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Zhixing L, Linsen Y, Peng J, Siyi D, Haoyuan Y, Kun L, Siqi L, Yongwei H, Mingshen Z, Wei L, Hua L, Shuhong Y, Guihua C, Xiao X, Shusen Z, Yang Y. Explainable machine learning for the assessment of donor grafts in liver transplantation. Hepatol Res 2025. [PMID: 40317606 DOI: 10.1111/hepr.14187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 02/16/2025] [Accepted: 03/07/2025] [Indexed: 05/07/2025]
Abstract
BACKGROUND AND AIM The shortage of liver grafts compared to recipients necessitates precise organ assessment. This study aimed to develop a Machine learning (ML) model to predict postoperative delayed graft function (DGF) and visualize the decision-making process for clinical application. METHOD Data from 5242 donor-recipient pairs who underwent liver transplantation (LT) at the top 10 liver transplant centers in China (January 2017 to December 2022) were collected. The dataset was divided into training and validation sets. Sixty-three variables, including demographics, donor characteristics, diagnosis, preoperative lab results, and surgical information were analyzed. The primary outcome was posttransplantation DGF and the second outcome was posttransplantation 1-month and 3-month survival. Recursive feature elimination selected critical variables, and models were built using ML algorithms and logistic regression. Model performance was evaluated by AUC, accuracy, sensitivity, and specificity. The best model was validated with an independent dataset of 394 LT cases (January to June 2023). The SHapley Additive exPlanations package interpreted the top model's decisions. RESULTS Among 5242 cases, 328 (6.26%) developed DGF, with 15 cases (3.81%) in the external validation set. Thirty critical features were selected. The eXtreme Gradient Boosting algorithm achieved the highest AUC (0.877) and accuracy (0.936) in the internal set, and a comparable AUC (0.776) and accuracy (0.957) in the external set. SHAP analysis identified short perfusion time, high donor serum sodium, excessive bleeding during transplantation, high donor γ-glutamyl transpeptidase, and blood glucose levels as top predictors of post-LT DGF. The proposed model AUC's 1-month survival prediction was 0.841 and the 3-month survival prediction was 0.834. CONCLUSIONS The developed model for predicting postoperative DGF demonstrated excellent predictive performance, aiding clinicians in evaluating donor grafts and making informed decisions.
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Affiliation(s)
- Liang Zhixing
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Ye Linsen
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jiang Peng
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Dong Siyi
- National Center for Healthcare Quality Management of Liver Transplant, Hangzhou, China
| | - Yu Haoyuan
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Li Kun
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Li Siqi
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Hu Yongwei
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhang Mingshen
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Liu Wei
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Li Hua
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yi Shuhong
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Chen Guihua
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xu Xiao
- National Center for Healthcare Quality Management of Liver Transplant, Hangzhou, China
- Institute of Translational Medicine, Zhejiang University, Hangzhou, China
- School of Clinical Medicine, Hangzhou Medical College, Hangzhou, China
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, China
| | - Zheng Shusen
- National Center for Healthcare Quality Management of Liver Transplant, Hangzhou, China
- Institute of Translational Medicine, Zhejiang University, Hangzhou, China
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Zhejiang University, Hangzhou, China
- Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital, Hangzhou, China
| | - Yang Yang
