrospective analysis of 506 patients who underwent LDLT at Samsung Medical Center in Seoul between 2010 and 2016. Results Among 506 adult LDLT recipients, 98 (19.4%) underwent reoperation. The causes for reoperation included bleeding (n=39, 39.8%), vascular complications (n=26, 26.5%), wound complications (n=12, 12.2%), bile leakage (n=7, 7.1%), GI tract complications (n=6, 6.1%), and others (n=8, 8.1%). Based on a multivariate analysis, we identified prolonged operation time, hospitalization days, and a history of previous hepatocellular carcinoma-related operation as independent risk factors for reoperation. Patient survival after 3 months, 1 year, 3 years, and 5 years was 96.3%, 90.6%, 82.5%, and 79.4% in the non-reoperation group and 95.9%, 82.7%, 72.8% and 69.3% in the reoperation group, respectively. Patient survival in the reoperation group was significantly lower than that in the non-reoperation group (P=0.018). In the reoperation group, the survival rates of patients with GI tract-related complications—including bile leakage and GI tract complications—were significantly worse than those of patients with non-GI tract-related complications such as bleeding, vascular complications, and wound complications (P<0.001). Conclusions Our results showed that patient outcomes are poor after early reoperation after LDLT and that patients with GI tract-related complications have a higher risk of mortality.
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Affiliation(s)
- Manuel Lim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jinsoo Rhu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sangjin Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seohee Lee
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Gyu-Seong Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jae-Won Joh
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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18
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Hessheimer AJ, Riquelme F, Fundora-Suárez Y, García Pérez R, Fondevila C. Normothermic perfusion and outcomes after liver transplantation. Transplant Rev (Orlando) 2019; 33:200-208. [PMID: 31239189 DOI: 10.1016/j.trre.2019.06.001] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Revised: 06/04/2019] [Accepted: 06/09/2019] [Indexed: 01/04/2023]
Abstract
Ischemia has been a persistent and largely unavoidable element in solid organ transplantation, contributing to graft deterioration and adverse post-transplant outcomes. In liver transplantation, where available organs arise with greater frequency from marginal donors (i.e., ones that are older, obese, and/or declared dead following cardiac arrest through the donation after circulatory death process), there is increasing interest using dynamic perfusion strategies to limit, assess, and even reverse the adverse effects of ischemia in these grafts. Normothermic perfusion, in particular, is used to restore the flow of oxygen and other metabolic substrates at physiological temperatures. It may be used in liver transplantation both in situ following cardiac arrest in donation after circulatory death donors or during part or all of the ex situ preservation phase. This review article addresses issues relevant to use of normothermic perfusion strategies in liver transplantation, including technical and logistical aspects associated with establishing and maintaining normothermic perfusion in its different forms and clinical outcomes that have been reported to date.
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Affiliation(s)
- Amelia J Hessheimer
- Hepatopancreatobiliary Surgery & Transplantation, General & Digestive Surgery Service, Digestive & Metabolic Disease Institute (ICMDM), Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, Spain.
| | - Francisco Riquelme
- Hepatopancreatobiliary Surgery & Transplantation, General & Digestive Surgery Service, Digestive & Metabolic Disease Institute (ICMDM), Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, Spain
| | - Yiliam Fundora-Suárez
- Hepatopancreatobiliary Surgery & Transplantation, General & Digestive Surgery Service, Digestive & Metabolic Disease Institute (ICMDM), Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, Spain
| | - Rocío García Pérez
- Hepatopancreatobiliary Surgery & Transplantation, General & Digestive Surgery Service, Digestive & Metabolic Disease Institute (ICMDM), Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, Spain
| | - Constantino Fondevila
- Hepatopancreatobiliary Surgery & Transplantation, General & Digestive Surgery Service, Digestive & Metabolic Disease Institute (ICMDM), Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, Spain
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19
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Gans JH, Lipman J, Golowa Y, Kinkhabwala M, Kaubisch A. Hepatic Cancers Overview: Surgical and Chemotherapeutic Options, How Do Y-90 Microspheres Fit in? Semin Nucl Med 2019; 49:170-181. [DOI: 10.1053/j.semnuclmed.2019.01.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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20
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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: 16] [Impact Index Per Article: 2.7] [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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21
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Moy BT, Birk JW. A Review on the Management of Biliary Complications after Orthotopic Liver Transplantation. J Clin Transl Hepatol 2019; 7:61-71. [PMID: 30944822 PMCID: PMC6441650 DOI: 10.14218/jcth.2018.00028] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2018] [Revised: 09/23/2018] [Accepted: 10/29/2018] [Indexed: 02/07/2023] Open
Abstract
Orthotopic liver transplantation is the definitive treatment for end-stage liver disease and hepatocellular carcinomas. Biliary complications are the most common complications seen after transplantation, with an incidence of 10-25%. These complications are seen both in deceased donor liver transplant and living donor liver transplant. Endoscopic treatment of biliary complications with endoscopic retrograde cholangiopancreatography (commonly known as ERCP) has become a mainstay in the management post-transplantation. The success rate has reached 80% in an experienced endoscopist's hands. If unsuccessful with ERCP, percutaneous transhepatic cholangiography can be an alternative therapy. Early recognition and treatment has been shown to improve morbidity and mortality in post-liver transplant patients. The focus of this review will be a learned discussion on the types, diagnosis, and treatment of biliary complications post-orthotopic liver transplantation.
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Affiliation(s)
- Brian T. Moy
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, USA
| | - John W. Birk
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, USA
- *Correspondence to: John W. Birk, Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT 06030, USA. E-mail:
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22
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Martinez-Insfran LA, Ramirez P, Cascales P, Alconchel F, Ferreras D, Febrero B, Martinez M, González MR, Sanchez-Bueno F, Robles R, Parrilla P. Early Outcomes of Liver Transplantation Using Donors After Circulatory Death in Patients With Hepatocellular Carcinoma: A Comparative Study. Transplant Proc 2019; 51:359-364. [PMID: 30879541 DOI: 10.1016/j.transproceed.2018.10.021] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2018] [Accepted: 10/23/2018] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Donation after circulatory death (DCD) has increased in the last decade, although a slight increase in surgical complications has been reported in liver transplantation (LT). Therefore, DCD is not overall recommended because it entails an added risk. However, DCD in selected patients shows acceptable results. OBJECTIVE The objective was to analyze the characteristics, early outcomes, and survival at 1 year post-LT from a single institute (January 2015 to May 2017). MATERIALS AND METHODS We included 18 DCD-LTs and compared them with a control group of 18 donation after brain death (DBD) LTs. We analyzed pre- and posttransplant variables related to donors, recipients, and intraoperative early outcomes within patients transplanted due to hepatocellular carcinoma (HCC). A descriptive analysis, Mann-Whitney U test, χ2, or Fisher test was performed when appropriate, as well as multivariate analysis in case of statistical significance. A variable is considered as statistically significant when it reaches a value of P < .05. RESULTS In DBD, we found a lower length of stay in the intensive care unit before retrieval and a higher rate of alcoholism and diabetes mellitus, Model for End-Stage Liver Disease score, and Child B and C score (P < .05). Most of the DCD were originally from the same LT recipient center, and a higher donor mean post-LT alanine aminotransferase level was found (P < .05). Survival for the DBD group was 88% and 75% in the DCD group at 1 year post-LT, being not significant (NS). CONCLUSION HCC recipients who are transplanted with good quality DCD livers do no worse than those transplanted with livers from DBD donors, although a good selection of them is crucial.