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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Calleja R, Rivera M, Guijo-Rubio D, Hessheimer AJ, de la Rosa G, Gastaca M, Otero A, Ramírez P, Boscà-Robledo A, Santoyo J, Marín Gómez LM, Villar Del Moral J, Fundora Y, Lladó L, Loinaz C, Jiménez-Garrido MC, Rodríguez-Laíz G, López-Baena JÁ, Charco R, Varo E, Rotellar F, Alonso A, Rodríguez-Sanjuan JC, Blanco G, Nuño J, Pacheco D, Coll E, Domínguez-Gil B, Fondevila C, Ayllón MD, Durán M, Ciria R, Gutiérrez PA, Gómez-Orellana A, Hervás-Martínez C, Briceño J. Machine Learning Algorithms in Controlled Donation After Circulatory Death Under Normothermic Regional Perfusion: A Graft Survival Prediction Model. Transplantation 2025:00007890-990000000-00970. [PMID: 39780307 DOI: 10.1097/tp.0000000000005312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
Abstract
BACKGROUND Several scores have been developed to stratify the risk of graft loss in controlled donation after circulatory death (cDCD). However, their performance is unsatisfactory in the Spanish population, where most cDCD livers are recovered using normothermic regional perfusion (NRP). Consequently, we explored the role of different machine learning-based classifiers as predictive models for graft survival. A risk stratification score integrated with the model of end-stage liver disease score in a donor-recipient (D-R) matching system was developed. METHODS This retrospective multicenter cohort study used 539 D-R pairs of cDCD livers recovered with NRP, including 20 donor, recipient, and NRP variables. The following machine learning-based classifiers were evaluated: logistic regression, ridge classifier, support vector classifier, multilayer perceptron, and random forest. The endpoints were the 3- and 12-mo graft survival rates. A 3- and 12-mo risk score was developed using the best model obtained. RESULTS Logistic regression yielded the best performance at 3 mo (area under the receiver operating characteristic curve = 0.82) and 12 mo (area under the receiver operating characteristic curve = 0.83). A D-R matching system was proposed on the basis of the current model of end-stage liver disease score and cDCD-NRP risk score. CONCLUSIONS The satisfactory performance of the proposed score within the study population suggests a significant potential to support liver allocation in cDCD-NRP grafts. External validation is challenging, but this methodology may be explored in other regions.
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Affiliation(s)
- Rafael Calleja
- Hepatobiliary Surgery and Liver Transplantation Unit, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Hospital Universitario Reina Sofía, University of Córdoba, Córdoba, Spain
| | - Marcos Rivera
- Department of Computational Sciences and Numerical Analysis, University of Córdoba, Córdoba, Spain
| | - David Guijo-Rubio
- Department of Computational Sciences and Numerical Analysis, University of Córdoba, Córdoba, Spain
| | - Amelia J Hessheimer
- General and Digestive Surgery Department, Hospital Universitario La Paz, Madrid, Spain
| | | | - Mikel Gastaca
- Hepatobiliary Surgery and Liver Transplantation Unit, Biocruces Bizkaia Health Research Institute, Cruces University Hospital, University of the Basque Country, Bilbao, Spain
| | - Alejandra Otero
- General and Digestive Surgery Department, Complejo Hospitalario Universitario de A Coruña, A Coruña, Spain
| | - Pablo Ramírez
- General and Digestive Surgery Department, Hospital Clínico Universitario Virgen de la Arrixaca, IMIB, El Palmar, Spain
| | - Andrea Boscà-Robledo
- General and Digestive Surgery Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain
| | - Julio Santoyo
- General and Digestive Surgery Department, Hospital Regional Universitario de Málaga, Spain
| | - Luis Miguel Marín Gómez
- General and Digestive Surgery Department, Hospital Universitario Virgen del Rocío, Sevilla, Spain
| | - Jesús Villar Del Moral
- General and Digestive Surgery Department, Hospital Universitario Virgen de las Nieves, Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain
| | - Yiliam Fundora
- Division of Hepatobiliary and General Surgery, Department of Surgery, Institut de Malalties Digestives I Metabòliques (IMDiM), Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Laura Lladó
- General and Digestive Surgery Department, Hospital Universitario de Bellvitge, Hospitalet de Llobregat, Spain