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Affiliation(s)
- L A Martinez-Insfran
- General and Digestive Surgery Department, University Hospital Virgen de la Arrixaca, El Palmar, Murcia, Spain.
| | - P Ramirez
- General and Digestive Surgery Department, University Hospital Virgen de la Arrixaca, El Palmar, Murcia, Spain
| | - P Cascales
- General and Digestive Surgery Department, University Hospital Virgen de la Arrixaca, El Palmar, Murcia, Spain
| | - F Alconchel
- General and Digestive Surgery Department, University Hospital Virgen de la Arrixaca, El Palmar, Murcia, Spain
| | - D Ferreras
- General and Digestive Surgery Department, University Hospital Virgen de la Arrixaca, El Palmar, Murcia, Spain
| | - B Febrero
- General and Digestive Surgery Department, University Hospital Virgen de la Arrixaca, El Palmar, Murcia, Spain
| | - M Martinez
- Intensive Care Unit, University Hospital Virgen de la Arrixaca, El Palmar, Murcia, Spain
| | - M R González
- Hepatology Unit, University Hospital Virgen de la Arrixaca, El Palmar, Murcia, Spain
| | - F Sanchez-Bueno
- General and Digestive Surgery Department, University Hospital Virgen de la Arrixaca, El Palmar, Murcia, Spain
| | - R Robles
- General and Digestive Surgery Department, University Hospital Virgen de la Arrixaca, El Palmar, Murcia, Spain
| | - P Parrilla
- General and Digestive Surgery Department, University Hospital Virgen de la Arrixaca, El Palmar, Murcia, Spain
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Verma R, Satapathy SK. Medical Course and Complications After Liver Transplantation. PSYCHOSOCIAL CARE OF END-STAGE ORGAN DISEASE AND TRANSPLANT PATIENTS 2019:169-179. [DOI: 10.1007/978-3-319-94914-7_14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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24
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Jayant K, Reccia I, Virdis F, Shapiro AMJ. Systematic Review and Meta-Analysis on the Impact of Thrombolytic Therapy in Liver Transplantation Following Donation after Circulatory Death. J Clin Med 2018; 7:425. [PMID: 30413051 PMCID: PMC6262573 DOI: 10.3390/jcm7110425] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Revised: 11/02/2018] [Accepted: 11/06/2018] [Indexed: 02/06/2023] Open
Abstract
AIM The livers from DCD (donation after cardiac death) donations are often envisaged as a possible option to bridge the gap between the availability and increasing demand of organs for liver transplantation. However, DCD livers possess a heightened risk for complications and represent a formidable management challenge. The aim of this study was to evaluate the effects of thrombolytic flush in DCD liver transplantation. METHODS An extensive search of the literature database was made on MEDLINE, EMBASE, Cochrane, Crossref, Scopus databases, and clinical trial registry on 20 September 2018 to assess the role of thrombolytic tissue plasminogen activator (tPA) flush in DCD liver transplantation. RESULTS A total of four studies with 249 patients in the tPA group and 178 patients in the non-tPA group were included. The pooled data revealed a significant decrease in ischemic-type biliary lesions (ITBLs) (P = 0.04), re-transplantation rate (P = 0.0001), and no increased requirement of blood transfusion (P = 0.16) with a better one year graft survival (P = 0.02). CONCLUSIONS To recapitulate, tPA in DCD liver transplantation decreased the incidence of ITBLs, re-transplantation and markedly improved 1-year graft survival, without any increased risk for blood transfusion, hence it has potential to expand the boundaries of DCD liver transplantation.
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Affiliation(s)
- Kumar Jayant
- Department of Surgery and Cancer, Imperial College London, London W12 OHS, UK.
| | - Isabella Reccia
- Department of Surgery and Cancer, Imperial College London, London W12 OHS, UK.
| | | | - A M James Shapiro
- Department of Surgery, University of Alberta, Edmonton, AB T6G 2B7, Canada.
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25
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Angelico R, Perera MTPR, Manzia TM, Parente A, Grimaldi C, Spada M. Donation after Circulatory Death in Paediatric Liver Transplantation: Current Status and Future Perspectives in the Machine Perfusion Era. BIOMED RESEARCH INTERNATIONAL 2018; 2018:1756069. [PMID: 29744353 PMCID: PMC5878911 DOI: 10.1155/2018/1756069] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/21/2017] [Accepted: 02/14/2018] [Indexed: 02/06/2023]
Abstract
Efforts have been made by the transplant community to expand the deceased donor pool in paediatric liver transplantation (LT). The growing experience on donation after circulatory death (DCD) for adult LT has encouraged its use also in children, albeit in selective cases, opening new perspectives for paediatric patients. Even though there has recently been a slight increase in the number of DCD livers transplanted in children, with satisfactory graft and patient outcomes, the use of DCD grafts in paediatric recipients is still controversial due to morbid outcomes associated with DCD grafts. In this context, recent advances in the optimization of donor support by extracorporeal membrane oxygenation and in the graft preservation by liver machine perfusion could find application in order to expand the donor pool in paediatric LT. In the present study we review the current literature on DCD liver grafts transplanted in children and on the use of extracorporeal donor support and liver perfusion machines in paediatrics, with the aim of defining the current status and future perspectives of paediatric LT.
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Affiliation(s)
- Roberta Angelico
- Division of Abdominal Transplantation and Hepatobiliopancreatic Surgery, Bambino Gesù Children's Research Hospital IRCCS, Rome, Italy
| | | | - Tommaso Maria Manzia
- Department of Experimental Medicine and Surgery, Liver Unit, Tor Vergata University of Rome, Rome, Italy
| | - Alessandro Parente
- Department of Experimental Medicine and Surgery, Liver Unit, Tor Vergata University of Rome, Rome, Italy
| | - Chiara Grimaldi
- Division of Abdominal Transplantation and Hepatobiliopancreatic Surgery, Bambino Gesù Children's Research Hospital IRCCS, Rome, Italy
| | - Marco Spada
- Division of Abdominal Transplantation and Hepatobiliopancreatic Surgery, Bambino Gesù Children's Research Hospital IRCCS, Rome, Italy
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26
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Schlegel A, Kalisvaart M, Scalera I, Laing RW, Mergental H, Mirza DF, Perera T, Isaac J, Dutkowski P, Muiesan P. The UK DCD Risk Score: A new proposal to define futility in donation-after-circulatory-death liver transplantation. J Hepatol 2018; 68:456-464. [PMID: 29155020 DOI: 10.1016/j.jhep.2017.10.034] [Citation(s) in RCA: 186] [Impact Index Per Article: 26.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2017] [Revised: 10/17/2017] [Accepted: 10/25/2017] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS Primary non-function and ischaemic cholangiopathy are the most feared complications following donation-after-circulatory-death (DCD) liver transplantation. The aim of this study was to design a new score on risk assessment in liver-transplantation DCD based on donor-and-recipient parameters. METHODS Using the UK national DCD database, a risk analysis was performed in adult recipients of DCD liver grafts in the UK between 2000 and 2015 (n = 1,153). A new risk score was calculated (UK DCD Risk Score) on the basis of a regression analysis. This is validated using the United Network for Organ Sharing database (n = 1,617) and our own DCD liver-transplant database (n = 315). Finally, the new score was compared with two other available prediction systems: the DCD risk scores from the University of California, Los Angeles and King's College Hospital, London. RESULTS The following seven strongest predictors of DCD graft survival were identified: functional donor warm ischaemia, cold ischaemia, recipient model for end-stage liver disease, recipient age, donor age, previous orthotopic liver transplantation, and donor body mass index. A combination of these risk factors (UK DCD risk model) stratified the best recipients in terms of graft survival in the entire UK DCD database, as well as in the United Network for Organ Sharing and in our own DCD population. Importantly, the UK DCD Risk Score significantly predicted graft loss caused by primary non-function or ischaemic cholangiopathy in the futile group (>10 score points). The new prediction model demonstrated a better C statistic of 0.79 compared to the two other available systems (0.71 and 0.64, respectively). CONCLUSIONS The UK DCD Risk Score is a reliable tool to detect high-risk and futile combinations of donor-and-recipient factors in DCD liver transplantation. It is simple to use and offers a great potential for making better decisions on which DCD graft should be rejected or may benefit from functional assessment and further optimization by machine perfusion. LAY SUMMARY In this study, we provide a new prediction model for graft loss in donation-after-circulatory-death (DCD) liver transplantation. Based on UK national data, the new UK DCD Risk Score involves the following seven clinically relevant risk factors: donor age, donor body mass index, functional donor warm ischaemia, cold storage, recipient age, recipient laboratory model for end-stage liver disease, and retransplantation. Three risk classes were defined: low risk (0-5 points), high risk (6-10 points), and futile (>10 points). This new model stratified best in terms of graft survival compared to other available models. Futile combinations (>10 points) achieved an only very limited 1- and 5-year graft survival of 37% and less than 20%, respectively. In contrast, an excellent graft survival has been shown in low-risk combinations (≤5 points). The new model is easy to calculate at the time of liver acceptance. It may help to decide which risk combination will benefit from additional graft treatment, or which DCD liver should be declined for a certain recipient.