| | - Carmelo Loinaz
- General and Digestive Surgery Department, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Manuel C Jiménez-Garrido
- General and Digestive Surgery Department, Hospital Universitario Puerta de Hierro, Majadahonda, Spain
| | - Gonzalo Rodríguez-Laíz
- General and Digestive Surgery Department, Hospital General Universitario de Alicante, Alicante, Spain
| | - José Á López-Baena
- General and Digestive Surgery Department, Hospital General Universitario Gregorio Marañón General University Hospital, Madrid, Spain
| | - Ramón Charco
- General and Digestive Surgery Department, Hospital Universitario Vall d'Hebron, Barcelona, Spain
| | - Evaristo Varo
- General and Digestive Surgery Department, Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain
| | - Fernando Rotellar
- General and Digestive Surgery Department, Hospital Universitario de Navarra, Pamplona, Spain
| | - Ayaya Alonso
- General and Digestive Surgery Department, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
| | - Juan C Rodríguez-Sanjuan
- General and Digestive Surgery Department, Hospital Universitario Marqués de Valdecilla, Santander, Spain
| | - Gerardo Blanco
- General and Digestive Surgery Department, Hospital Universitario Infanta Cristina, Badajoz, Spain
| | - Javier Nuño
- General and Digestive Surgery Department, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - David Pacheco
- General and Digestive Surgery Department, Hospital Universitario Río Hortega, Valladolid, Spain
| | | | | | - Constantino Fondevila
- General and Digestive Surgery Department, Hospital Universitario La Paz, Madrid, Spain
| | - María Dolores Ayllón
- Hepatobiliary Surgery and Liver Transplantation Unit, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Hospital Universitario Reina Sofía, University of Córdoba, Córdoba, Spain
| | - Manuel Durán
- Hepatobiliary Surgery and Liver Transplantation Unit, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Hospital Universitario Reina Sofía, University of Córdoba, Córdoba, Spain
| | - Ruben Ciria
- Hepatobiliary Surgery and Liver Transplantation Unit, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Hospital Universitario Reina Sofía, University of Córdoba, Córdoba, Spain
| | - Pedro A Gutiérrez
- Department of Computational Sciences and Numerical Analysis, University of Córdoba, Córdoba, Spain
| | - Antonio Gómez-Orellana
- Department of Computational Sciences and Numerical Analysis, University of Córdoba, Córdoba, Spain
| | - César Hervás-Martínez
- Department of Computational Sciences and Numerical Analysis, University of Córdoba, Córdoba, Spain
| | - Javier Briceño
- Hepatobiliary Surgery and Liver Transplantation Unit, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Hospital Universitario Reina Sofía, University of Córdoba, Córdoba, Spain
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McLaughlin SD, Amaral JZ, Thomas J, Amaral KZ, Scalzo A. Acute Liver Failure: Is Acetaminophen the Only Culprit? Cureus 2025; 17:e77068. [PMID: 39917094 PMCID: PMC11800727 DOI: 10.7759/cureus.77068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/07/2025] [Indexed: 02/09/2025] Open
Abstract
Epstein-Barr virus (EBV) is a common herpesvirus associated with infectious mononucleosis and rare complications such as hepatitis. EBV-associated hepatitis during acute infection may alter liver metabolism, compounding the risk of drug-induced toxicity. We report the case of a 16-year-old female with acute EBV infection who developed severe acetaminophen toxicity after reported use for migraine relief. Her condition was refractory to N-acetylcysteine but improved with the addition of fomepizole, which may have mitigated liver injury by reducing N-acetyl-p-benzoquinone imine (NAPQI) production via CYP2E1 inhibition and suppressing inflammation. This case underscores the complexity of managing pediatric acute liver failure with coexisting hepatic insults, particularly in the presence of viral infections that disrupt liver metabolism, and highlights fomepizole as a potential adjunct in pediatric N-acetylcysteine-refractory acetaminophen toxicity. Further research is warranted to explore the interactions between viral hepatitis and drug-induced liver injury.