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Affiliation(s)
- Andrea Schlegel
- The Liver Unit, Queen Elizabeth University Hospital Birmingham, Birmingham, UK
| | - Marit Kalisvaart
- The Liver Unit, Queen Elizabeth University Hospital Birmingham, Birmingham, UK
| | - Irene Scalera
- The Liver Unit, Queen Elizabeth University Hospital Birmingham, Birmingham, UK
| | - Richard W Laing
- The Liver Unit, Queen Elizabeth University Hospital Birmingham, Birmingham, UK
| | - Hynek Mergental
- The Liver Unit, Queen Elizabeth University Hospital Birmingham, Birmingham, UK
| | - Darius F Mirza
- The Liver Unit, Queen Elizabeth University Hospital Birmingham, Birmingham, UK
| | - Thamara Perera
- The Liver Unit, Queen Elizabeth University Hospital Birmingham, Birmingham, UK
| | - John Isaac
- The Liver Unit, Queen Elizabeth University Hospital Birmingham, Birmingham, UK
| | - Philipp Dutkowski
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Zurich, Switzerland
| | - Paolo Muiesan
- The Liver Unit, Queen Elizabeth University Hospital Birmingham, Birmingham, UK.
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27
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Junger HH, Schlitt HJ, Geissler EK, Fichtner-Feigl S, Brunner SM. Bile duct regeneration and immune response by passenger lymphocytes signals biliary recovery versus complications after liver transplantation. Liver Transpl 2017; 23:1422-1432. [PMID: 28779549 DOI: 10.1002/lt.24836] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Revised: 06/30/2017] [Accepted: 07/24/2017] [Indexed: 01/05/2023]
Abstract
This study aimed to elucidate the impact of epithelial regenerative responses and immune cell infiltration on biliary complications after liver transplantation. Bile duct (BD) damage after cold storage was quantified by a BD damage score and correlated with patient outcome in 41 patients. Bacterial infiltration was determined by fluorescence in situ hybridization (FISH). BD samples were analyzed by immunohistochemistry for E-cadherin, cytokeratin, CD56, CD14, CD4, CD8, and double-immunofluorescence for cytokine production and by messenger RNA (mRNA) microarray. Increased mRNA levels of adherens junctions (P < 0.01) were detected in damaged BDs from patients without complications compared with damaged BDs from patients with biliary complications. Immunohistochemistry showed increased expression of E-cadherin and cytokeratin in BDs without biliary complications (P = 0.03; P = 0.047). FISH analysis demonstrated translocation of bacteria in BDs. However, mRNA analysis suggested an enhanced immune response in BDs without biliary complications (P < 0.01). Regarding immune cell infiltration, CD4+ and CD8+ cells were significantly increased in patients without complications compared with those with complications (P = 0.02; P = 0.01). In conclusion, following BD damage during cold storage, we hypothesize that the functional regenerative capacity of biliary epithelium and enhanced local adaptive immune cell infiltration are crucial for BD recovery. Such molecular immunological BD analyses therefore could help to predict biliary complications in cases of "major" epithelial damage after cold storage.Liver Transplantation 23 1422-1432 2017 AASLD.
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Affiliation(s)
- Henrik H Junger
- Department of Surgery, University Medical Center Regensburg, Regensburg, Germany
| | - Hans J Schlitt
- Department of Surgery, University Medical Center Regensburg, Regensburg, Germany
| | - Edward K Geissler
- Department of Surgery, University Medical Center Regensburg, Regensburg, Germany
| | - Stefan Fichtner-Feigl
- Department of Surgery, University Medical Center Regensburg, Regensburg, Germany.,Department of General and Visceral Surgery, University Medical Center Freiburg, Freiburg, Germany
| | - Stefan M Brunner
- Department of Surgery, University Medical Center Regensburg, Regensburg, Germany
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Sirtuin 1 Stimulation Attenuates Ischemic Liver Injury and Enhances Mitochondrial Recovery and Autophagy. Crit Care Med 2017; 44:e651-63. [PMID: 26963320 DOI: 10.1097/ccm.0000000000001637] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
OBJECTIVES Hepatic ischemia-reperfusion is a major clinical problem with limited treatment options. The pathophysiology of hepatic ischemia-reperfusion is characterized by mitochondrial dysfunction and cellular energy deficits. Sirtuin 1 is an energy-sensing enzyme known to modulate mitochondrial biogenesis. We hypothesized that pharmacologic activation of sirtuin 1 is protective after hepatic ischemia-reperfusion injury. DESIGN Animal study. SETTING University-based experimental laboratory. SUBJECTS Wild-type C57BL/6 mice. INTERVENTIONS C57BL/6 mice were subjected to 60-minute partial hepatic ischemia-reperfusion and posttreated with sirtuin 1 activator, SRT1720 (20 mg/kg), or vehicle. Blood and liver were collected at 24 hours after ischemia-reperfusion for analyses of hepatic injury, adenosine triphosphate levels, mitochondrial mass, autophagy, inflammation, and oxidative stress. H4IIE hepatoma cells and rat primary hepatocytes were incubated with oxyrase to induce hypoxia followed by reoxygenation in the presence or absence of SRT1720 for assessment of mitochondrial mass, mitochondrial membrane potential, and autophagy. MEASUREMENTS AND MAIN RESULTS SRT1720 restored the reduction in mitochondrial mass, enhanced autophagy, and preserved adenosine triphosphate levels in the liver after ischemia-reperfusion, which was associated with a decrease in ischemia-reperfusion-induced hepatic injury, apoptosis, and necrosis. Ischemia-reperfusion-induced inflammation was also significantly reduced by SRT1720 as measured by systemic and hepatic cytokine and chemokine levels, as well as a decrease in neutrophil infiltration to the liver. Furthermore, oxidative stress was markedly attenuated in the SRT1720-treated mice compared with the vehicle. SRT1720 treatment increased adenosine triphosphate levels and survival of cultured hepatocytes after hypoxia-reoxygenation. SRT1720 not only increased the mitochondrial mass but also increased mitochondrial membrane potential per cell in cultured hepatocytes after hypoxia-reoxygenation. Moreover, SRT1720 prevented the hypoxia-reoxygenation-induced mitochondrial depolarization and resulted in an enhancement of autophagy in cultured hepatocytes after hypoxia-reoxygenation. CONCLUSIONS Pharmacologic stimulation of sirtuin 1 attenuates liver injury after hepatic ischemia-reperfusion by restoring mitochondrial mass and membrane potential, which is associated with the enhancement of autophagy.
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29
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Eren EA, Latchana N, Beal E, Hayes D, Whitson B, Black SM. Donations After Circulatory Death in Liver Transplant. EXP CLIN TRANSPLANT 2016; 14:463-470. [PMID: 27733105 PMCID: PMC5461820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
The supply of liver grafts for treatment of end-stage liver disease continues to fall short of ongoing demands. Currently, most liver transplants originate from donations after brain death. Enhanced utilization of the present resources is prudent to address the needs of the population. Donation after circulatory or cardiac death is a mechanism whereby the availability of organs can be expanded. Donations after circulatory death pose unique challenges given their exposure to warm ischemia. Technical principles of donations after circulatory death procurement and pertinent studies investigating patient outcomes, graft outcomes, and complications are highlighted in this review. We also review associated risk factors to suggest potential avenues to achieve improved outcomes and reduced complications. Future considerations and alternative techniques of organ preservation are discussed, which may suggest novel strategies to enhance preservation and donor expansion through the use of marginal donors. Ultimately, without effective measures to bolster organ supply, donations after circulatory death should remain a consideration; however, an understanding of inherent risks and limitations is necessary.
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Affiliation(s)
- Emre A. Eren
- Department of Surgery, Division of Transplantation, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
- The Collaboration for Organ Perfusion, Protection, Engineering and Regeneration (COPPER) Laboratory, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Nicholas Latchana
- Department of Surgery, Division of Transplantation, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Eliza Beal
- Department of Surgery, Division of Transplantation, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
- The Collaboration for Organ Perfusion, Protection, Engineering and Regeneration (COPPER) Laboratory, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Don Hayes
- Departments of Pediatrics and Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
- Section of Pulmonary Medicine, Nationwide Children’s Hospital, Columbus, Ohio, USA
| | - Bryan Whitson
- Department of Surgery, Division of Cardiac Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
- The Collaboration for Organ Perfusion, Protection, Engineering and Regeneration (COPPER) Laboratory, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Sylvester M. Black
- Department of Surgery, Division of Transplantation, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
- The Collaboration for Organ Perfusion, Protection, Engineering and Regeneration (COPPER) Laboratory, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
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30
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Laskey HL, Schomaker N, Hung KW, Asrani SK, Jennings L, Nydam TL, Gralla J, Wiseman A, Rosen HR, Biggins SW. Predicting renal recovery after liver transplant with severe pretransplant subacute kidney injury: The impact of warm ischemia time. Liver Transpl 2016; 22:1085-91. [PMID: 27302834 DOI: 10.1002/lt.24488] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2015] [Revised: 05/06/2016] [Accepted: 05/12/2016] [Indexed: 01/13/2023]
Abstract
Identifying which liver transplantation (LT) candidates with severe kidney injury will have a full recovery of renal function after liver transplantation alone (LTA) is difficult. Avoiding unnecessary simultaneous liver-kidney transplantation (SLKT) can optimize the use of scarce kidney grafts. Incorrect predictions of spontaneous renal recovery after LTA can lead to increased morbidity and mortality. We retrospectively analyzed all LTA patients at our institution from February 2002 to February 2013 (n = 583) and identified a cohort with severe subacute renal injury (n = 40; creatinine <2 mg/dL in the 14-89 days prior to LTA and not on renal replacement therapy [RRT] yet, ≥2 mg/dL within 14 days of LTA and/or on RRT). Of 40 LTA recipients, 26 (65%) had renal recovery and 14 (35%) did not. The median (interquartile range) warm ischemia time (WIT) in recipients with and without renal recovery after LTA was 31 minutes (24-46 minutes) and 39 minutes (34-49 minutes; P = 0.02), respectively. Adjusting for the severity of the subacute kidney injury with either Acute Kidney Injury Network or Risk, Injury, Failure, Loss, and End-Stage Kidney Disease criteria, increasing WIT was associated with lack of renal recovery (serum creatinine <2 mg/dL after LTA, not on RRT), with an odds ratio (OR) of 1.08 (1.01-1.16; P = 0.03) and 1.09 (1.01-1.17; P = 0.02), respectively. For each minute of increased WIT, there was an 8%-9% increase in the risk of lack of renal recovery after LTA. In a separate cohort of 98 LTA recipients with subacute kidney injury, we confirmed the association of WIT and lack of renal recovery (OR, 1.04; P = 0.04). In LT candidates with severe subacute renal injury, operative measures to minimize WIT may improve renal recovery potentially avoiding RRT and the need for subsequent kidney transplant. Liver Transplantation 22 1085-1091 2016 AASLD.
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Affiliation(s)
- Heather L Laskey
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, CO
| | - Nathan Schomaker
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, CO
| | - Kenneth W Hung
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, CO
| | - Sumeet K Asrani
- Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX
| | - Linda Jennings
- Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX
| | - Trevor L Nydam
- Department of Surgery, University of Colorado Denver, Denver, CO
| | - Jane Gralla
- Department of Pediatrics and Biostatistics and Informatics, University of Colorado Denver, Denver, CO
| | - Alex Wiseman
- Division of Nephrology, University of Colorado Denver, Denver, CO
| | - Hugo R Rosen
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, CO
| | - Scott W Biggins
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, CO
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31
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Fenkel JM, Halegoua-DeMarzio DL. Management of the Liver Transplant Recipient: Approach to Allograft Dysfunction. Med Clin North Am 2016; 100:477-86. [PMID: 27095640 DOI: 10.1016/j.mcna.2016.01.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Liver transplant (LT) recipients are living longer than ever today and many will experience some form of allograft dysfunction. The common causes of allograft dysfunction vary significantly depending on the timing since LT. Most allograft abnormalities are manageable with minimally invasive procedures, medications, and lifestyle modification. The most common differential diagnoses by time period after LT, and diagnostic and management considerations, are highlighted. Collaboration and comanagement of LT recipients between primary care and the transplant hepatologist is essential for optimizing recipient and allograft outcomes.
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Affiliation(s)
- Jonathan M Fenkel
- Division of Gastroenterology and Hepatology, Department of Medicine, Sidney Kimmel Medical College at Thomas Jefferson University, 132 South 10th Street, Suite 480, Main Building, Philadelphia, PA 19107, USA.
| | - Dina L Halegoua-DeMarzio
- Division of Gastroenterology and Hepatology, Department of Medicine, Sidney Kimmel Medical College at Thomas Jefferson University, 132 South 10th Street, Suite 480, Main Building, Philadelphia, PA 19107, USA
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32
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Mancinelli R, Glaser S, Francis H, Carpino G, Franchitto A, Vetuschi A, Sferra R, Pannarale L, Venter J, Meng F, Alpini G, Onori P, Gaudio E. Ischemia reperfusion of the hepatic artery induces the functional damage of large bile ducts by changes in the expression of angiogenic factors. Am J Physiol Gastrointest Liver Physiol 2015; 309:G865-73. [PMID: 26451003 PMCID: PMC4669349 DOI: 10.1152/ajpgi.00015.2015] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2015] [Accepted: 09/08/2015] [Indexed: 02/06/2023]
Abstract
Liver transplantation and cholangiocarcinoma induce biliary dysfunction following ischemia reperfusion (IR). The function of the intrahepatic biliary tree is regulated by both autocrine and paracrine factors. The aim of the study was to demonstrate that IR-induced damage of cholangiocytes is associated with altered expression of biliary angiogenic factors. Normal and bile duct ligation rats underwent 24-h sham or hepatic reperfusion after 30 min of transient occlusion of the hepatic artery (HAIR) or portal vein (PVIR) before collecting liver blocks and cholangiocyte RNA or protein. We evaluated liver histology, biliary apoptosis, proliferation and expression of VEGF-A/C, VEGFR-2/3, Ang-1/2, and Tie-1/2 in liver sections and isolated small and large cholangiocytes. Normal rat intrahepatic cholangiocyte cultures (NRICC) were maintained under standard conditions in normoxic or under a hypoxic atmosphere for 4 h and then transferred to normal conditions for selected times. Subsequently, we measured changes in biliary proliferation and apoptosis and the expression of VEGF-A/C and VEGFR-2/3. In vivo, HAIR (but not PVIR) induced damage of large bile ducts and decreased proliferation and secretin-stimulated cAMP levels. HAIR-induced damage of large bile ducts was associated with increased expression of VEGF-A/C, VEGFR-2/3, Ang-1/2, and Tie-1/2. In vitro, under hypoxic conditions, there was increased apoptosis and reduced proliferation of NRICC concomitant with enhanced expression of VEGF-A/C and VEGFR-2/3. The functional damage of large bile ducts by HAIR and hypoxia is associated with increased expression of angiogenic factors in small cholangiocytes, presumably due to a compensatory mechanism in response to biliary damage.
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Affiliation(s)
- Romina Mancinelli
- 1Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza, Rome, Italy;
| | - Shannon Glaser
- 2Research, Central Texas Veterans Health Care System, Temple, Texas; ,3Scott & White Digestive Disease Research Center, Baylor Scott & White, Temple, Texas; ,4Department of Medicine, Division Gastroenterology, Texas A&M University Health Science Center, College of Medicine, Temple, Texas;
| | - Heather Francis
- 2Research, Central Texas Veterans Health Care System, Temple, Texas; ,3Scott & White Digestive Disease Research Center, Baylor Scott & White, Temple, Texas; ,4Department of Medicine, Division Gastroenterology, Texas A&M University Health Science Center, College of Medicine, Temple, Texas;
| | - Guido Carpino
- 1Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza, Rome, Italy;
| | - Antonio Franchitto
- 1Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza, Rome, Italy; ,6Eleonora Lorillard Spencer Cenci Foundation, Rome, Italy
| | - Antonella Vetuschi
- 5Department of Biotechnological and Applied Clinical Sciences, University of L′Aquila, L′Aquila, Italy;
| | - Roberta Sferra
- 5Department of Biotechnological and Applied Clinical Sciences, University of L′Aquila, L′Aquila, Italy;
| | - Luigi Pannarale
- 1Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza, Rome, Italy;
| | - Julie Venter
- 4Department of Medicine, Division Gastroenterology, Texas A&M University Health Science Center, College of Medicine, Temple, Texas;
| | - Fanyin Meng
- 2Research, Central Texas Veterans Health Care System, Temple, Texas; ,3Scott & White Digestive Disease Research Center, Baylor Scott & White, Temple, Texas; ,4Department of Medicine, Division Gastroenterology, Texas A&M University Health Science Center, College of Medicine, Temple, Texas;
| | - Gianfranco Alpini
- 2Research, Central Texas Veterans Health Care System, Temple, Texas; ,3Scott & White Digestive Disease Research Center, Baylor Scott & White, Temple, Texas; ,4Department of Medicine, Division Gastroenterology, Texas A&M University Health Science Center, College of Medicine, Temple, Texas;
| | - Paolo Onori
- Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza, Rome, Italy;
| | - Eugenio Gaudio
- 1Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza, Rome, Italy;
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Late liver function test abnormalities post-adult liver transplantation: a review of the etiology, investigation, and management. Hepatol Int 2015; 10:106-14. [PMID: 26603541 DOI: 10.1007/s12072-015-9685-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2015] [Accepted: 11/06/2015] [Indexed: 12/14/2022]
Abstract
Approximately 24,000 liver transplants are performed annually worldwide, almost 7000 of which are performed in the USA. Survival is excellent and continues to improve, with 1-year survival currently exceeding 85 %, but effective management of patients after liver transplantation is critical to achieve optimal results. A plethora of diseases can affect the transplanted allograft, ranging from recurrence of the original disease to de novo liver pathology, and diagnosis can be complicated by nonclassical presentation, de novo disease, or inconclusive histology. Patients can remain asymptomatic despite significant damage to the transplanted liver, so prompt identification and treatment of liver disease after transplantation is crucial to preserve allograft function. Liver function tests are routinely taken throughout the postoperative period to monitor the graft. Although nonspecific, they are inexpensive, noninvasive, and sensitive for allograft disease and can quickly alert physicians to the presence of asymptomatic pathology. This review will outline possible causes of liver function test abnormalities in the late posttransplant period and provide guidance for investigation, diagnosis, and management.