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Affiliation(s)
- Scott D McLaughlin
- Department of Internal Medicine, Advocate Lutheran General Hospital, Park Ridge, USA
| | - Jason Z Amaral
- Department of Orthopedic Surgery, Texas Children's Hospital, Baylor College of Medicine, Houston, USA
| | - Joshua Thomas
- Department of Pediatrics, Sisters of St. Mary (SSM) Health Cardinal Glennon Children's Hospital, Saint Louis University, St. Louis, USA
| | - Keith Z Amaral
- Department of Pediatrics, Summit Healthcare, Show Low, USA
| | - Anthony Scalzo
- Department of Pediatrics, Department of Internal Medicine, Division of Toxicology, Sisters of St. Mary (SSM) Health Cardinal Glennon Children's Hospital, Saint Louis University, St. Louis, USA
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Dehne S, Riede C, Feisst M, Larmann J. In Response. Anesth Analg 2024; 139:e34-e35. [PMID: 39284144 DOI: 10.1213/ane.0000000000007031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/19/2024]
Affiliation(s)
- Sarah Dehne
- Department of Anesthesiology, Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany
| | - Carlo Riede
- Department of Anesthesiology, Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany
| | - Manuel Feisst
- Institute of Medical Biometry, Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany
| | - Jan Larmann
- Department of Anesthesiology, Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany,
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Dehne S, Riede C, Feisst M, Klotz R, Etheredge M, Hölle T, Merle U, Mehrabi A, Michalski CW, Büchler MW, Weigand MA, Larmann J. Tranexamic Acid Administration During Liver Transplantation Is Not Associated With Lower Blood Loss or With Reduced Utilization of Red Blood Cell Transfusion. Anesth Analg 2024; 139:598-608. [PMID: 38236761 DOI: 10.1213/ane.0000000000006804] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/18/2024]
Abstract
BACKGROUND Current clinical guidelines recommend antifibrinolytic treatment for liver transplantation to reduce blood loss and transfusion utilization. However, the clinical relevance of fibrinolysis during liver transplantation is questionable, a benefit of tranexamic acid (TXA) in this context is not supported by sufficient evidence, and adverse effects are also conceivable. Therefore, we tested the hypothesis that use of TXA is associated with reduced blood loss. METHODS We performed a retrospective cohort study on patients who underwent liver transplantation between 2004 and 2017 at Heidelberg University Hospital, Heidelberg, Germany. Univariable and multivariable linear regression analyses were used to determine the association between TXA administration and the primary end point intraoperative blood loss and the secondary end point intra- and postoperative red blood cell (RBC) transfusions. For further secondary outcome analyses, the time to the first occurrence of a composite end point of hepatic artery thrombosis, portal vein thrombosis, and thrombosis of the inferior vena cava were analyzed using a univariable and multivariable Cox proportional hazards model. RESULTS Data from 779 transplantations were included in the final analysis. The median intraoperative blood loss was 3000 mL (1600-5500 mL). Intraoperative TXA administration occurred in 262 patients (33.6%) with an average dose of 1.4 ± 0.7 g and was not associated with intraoperative blood loss (regression coefficient B, -0.020 [-0.051 to 0.012], P = .226) or any of the secondary end points (intraoperative RBC transfusion; regression coefficient B, 0.023 [-0.006 to 0.053], P = .116), postoperative RBC transfusion (regression coefficient B, 0.007 [-0.032 to 0.046], P = .717), and occurrence of thrombosis (hazard ratio [HR], 1.110 [0.903-1.365], P = .321). CONCLUSIONS Our data do not support the use of TXA during liver transplantation. Physicians should exercise caution and consider individual factors when deciding whether or not to administer TXA.
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Affiliation(s)
- Sarah Dehne
- From the Heidelberg University, Medical Faculty Heidelberg, Department of Anesthesiology, Heidelberg, Germany
| | - Carlo Riede
- From the Heidelberg University, Medical Faculty Heidelberg, Department of Anesthesiology, Heidelberg, Germany
| | - Manuel Feisst
- Heidelberg University, Medical Faculty Heidelberg, Institute of Medical Biometry, Heidelberg, Germany
| | - Rosa Klotz
- Heidelberg University, Medical Faculty Heidelberg, Departement of General, Visceral, and Transplantation Surgery, Heidelberg, Germany
| | - Melanie Etheredge
- From the Heidelberg University, Medical Faculty Heidelberg, Department of Anesthesiology, Heidelberg, Germany
| | - Tobias Hölle
- From the Heidelberg University, Medical Faculty Heidelberg, Department of Anesthesiology, Heidelberg, Germany
| | - Uta Merle
- Heidelberg University, Medical Faculty Heidelberg, Department of Internal Medicine IV (Gastroenterology, Infectious Diseases and Intoxications), Heidelberg, Germany
| | - Arianeb Mehrabi
- Heidelberg University, Medical Faculty Heidelberg, Departement of General, Visceral, and Transplantation Surgery, Heidelberg, Germany
| | - Christoph W Michalski
- Heidelberg University, Medical Faculty Heidelberg, Departement of General, Visceral, and Transplantation Surgery, Heidelberg, Germany
| | - Markus W Büchler
- Heidelberg University, Medical Faculty Heidelberg, Departement of General, Visceral, and Transplantation Surgery, Heidelberg, Germany
| | - Markus A Weigand
- From the Heidelberg University, Medical Faculty Heidelberg, Department of Anesthesiology, Heidelberg, Germany
| | - Jan Larmann
- From the Heidelberg University, Medical Faculty Heidelberg, Department of Anesthesiology, Heidelberg, Germany
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Ayyala-Somayajula D, Dodge JL, Zhou K, Terrault NA, Yuan L. The impact of surging transplantation of alcohol-associated liver disease on transplantation for HCC and other indications. Hepatol Commun 2024; 8:e0455. [PMID: 38967588 PMCID: PMC11227353 DOI: 10.1097/hc9.0000000000000455] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Accepted: 04/01/2024] [Indexed: 07/06/2024] Open
Abstract
BACKGROUND Liver transplantation (LT) for alcohol-associated liver disease (ALD) is increasing and may impact LT outcomes for patients listed for HCC and other indications. METHODS Using US adults listed for primary LT (grouped as ALD, HCC, and other) from October 8, 2015, to December 31, 2021, we examined the impact of center-level ALD LT volume (ATxV) on waitlist outcomes in 2 eras: Era 1 (6-month wait for HCC) and Era 2 (MMaT-3). The tertile distribution of ATxV (low to high) was derived from the listed candidates as Tertile 1 (T1): <28.4%, Tertile 2 (T2): 28.4%-37.6%, and Tertile 3 (T3): >37.6% ALD LTs per year. Cumulative incidence of waitlist death and LT within 18 months from listing by LT indication were compared using the Gray test, stratified on eras and ATxV tertiles. Multivariable competing risk regression estimated the adjusted subhazard ratios (sHRs) for the risk of waitlist mortality and LT with interaction effects of ATxV by LT indication (interaction p). RESULTS Of 56,596 candidates listed, the cumulative waitlist mortality for those with HCC and other was higher and their LT probability was lower in high (T3) ATxV centers, compared to low (T1) ATxV centers in Era 2. However, compared to ALD (sHR: 0.92 [0.66-1.26]), the adjusted waitlist mortality for HCC (sHR: 1.15 [0.96-1.38], interaction p = 0.22) and other (sHR: 1.13 [0.87-1.46], interaction p = 0.16) were no different suggesting no differential impact of ATxV on the waitlist mortality. The adjusted LT probability for HCC (sHR: 0.89 [0.72-1.11], interaction p = 0.08) did not differ by AtxV while it was lower for other (sHR: 0.82 [0.67-1.01], interaction p = 0.02) compared to ALD (sHR: 1.04 [0.80-1.34]) suggesting a differential impact of ATxV on LT probability. CONCLUSIONS The high volume of LT for ALD does not impact waitlist mortality for HCC and others but affects LT probability for other in the MMAT-3 era warranting continued monitoring.