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Woodside KJ, Goldfarb DA, Rabets JC, Sanchez EQ, Lebovitz DJ, Schulak JA, Fung JJ, Eghtesad B. Enhancing kidney function with thrombolytic therapy following donation after cardiac death: a multicenter quasi-blinded prospective randomized trial. Clin Transplant 2015; 29:1173-80. [PMID: 26448622 DOI: 10.1111/ctr.12647] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/04/2015] [Indexed: 12/21/2022]
Abstract
Kidneys from donors after cardiac death (DCD) are at risk for inferior outcomes, possibly due to microthrombi and additional warm ischemia. We describe an organ procurement organization-wide trial utilizing thrombolytic tissue plasminogen activator (tPA) during machine pulsatile perfusion (MPP). A kidney from each recovered kidney pair was prospectively randomized to receive tPA (50 mg Alteplase) or no tPA (control) in the MPP perfusate. From 2011 to 2013, 24 kidneys were placed with enrolled recipients from 19 DCD kidney donors. There were no significant differences for absolute values of flow or resistance while undergoing MPP between the groups, nor rates of achieving discrete flow and resistance targets. While there was a trend toward lower creatinine and higher glomerular filtration rates in the tPA group at 3, 6, 9, and 12 months, these differences were not significant. Delayed graft function (DGF) rates were 41.7% in the tPA group vs. 58.4% in the control group (OR 0.51, 95%CI 0.10-2.59, p = 0.68). Death-censored graft survival was similar between the groups. In this pilot study, encouraging trends are seen in kidney allograft function independent of MPP parameters following DCD kidney transplantation for those kidneys receiving thrombolytic tPA and MPP, compared with standard MPP.
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Affiliation(s)
- Kenneth J Woodside
- Transplant Institute, University Hospitals Case Medical Center, Cleveland, OH, USA
| | | | - John C Rabets
- Transplant Center, Cleveland Clinic, Cleveland, OH, USA
| | - Edmund Q Sanchez
- Transplant Institute, University Hospitals Case Medical Center, Cleveland, OH, USA
| | - Daniel J Lebovitz
- Lifebanc, Cleveland, OH, USA.,Critical Care, Akron Children's Hospital, Akron, OH, USA
| | - James A Schulak
- Transplant Institute, University Hospitals Case Medical Center, Cleveland, OH, USA
| | - John J Fung
- Transplant Center, Cleveland Clinic, Cleveland, OH, USA
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Halldorson JB, Rayhill S, Bakthavatsalam R, Montenovo M, Dick A, Perkins J, Reyes J. Serum alkaline phosphatase and bilirubin are early surrogate markers for ischemic cholangiopathy and graft failure in liver transplantation from donation after circulatory death. Transplant Proc 2015; 47:465-8. [PMID: 25769592 DOI: 10.1016/j.transproceed.2014.10.055] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2014] [Revised: 10/15/2014] [Accepted: 10/28/2014] [Indexed: 01/08/2023]
Abstract
Liver transplantation with the use of donation after circulatory death (DCD) is associated with ischemic cholangiopathy (IC) often leading to graft loss. We hypothesized that serial postoperative analysis of alkaline phosphatase and bilirubin might identify patients who would later on develop ischemic cholangiopathy and/or graft loss, allowing early recognition and potentially retransplantation. The University of Washington DCD experience totals 89 DCD liver transplantations performed from 2003 to 2011 with Kaplan-Meier estimated 5-year patient and graft survival rates of 81.6% and 75.6%, respectively; 84/89 patients transplanted with DCD livers lived ≥ 60 days after transplantation and were analyzed. Serum bilirubin and alkaline phosphatase levels at 1 week, 2 week, 1 month, and 2 months after transplantation were analyzed. Two-month serum bilirubin and alkaline phosphatase proved to have the strongest associations with development of IC and graft failure. Two-month alkaline phosphatase of <100 U/L had a negative predictive value of 97% for development of IC. Two-month alkaline phosphatase demonstrated an inflection starting at >300 U/L strongly associated with development of IC (P < .0001). Serum bilirubin at 2 months was most strongly associated with graft failure within the 1st year with a strong inflection point at 2.5 mg/dL (P = .0001). All jaundiced recipients at 60 days after transplantation (bilirubin >2.5 mg/dL) developed graft failure within the 1st year (P < .0001). Use of these early surrogate markers could facilitate prioritization and early retransplantation for DCD liver recipients with allografts destined for failure.
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Affiliation(s)
- J B Halldorson
- Division of Transplantation, University of California, San Diego, California.
| | - S Rayhill
- Division of Transplantation, University of Washington, Seattle, Washington
| | - R Bakthavatsalam
- Division of Transplantation, University of Washington, Seattle, Washington
| | - M Montenovo
- Division of Transplantation, University of Washington, Seattle, Washington
| | - A Dick
- Division of Transplantation, University of Washington, Seattle, Washington
| | - J Perkins
- Division of Transplantation, University of Washington, Seattle, Washington
| | - J Reyes
- Division of Transplantation, University of Washington, Seattle, Washington
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Senoo T, Ichikawa T, Taura N, Miyaaki H, Miuma S, Shibata H, Honda T, Takatsuki M, Hidaka M, Soyama A, Eguchi S, Nakao K. Incidence of and risk factors for bile duct stones after living donor liver transplantation: An analysis of 100 patients. Hepatol Res 2015; 45:969-975. [PMID: 25331775 DOI: 10.1111/hepr.12438] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2014] [Revised: 09/25/2014] [Accepted: 10/14/2014] [Indexed: 12/13/2022]
Abstract
AIM Although bile duct stone (BDS) is one of the biliary complications of liver transplantation, analytical studies, particularly on living donor liver transplantation (LDLT) cases, are rare. This study aimed to clarify the incidence of and risk factors for BDS following LDLT. METHODS We retrospectively reviewed the medical records of 100 patients who underwent LDLT at our institute from August 2000 to May 2012, and analyzed their clinical characteristics and risk factors for BDS. RESULTS Of these, 10 patients (10.0%) developed BDS during the observation period. The median follow-up period to BDS diagnosis was 45.5 months (range, 5-84) after LDLT. Univariate analysis revealed male sex, right lobe graft and bile duct strictures as factors that significantly correlated with BDS formation. Multivariate analysis revealed bile duct strictures (odds ratio, 7.17; P = 0.011) and right lobe graft (odds ratio, 10.20; P = 0.040) to be independent risk factors for BDS formation. One patient with BDS and biliary strictures succumbed to sepsis from cholangitis. CONCLUSION In the present study, right lobe graft and bile duct strictures are independent risk factors for BDS formation after LDLT. More careful observation and monitoring are required in the patients with high-risk factors.
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Affiliation(s)
- Takemasa Senoo
- Department of Gastroenterology and Hepatology, Nagasaki University, Nagasaki, Japan
| | - Tatsuki Ichikawa
- Department of Gastroenterology and Hepatology, Nagasaki University, Nagasaki, Japan
| | - Naota Taura
- Department of Gastroenterology and Hepatology, Nagasaki University, Nagasaki, Japan
| | - Hisamitsu Miyaaki
- Department of Gastroenterology and Hepatology, Nagasaki University, Nagasaki, Japan
| | - Satoshi Miuma
- Department of Gastroenterology and Hepatology, Nagasaki University, Nagasaki, Japan
| | - Hidetaka Shibata
- Department of Gastroenterology and Hepatology, Nagasaki University, Nagasaki, Japan
| | - Takuya Honda
- Department of Gastroenterology and Hepatology, Nagasaki University, Nagasaki, Japan
| | - Mitsuhisa Takatsuki
- Department of Surgery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
| | - Masaaki Hidaka
- Department of Surgery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
| | - Akihiko Soyama
- Department of Surgery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
| | - Susumu Eguchi
- Department of Surgery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
| | - Kazuhiko Nakao
- Department of Gastroenterology and Hepatology, Nagasaki University, Nagasaki, Japan
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Liver Transplantation Using Grafts from Donation After Cardiac Death Donors. CURRENT SURGERY REPORTS 2015. [DOI: 10.1007/s40137-015-0105-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Visrodia KH, Tabibian JH, Baron TH. Endoscopic management of benign biliary strictures. World J Gastrointest Endosc 2015; 7:1003-1013. [PMID: 26322153 PMCID: PMC4549657 DOI: 10.4253/wjge.v7.i11.1003] [Citation(s) in RCA: 15] [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: 04/28/2015] [Revised: 06/25/2015] [Accepted: 08/03/2015] [Indexed: 02/05/2023] Open
Abstract
Endoscopic management of biliary obstruction has evolved tremendously since the introduction of flexible fiberoptic endoscopes over 50 years ago. For the last several decades, endoscopic retrograde cholangiopancreatography (ERCP) has become established as the mainstay for definitively diagnosing and relieving biliary obstruction. In addition, and more recently, endoscopic ultrasonography (EUS) has gained increasing favor as an auxiliary diagnostic and therapeutic modality in facilitating decompression of the biliary tree. Here, we provide a review of the current and continually evolving role of gastrointestinal endoscopy, including both ERCP and EUS, in the management of biliary obstruction with a focus on benign biliary strictures.
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Management of the Potential Organ Donor in the ICU: Society of Critical Care Medicine/American College of Chest Physicians/Association of Organ Procurement Organizations Consensus Statement. Crit Care Med 2015; 43:1291-325. [PMID: 25978154 DOI: 10.1097/ccm.0000000000000958] [Citation(s) in RCA: 223] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
This document was developed through the collaborative efforts of the Society of Critical Care Medicine, the American College of Chest Physicians, and the Association of Organ Procurement Organizations. Under the auspices of these societies, a multidisciplinary, multi-institutional task force was convened, incorporating expertise in critical care medicine, organ donor management, and transplantation. Members of the task force were divided into 13 subcommittees, each focused on one of the following general or organ-specific areas: death determination using neurologic criteria, donation after circulatory death determination, authorization process, general contraindications to donation, hemodynamic management, endocrine dysfunction and hormone replacement therapy, pediatric donor management, cardiac donation, lung donation, liver donation, kidney donation, small bowel donation, and pancreas donation. Subcommittees were charged with generating a series of management-related questions related to their topic. For each question, subcommittees provided a summary of relevant literature and specific recommendations. The specific recommendations were approved by all members of the task force and then assembled into a complete document. Because the available literature was overwhelmingly comprised of observational studies and case series, representing low-quality evidence, a decision was made that the document would assume the form of a consensus statement rather than a formally graded guideline. The goal of this document is to provide critical care practitioners with essential information and practical recommendations related to management of the potential organ donor, based on the available literature and expert consensus.
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Macías-Gómez C, Dumonceau JM. Endoscopic management of biliary complications after liver transplantation: An evidence-based review. World J Gastrointest Endosc 2015; 7:606-616. [PMID: 26078829 PMCID: PMC4461935 DOI: 10.4253/wjge.v7.i6.606] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2014] [Revised: 01/21/2015] [Accepted: 03/18/2015] [Indexed: 02/05/2023] Open
Abstract
Biliary tract diseases are the most common complications following liver transplantation (LT) and usually include biliary leaks, strictures, and stone disease. Compared to deceased donor liver transplantation in adults, living donor liver transplantation is plagued by a higher rate of biliary complications. These may be promoted by multiple risk factors related to recipient, graft, operative factors and post-operative course. Magnetic resonance cholangiopancreatography is the first-choice examination when a biliary complication is suspected following LT, in order to diagnose and to plan the optimal therapy; its limitations include a low sensitivity for the detection of biliary sludge. For treating anastomotic strictures, balloon dilatation complemented with the temporary placement of multiple simultaneous plastic stents has become the standard of care and results in stricture resolution with no relapse in > 90% of cases. Temporary placement of fully covered self-expanding metal stents (FCSEMSs) has not been demonstrated to be superior (except in a pilot randomized controlled trial that used a special design of FCSEMSs), mostly because of the high migration rate of current FCSEMSs models. The endoscopic approach of non-anastomotic strictures is technically more difficult than that of anastomotic strictures due to the intrahepatic and/or hilar location of strictures, and the results are less satisfactory. For treating biliary leaks, biliary sphincterotomy and transpapillary stenting is the standard approach and results in leak resolution in more than 85% of patients. Deep enteroscopy is a rapidly evolving technique that has allowed successful treatment of patients who were not previously amenable to endoscopic therapy. As a result, the percutaneous and surgical approaches are currently required in a minority of patients.
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Girotra M, Soota K, Klair JS, Dang SM, Aduli F. Endoscopic management of post-liver transplant biliary complications. World J Gastrointest Endosc 2015; 7:446-459. [PMID: 25992185 PMCID: PMC4436914 DOI: 10.4253/wjge.v7.i5.446] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2014] [Revised: 11/15/2014] [Accepted: 02/04/2015] [Indexed: 02/05/2023] Open
Abstract
Biliary complications are being increasingly encountered in post liver transplant patients because of increased volume of transplants and longer survival of these recipients. Overall management of these complications may be challenging, but with advances in endoscopic techniques, majority of such patients are being dealt with by endoscopists rather than the surgeons. Our review article discusses the recent advances in endoscopic tools and techniques that have proved endoscopic retrograde cholangiography with various interventions, like sphincterotomy, bile duct dilatation, and stent placement, to be the mainstay for management of most of these complications. We also discuss the management dilemmas in patients with surgically altered anatomy, where accessing the bile duct is challenging, and the recent strides towards making this prospect a reality.
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Tabibian JH, Girotra M, Yeh HC, Singh VK, Okolo PI, Cameron AM, Gurakar A. Risk factors for early repeat ERCP in liver transplantation patients with anastomotic biliary stricture. Ann Hepatol 2015; 14:340-347. [PMID: 25864214 DOI: 10.1016/s1665-2681(19)31273-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/14/2025]
Abstract
INTRODUCTION Anastomotic biliary strictures (ABS) are a significant clinical problem associated with decreased survival post-liver transplantation (LT). Contributing to the morbidity of ABS is the need for early (i.e. emergent or unplanned) repeat endoscopic retrograde cholangiopancreatographies (ER-ERCPs). Our aim was to determine clinical, operative, and endoscopic predictors of ER-ERCP in patients with ABS. MATERIAL AND METHODS Medical records of 559 patients who underwent LT at our institution from 2000-2012 were retrospectively reviewed for pertinent data. The primary endpoint was need for ER-ERCP. Seventeen potential predictors of ER-ERCP were assessed in bivariate analyses, and those with p < 0.20 were included in multivariate regression models. RESULTS Fifty-four LT patients developed ABS and underwent a total of 200 ERCPs, of which 40 met criteria for ER-ERCP. Predictors of ER-ERCP in bivariate analyses included balloon dilation within 3 months post-LT and donation after cardiac death (both p < 0.05). Balloon dilation within 3 months post-LT was also associated with shorter ER-ERCP-free survival (p = 0.02). Moreover, a significantly higher proportion (67%) of patients who underwent balloon dilation within 3 months post-LT subsequent experienced ≥ 1 ER-ERCP (p = 0.03), and those who experienced ≥ 1 ER-ERCP had lower stricture resolution rates at the end of endoscopic therapy compared to those who did not (79 vs. 97%, p = 0.02). In multivariate analyses, balloon dilation within 3 months post-LT was the strongest predictor of ER-ERCP (OR 3.8, 95% CI 1.7-8.6, p = 0.001). CONCLUSIONS Balloon dilation of ABS within 3 months post-LT is associated with an increased risk of ER-ERCP, which itself is associated with lower ABS resolution rates. Prospective studies are needed to confirm these findings and their implications for endoscopic management and follow-up of post-LT ABS.