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Affiliation(s)
- Divya Ayyala-Somayajula
- Division of Gastrointestinal and Liver Disease, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Jennifer L. Dodge
- Division of Gastrointestinal and Liver Disease, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
- Department of Population and Public Health Sciences, University of Southern California, Los Angeles, California, USA
| | - Kali Zhou
- Division of Gastrointestinal and Liver Disease, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Norah A. Terrault
- Division of Gastrointestinal and Liver Disease, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Liyun Yuan
- Division of Gastrointestinal and Liver Disease, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
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Guo L, Peng P, Peng WT, Zhao J, Wan QQ. Klebsiella pneumoniae infections after liver transplantation: Drug resistance and distribution of pathogens, risk factors, and influence on outcomes. World J Hepatol 2024; 16:612-624. [PMID: 38689752 PMCID: PMC11056902 DOI: 10.4254/wjh.v16.i4.612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Revised: 02/01/2024] [Accepted: 03/08/2024] [Indexed: 04/24/2024] Open
Abstract
BACKGROUND Liver transplantation (LT) is the only curative treatment for end-stage liver disease. However, LT recipients are susceptible to infection, which is the leading cause of early mortality after LT. Klebsiella pneumoniae infections (KPIs) in the bloodstream are common in LT recipients. We hypothesized that KPIs and carbapenem-resistant Klebsiella pneumoniae (CRKP) infections may affect the outcomes of LT recipients. AIM To assess KPI incidence, timing, distribution, drug resistance, and risk factors following LT and its association with outcomes. METHODS This retrospective study included 406 patients undergoing LT at The Third Xiangya Hospital of Central South University, a tertiary hospital, from January 2015 to January 2023. We investigated the risk factors for KPIs and assessed the impact of KPIs and CRKP infections on the prognosis of LT recipients using logistic regression analysis. RESULTS KPI incidence was 7.9% (n = 32), with lung/thoracic cavity the most frequent site of infection; the median time from LT to KPI onset was 7.5 d. Of 44 Klebsiella pneumoniae isolates, 43 (97.7%) and 34 (77.3%) were susceptible to polymyxin B or ceftazidime/avibactam and tigecycline, respectively; > 70% were resistant to piperacillin/ tazobactam, ceftazidime, cefepime, aztreonam, meropenem, and levofloxacin. Female sex [odds ratio (OR) = 2.827, 95% confidence interval (CI): 1.256-6.364; P = 0.012], pre-LT diabetes (OR = 2.794, 95%CI: 1.070-7.294; P = 0.036), day 1 post-LT alanine aminotransferase (ALT) levels ≥ 1500 U/L (OR = 3.645, 95%CI: 1.671-7.950; P = 0.001), and post-LT urethral catheter duration over 4 d (OR = 2.266, 95%CI: 1.016-5.054; P = 0.046) were risk factors for KPI. CRKP infections, but not KPIs, were risk factors for 6-month all-cause mortality post-LT. CONCLUSION KPIs occur frequently and rapidly after LT. Risk factors include female sex, pre-LT diabetes, increased post-LT ALT levels, and urethral catheter duration. CRKP infections, and not KPIs, affect mortality.
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Affiliation(s)
- Long Guo
- Department of Respiratory and Critical Care Medicine, The Third Xiangya Hospital of Central South University, Changsha 410013, Hunan Province, China
| | - Peng Peng
- Clinical Laboratory Medicine Center, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou 421007, Hunan Province, China
| | - Wei-Ting Peng
- The Second Affiliated Hospital Class, Xiangya School of Medicine, Central South University, Changsha 410013, Hunan Province, China
| | - Jie Zhao
- Department of Liver Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China
| | - Qi-Quan Wan
- Department of Transplant Surgery, The Third Xiangya Hospital of Central South University, Changsha 410013, Hunan Province, China
- Engineering and Technology Research Center for Transplantation Medicine of National Health Commission, The Third Xiangya Hospital of Central South University, Changsha 410013, Hunan Province, China.