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Affiliation(s)
- James H Tabibian
- Division of Gastroenterology, Hepatology, and Transplant Hepatology, Johns Hopkins School of Medicine, Baltimore, MD, USA; Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Mohit Girotra
- Division of Gastroenterology, Hepatology, and Transplant Hepatology, Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - Hsin-Chieh Yeh
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Vikesh K Singh
- Division of Gastroenterology, Hepatology, and Transplant Hepatology, Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - Patrick I Okolo
- Division of Gastroenterology, Hepatology, and Transplant Hepatology, Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - Andrew M Cameron
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Ahmet Gurakar
- Division of Gastroenterology, Hepatology, and Transplant Hepatology, Johns Hopkins School of Medicine, Baltimore, MD, USA
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Halldorson JB, Bakthavatsalam R, Montenovo M, Dick A, Rayhill S, Perkins J, Reyes J. Differential rates of ischemic cholangiopathy and graft survival associated with induction therapy in DCD liver transplantation. Am J Transplant 2015; 15:251-8. [PMID: 25534449 DOI: 10.1111/ajt.12962] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2014] [Revised: 07/09/2014] [Accepted: 08/04/2014] [Indexed: 01/25/2023]
Abstract
Transplantation utilizing donation after circulatory death (DCD) donors is associated with ischemic cholangiopathy (IC) and graft loss. The University of Washington (UW) DCD experience totals 89 DCD liver transplants performed between 2003 and 2011. Overall outcome after DCD liver transplantation at UW demonstrates Kaplan-Meier estimated 5-year patient and graft survival rates of 81.6% and 75.6%, respectively, with the great majority of patient and graft losses occurring in the first-year posttransplant from IC. Our program has almost exclusively utilized either anti-thymocyte globulin (ATG) or basiliximab induction (86/89) for DCD liver transplantations. Analysis of the differential effect of induction agent on graft survival demonstrated graft survival of 96.9% at 1 year for ATG versus 75.9% for basiliximab (p = 0.013). The improved survival did not appear to be from a lower rate of rejection (21.9% vs. 22.2%) but rather a differential rate of IC, 35.2% for basiliximab versus 12.5% for ATG (p = 0.011). Multivariable analysis demonstrated induction agent to be independently associated with graft survival and IC free graft survival when analyzed against variables including donor age, fWIT, donor cold ischemia time and transplant era.
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Affiliation(s)
- J B Halldorson
- Division of Transplantation, University of California, San Diego, CA
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Tauroursodeoxycholic acid and 4-phenyl butyric acid alleviate endoplasmic reticulum stress and improve prognosis of donation after cardiac death liver transplantation in rats. Hepatobiliary Pancreat Dis Int 2014; 13:586-93. [PMID: 25475860 DOI: 10.1016/s1499-3872(14)60269-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Inevitable warm ischemia time before organ procurement aggravates posttransplantation ischemia-reperfusion injury. Endoplasmic reticulum (ER) stress is involved in ischemia-reperfusion injury, but its role in donation after cardiac death (DCD) liver transplantation is not clear and the effect of ER stress inhibitors, tauroursodeoxycholic acid (TUDCA) and 4-phenyl butyric acid (PBA), on the prognosis of recipient of DCD liver transplantation remains unclear. METHODS Male Sprague-Dawley rats (8-10 weeks) were randomly divided into the control group: liver grafts without warm ischemia were implanted; DCD group: warm ischemia time of the liver grafts was 60 minutes; TUDCA and PBA groups: based on the DCD group, donors were intraperitoneally injected with TUDCA or PBA 30 minutes before the organ procurements. Serum aminotransferase levels, oxidative stress activation and expression of ER stress signal molecules were evaluated. Pathological examinations were performed. The survivals of the recipients in each group were compared for 14 days. RESULTS Compared with the control group, DCD rats had significantly higher levels of serum aminotransferase at 6 hours, 1 day and 3 days after operation (P<0.01, 0.01 and 0.05, respectively) and oxidative indices (P<0.01 for both malondialdehyde and 8-hydroxy deoxyguanosine), more severe liver damage (P<0.01) and up-regulated ER stress signal expressions (P<0.01 for GRP78, phos-eIF2alpha1, CHOP, ATF-4, ATF-6, PERK, XBP-1 and pro-caspase-12). All recipients died within 3 days after liver transplantation. Administration of TUDCA or PBA significantly decreased aminotransferase levels (P<0.05), increased superoxide dismutase activities (P<0.01), alleviated liver damage (P<0.01), down-regulated ER stress signal expressions (P<0.01) and improved postoperative survivals (P<0.01). CONCLUSIONS ER stress was involved with DCD liver transplantation in rats. Preoperative intraperitoneally injection of TUDCA or PBA protected ER stress and improved prognosis.
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Knaak JM, Spetzler VN, Goldaracena N, Boehnert MU, Bazerbachi F, Louis KS, Adeyi OA, Minkovich L, Yip PM, Keshavjee S, Levy GA, Grant DR, Selzner N, Selzner M. Subnormothermic ex vivo liver perfusion reduces endothelial cell and bile duct injury after donation after cardiac death pig liver transplantation. Liver Transpl 2014; 20:1296-305. [PMID: 25179693 DOI: 10.1002/lt.23986] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2014] [Revised: 07/18/2014] [Accepted: 08/11/2014] [Indexed: 12/18/2022]
Abstract
An ischemic-type biliary stricture (ITBS) is a common feature after liver transplantation using donation after cardiac death (DCD) grafts. We compared sequential subnormothermic ex vivo liver perfusion (SNEVLP; 33°C) with cold storage (CS) for the prevention of ITBS in DCD liver grafts in pig liver transplantation (n = 5 for each group). Liver grafts were stored for 10 hours at 4°C (CS) or preserved with combined 7-hour CS and 3-hour SNEVLP. Parameters of hepatocyte [aspartate aminotransferase (AST), international normalized ratio (INR), factor V, and caspase 3 immunohistochemistry], endothelial cell (EC; CD31 immunohistochemistry and hyaluronic acid), and biliary injury and function [alkaline phosphatase (ALP), total bilirubin, and bile lactate dehydrogenase (LDH)] were determined. Long-term survival (7 days) after transplantation was similar between the SNEVLP and CS groups (60% versus 40%, P = 0.13). No difference was observed between SNEVLP- and CS-treated animals with respect to the peak of serum INR, factor V, or AST levels within 24 hours. CD31 staining 8 hours after transplantation demonstrated intact EC lining in SNEVLP-treated livers (7.3 × 10(-4) ± 2.6 × 10(-4) cells/μm(2)) but not in CS-treated livers (3.7 × 10(-4) ± 1.3 × 10(-4) cells/μm(2) , P = 0.03). Posttransplant SNEVLP animals had decreased serum ALP and serum bilirubin levels in comparison with CS animals. In addition, LDH in bile fluid was lower in SNEVLP pigs versus CS pigs (14 ± 10 versus 60 ± 18 μmol/L, P = 0.02). Bile duct histology revealed severe bile duct necrosis in 3 of 5 animals in the CS group but none in the SNEVLP group (P = 0.03). Sequential SNEVLP preservation of DCD grafts reduces bile duct and EC injury after liver transplantation.
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Affiliation(s)
- Jan M Knaak
- Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, Toronto, Canada
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Fernández-Simon A, Díaz-Gonzalez A, Thuluvath PJ, Cárdenas A. Endoscopic retrograde cholangiography for biliary anastomotic strictures after liver transplantation. Clin Liver Dis 2014; 18:913-26. [PMID: 25438291 DOI: 10.1016/j.cld.2014.07.009] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Biliary complications after liver transplantation (LT) are an important cause of morbidity and mortality. In most cases, an anastomosis of the bile duct is performed as a duct-to-duct reconstruction, which makes endoscopic therapy with endoscopic retrograde cholangiography (ERC) feasible. Biliary anastomotic strictures (AS) are the most common cause of biliary complications. The early detection of an AS, which can sometimes be challenging given that its clinical presentation is often subtle, is of key importance to obtain high treatment success. In this review, we focus on the management of AS after LT with a special emphasis on ERC.