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Fink MA, Gow PJ, McCaughan GW, Hodgkinson P, Chen J, McCall J, Jaques B, Crawford M, Strasser SI, Hardikar W, Brooke-Smith M, Starkey G, Jeffrey GP, Gane E, Stormon M, Evans H, Tallis C, Byrne AJ, Jones RM. Impact of Share 35 liver transplantation allocation in Australia and New Zealand. Clin Transplant 2024; 38:e15203. [PMID: 38088459 DOI: 10.1111/ctr.15203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 10/30/2023] [Accepted: 11/19/2023] [Indexed: 01/31/2024]
Abstract
Patients with high model for end-stage liver disease (MELD) scores waiting for liver transplantation in Australia and New Zealand (ANZ) have had limited access to deceased donor livers and therefore binational sharing of livers, for patients with a MELD score ≥35 was introduced in February 2016. Waiting list mortality, post-transplant outcomes and intention-to-treat survival were compared between patients whose MELD score reached 35 on the waiting list between October 2013 and April 2015 (Pre-Share 35 group, n = 23) and patients who were Share 35 listed between February 2016 and May 2022 (Share 35 group, n = 112). There was significantly reduced waiting list mortality in share 35 listed patients in comparison to the pre-Share 35 group (11.7% vs. 52.2%, OR .120 95% CI .044-.328, P < .001). Post-transplant patient and graft survival were not significantly different between the groups (5-year patient survival 82% vs. 84%, P = .991, 5-year graft survival 82% vs. 76%, P = .543). Intention-to-treat survival was superior in the Share 35 group (HR .302, 95% CI .149-.614, P < .001). Introduction of Share 35 in ANZ resulted in a 78% risk reduction in waiting list mortality, equivalent post-transplant survival and an improvement in intention-to-treat survival.
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Affiliation(s)
- Michael A Fink
- Department of Surgery, Austin Health, The University of Melbourne, Melbourne, Victoria, Australia
- Victorian Liver Transplant Unit, Austin Health, Melbourne, Victoria, Australia
- Australia and New Zealand Liver and Intestinal Transplant Registry, Melbourne, Australia
| | - Paul J Gow
- Victorian Liver Transplant Unit, Austin Health, Melbourne, Victoria, Australia
| | - Geoffrey W McCaughan
- University of Sydney, Sydney, New South Wales, Australia
- Liver Injury and Cancer, Centenary Institute, Camperdown, New South Wales, Australia
- Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Sydney, Australia
| | - Peter Hodgkinson
- Queensland Liver Transplant Service, Princess Alexandra Hospital and Queensland Children's Hospital, Brisbane, Australia
| | - John Chen
- Flinders Medical Centre, Adelaide, South Australia, Australia
| | - John McCall
- University of Auckland, Auckland, New Zealand
- New Zealand Liver Transplant Service, Auckland City Hospital, Auckland, New Zealand
| | - Bryon Jaques
- Western Australian Liver Transplant Unit, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia
| | - Michael Crawford
- University of Sydney, Sydney, New South Wales, Australia
- Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Sydney, Australia
| | - Simone I Strasser
- University of Sydney, Sydney, New South Wales, Australia
- Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Sydney, Australia
| | - Winita Hardikar
- Gastroenterology and Clinical Nutrition Department Royal Children's Hospital, Melbourne, Victoria, Australia
| | | | - Graham Starkey
- Victorian Liver Transplant Unit, Austin Health, Melbourne, Victoria, Australia
| | - Gary P Jeffrey
- Western Australian Liver Transplant Unit, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia
- Medical School, The University of Western Australia, Perth, Western Australia, Australia
| | - Ed Gane
- University of Auckland, Auckland, New Zealand
- New Zealand Liver Transplant Service, Auckland City Hospital, Auckland, New Zealand
| | - Michael Stormon
- University of Sydney, Sydney, New South Wales, Australia
- Australian National Liver Transplantation Service, Children's Hospital at Westmead, Sydney, New South Wales, Australia
| | - Helen Evans
- University of Auckland, Auckland, New Zealand
- Department of Paediatric Gastroenterology, Starship Child Health, Auckland, New Zealand
| | - Caroline Tallis
- Queensland Liver Transplant Service, Princess Alexandra Hospital and Queensland Children's Hospital, Brisbane, Australia
| | - Amanda J Byrne
- Australia and New Zealand Liver and Intestinal Transplant Registry, Melbourne, Australia
| | - Robert M Jones
- Department of Surgery, Austin Health, The University of Melbourne, Melbourne, Victoria, Australia
- Victorian Liver Transplant Unit, Austin Health, Melbourne, Victoria, Australia
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9
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Abdelrahim M, Esmail A, Abudayyeh A, Murakami N, Victor D, Kodali S, Cheah YL, Simon CJ, Noureddin M, Connor A, Saharia A, Moore LW, Heyne K, Kaseb AO, Gaber AO, Ghobrial RM. Transplant Oncology: An Emerging Discipline of Cancer Treatment. Cancers (Basel) 2023; 15:5337. [PMID: 38001597 PMCID: PMC10670243 DOI: 10.3390/cancers15225337] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 10/30/2023] [Indexed: 11/26/2023] Open