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Affiliation(s)
- Alejandro Fernández-Simon
- GI/Endoscopy Unit, Institut de Malalties Digestives i Metaboliques, Hospital Clinic, University of Barcelona, Villarroel 170, Esc 3-2, Barcelona 08036, Spain
| | - Alvaro Díaz-Gonzalez
- GI/Endoscopy Unit, Institut de Malalties Digestives i Metaboliques, Hospital Clinic, University of Barcelona, Villarroel 170, Esc 3-2, Barcelona 08036, Spain
| | - Paul J Thuluvath
- Medical Director, Institute for Digestive Health & Liver Disease, Mercy Medical Center, 301 Street, Paul Place, Baltimore, MD 21202, USA
| | - Andrés Cárdenas
- GI/Endoscopy Unit, Institut de Malalties Digestives i Metaboliques, Hospital Clinic, University of Barcelona, Villarroel 170, Esc 3-2, Barcelona 08036, Spain.
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Ruebner RL, Reese PP, Abt PL. Donation after cardiac death liver transplantation is associated with increased risk of end-stage renal disease. Transpl Int 2014; 27:1263-71. [PMID: 25070497 DOI: 10.1111/tri.12409] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2014] [Accepted: 07/20/2014] [Indexed: 12/27/2022]
Abstract
Limited organ supply has led to greater use of liver allografts with higher donor risk indices (DRI) and/or donated after cardiac death (DCD). DCD status is associated with acute kidney injury after liver transplantation; however, less is known about the association between donor quality and end-stage renal disease (ESRD). Using SRTR data, we assembled a cohort of liver transplant recipients from 2/2002 to 12/2010. We fit multivariable Cox regression models for ESRD. Model 1 included total DRI; model 2 included components of DRI, including DCD, as separate variables. Forty thousand four hundred and sixty-three liver transplant recipients were included. Median DRI was 1.40 (IQR 1.14, 1.72); 1822 (5%) received DCD livers. During median follow-up of 3.93 years, ESRD occurred in 2008 (5%) and death in 11 075 (27%) subjects. There was a stepwise increase in ESRD risk with higher DRI (DRI ≥1.14 and <1.40: HR 1.17, P = 0.06; DRI ≥1.40 and <1.72: HR 1.29, P = 0.003; DRI ≥1.72: HR 1.39, P < 0.001, compared with DRI <1.14). Adjusting for DRI components separately, DCD status was most strongly associated with ESRD (HR 1.40, P = 0.008). Higher DRI is associated with ESRD after liver transplantation, driven in part by DCD status. Donor quality is an important predictor of long-term renal outcomes in liver transplant recipients.
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Affiliation(s)
- Rebecca L Ruebner
- Division of Nephrology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA
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Knaak JM, Spetzler VN, Goldaracena N, Louis KS, Selzner N, Selzner M. Technique of subnormothermic ex vivo liver perfusion for the storage, assessment, and repair of marginal liver grafts. J Vis Exp 2014:e51419. [PMID: 25145990 PMCID: PMC4672992 DOI: 10.3791/51419] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
The success of liver transplantation has resulted in a dramatic organ shortage. In most transplant regions 20-30% of patients on the waiting list for liver transplantation die without receiving an organ transplant or are delisted for disease progression. One strategy to increase the donor pool is the utilization of marginal grafts, such as fatty livers, grafts from older donors, or donation after cardiac death (DCD). The current preservation technique of cold static storage is only poorly tolerated by marginal livers resulting in significant organ damage. In addition, cold static organ storage does not allow graft assessment or repair prior to transplantation. These shortcomings of cold static preservation have triggered an interest in warm perfused organ preservation to reduce cold ischemic injury, assess liver grafts during preservation, and explore the opportunity to repair marginal livers prior to transplantation. The optimal pressure and flow conditions, perfusion temperature, composition of the perfusion solution and the need for an oxygen carrier has been controversial in the past. In spite of promising results in several animal studies, the complexity and the costs have prevented a broader clinical application so far. Recently, with enhanced technology and a better understanding of liver physiology during ex vivo perfusion the outcome of warm liver perfusion has improved and consistently good results can be achieved. This paper will provide information about liver retrieval, storage techniques, and isolated liver perfusion in pigs. We will illustrate a) the requirements to ensure sufficient oxygen supply to the organ, b) technical considerations about the perfusion machine and the perfusion solution, and c) biochemical aspects of isolated organs.
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Affiliation(s)
- Jan M Knaak
- Multi Organ Transplant Program, Toronto General Hospital; Department of Surgery, Toronto General Hospital
| | - Vinzent N Spetzler
- Multi Organ Transplant Program, Toronto General Hospital; Department of Surgery, Toronto General Hospital
| | - Nicolas Goldaracena
- Multi Organ Transplant Program, Toronto General Hospital; Department of Surgery, Toronto General Hospital
| | - Kristine S Louis
- Multi Organ Transplant Program, Toronto General Hospital; Department of Surgery, Toronto General Hospital
| | - Nazia Selzner
- Multi Organ Transplant Program, Toronto General Hospital; Department of Medicine, Toronto General Hospital
| | - Markus Selzner
- Multi Organ Transplant Program, Toronto General Hospital; Department of Surgery, Toronto General Hospital;
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Bazerbachi F, Selzner N, Seal JB, Selzner M. Liver transplantation with grafts obtained after cardiac death-current advances in mastering the challenge. World J Transl Med 2014; 3:58-68. [DOI: 10.5528/wjtm.v3.i2.58] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2014] [Revised: 06/11/2014] [Accepted: 07/17/2014] [Indexed: 02/05/2023] Open
Abstract
The scarcity of donor livers has increased the interest in donation after cardiac death (DCD) as an additional pool to expand the availability of organs. However, the initial results of liver transplantation with DCD grafts have been suboptimal due to an increased rate of complications, as well as decreased graft survival. These challenges have led to many developments in DCD donation outcome, as well as basic and translational research. In this article we review the unique characteristics of DCD donors, nuances of DCD organ procurement, the effect of prolonged warm and cold ischemia times, and discuss major studies that compared DCD to donation after brain death liver transplantation, in terms of outcomes and complications. We also review the different methods of donor treatment that has been applied to ameliorate DCD organ outcome, and we discuss the role of machine perfusion techniques in organ reconditioning. We discuss the two major perfusion models, namely, hypothermic machine perfusion and normothermic machine perfusion; we compare both methods, and delineate their major differences.
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Dutkowski P, Schlegel A, de Oliveira M, Müllhaupt B, Neff F, Clavien PA. HOPE for human liver grafts obtained from donors after cardiac death. J Hepatol 2014; 60:765-72. [PMID: 24295869 DOI: 10.1016/j.jhep.2013.11.023] [Citation(s) in RCA: 267] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2013] [Revised: 11/22/2013] [Accepted: 11/23/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Due to ethical rules in most countries, long ischemia times are unavoidable prior to organ procurement of donors without a heartbeat, which can cause early graft failure after liver transplantation or late biliary strictures. Hypothermic oxygenated machine perfusion, used prior to graft implantation, may rescue these high risk organs. METHODS Eight patients with end stage liver diseases received human livers, obtained after controlled cardiac death (Maastricht category III), with a median donor warm ischemia time of 38 min, followed by a standard cold flush and static storage at 4 °C. Hypothermic oxygenated perfusion (HOPE) was applied for 1-2h prior to implantation through the portal vein. The HOPE-perfusate was cooled at 10 °C and oxygenated (pO2 60 kPa) using an ECOPS device (Organ Assist®). Perfusion pressure was maintained below 3 mmHg. RESULTS Each machine perfused liver graft disclosed excellent early function after transplantation. The release of liver enzymes and kidney function, as well as ICU and hospital stays were comparable or better than in matched liver grafts from brain death donors. No evidence of intrahepatic biliary complications could be documented within a median follow up of 8.5 months. CONCLUSIONS This is the first report on cold machine perfusion of human liver grafts obtained after cardiac arrest and subsequent transplantation. Application of HOPE appears well tolerated, easy-to-use, and protective against early and later injuries.
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Affiliation(s)
- Philipp Dutkowski
- Department of Surgery & Transplantation, University Hospital Zurich, Switzerland
| | - Andrea Schlegel
- Department of Surgery & Transplantation, University Hospital Zurich, Switzerland
| | - Michelle de Oliveira
- Department of Surgery & Transplantation, University Hospital Zurich, Switzerland
| | - Beat Müllhaupt
- Department of Hepatology and Gastroenterology, University Hospital Zurich, Switzerland
| | - Fabienne Neff
- Department of Surgery & Transplantation, University Hospital Zurich, Switzerland
| | - Pierre-Alain Clavien
- Department of Surgery & Transplantation, University Hospital Zurich, Switzerland.
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