Abstract
Transplant oncology is an emerging concept of cancer treatment with a promising prospective outcome. The applications of oncology, transplant medicine, and surgery are the core of transplant oncology to improve patients' survival and quality of life. The main concept of transplant oncology is to radically cure cancer by removing the diseased organ and replacing it with a healthy one, aiming to improve the survival outcomes and quality of life of cancer patients. Subsequently, it seeks to expand the treatment options and research for hepatobiliary malignancies, which have seen significantly improved survival outcomes after the implementation of liver transplantation (LT). In the case of colorectal cancer (CRC) in the transplant setting, where the liver is the most common site of metastasis of patients who are considered to have unresectable disease, initial studies have shown improved survival for LT treatment compared to palliative therapy interventions. The indications of LT for hepatobiliary malignancies have been slowly expanded over the years beyond Milan criteria in a stepwise manner. However, the outcome improvements and overall patient survival are limited to the specifics of the setting and systematic intervention options. This review aims to illustrate the representative concepts and history of transplant oncology as an emerging discipline for the management of hepatobiliary malignancies, in addition to other emerging concepts, such as the uses of immunotherapy in a peri-transplant setting as well as the use of circulating tumor DNA (ctDNA) for surveillance post-transplantation.
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Affiliation(s)
- Maen Abdelrahim
- Section of GI Oncology, Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX 77030, USA; (A.E.)
- Cockrell Center of Advanced Therapeutics Phase I Program, Houston Methodist Research Institute, Houston, TX 77030, USA
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
| | - Abdullah Esmail
- Section of GI Oncology, Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX 77030, USA; (A.E.)
| | - Ala Abudayyeh
- Section of Nephrology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Naoka Murakami
- Division of Renal Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA;
| | - David Victor
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Sudha Kodali
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Yee Lee Cheah
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Caroline J. Simon
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Mazen Noureddin
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Ashton Connor
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Ashish Saharia
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Linda W. Moore
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Kirk Heyne
- Section of GI Oncology, Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX 77030, USA; (A.E.)
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
| | - Ahmed O. Kaseb
- Department of Gastrointestinal (GI) Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - A. Osama Gaber
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Rafik Mark Ghobrial
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
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10
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Todeschini L, Cristin L, Martinino A, Mattia A, Agnes S, Giovinazzo F. The Role of mTOR Inhibitors after Liver Transplantation for Hepatocellular Carcinoma. Curr Oncol 2023; 30:5574-5592. [PMID: 37366904 DOI: 10.3390/curroncol30060421] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 06/06/2023] [Accepted: 06/07/2023] [Indexed: 06/28/2023] Open
Abstract
Liver transplantation is a treatment option for nonresectable patients with early-stage HCC, with more significant advantages when Milan criteria are fulfilled. An immunosuppressive regimen is required to reduce the risk of graft rejection after transplantation, and CNIs represent the drugs of choice in this setting. However, their inhibitory effect on T-cell activity accounts for a higher risk of tumour regrowth. mTOR inhibitors (mTORi) have been introduced as an alternative immunosuppressive approach to conventional CNI-based regimens to address both immunosuppression and cancer control. The PI3K-AKT-mTOR signalling pathway regulates protein translation, cell growth, and metabolism, and the pathway is frequently deregulated in human tumours. Several studies have suggested the role of mTORi in reducing HCC progression after LT, accounting for a lower recurrence rate. Furthermore, mTOR immunosuppression controls the renal damage associated with CNI exposure. Conversion to mTOR inhibitors is associated with stabilizing and recovering renal dysfunction, suggesting an essential renoprotective effect. Limitations in this therapeutic approach are related to their negative impact on lipid and glucose metabolism as well as on proteinuria development and wound healing. This review aims to summarize the roles of mTORi in managing patients with HCC undergoing LT. Strategies to overcome common adverse effects are also proposed.
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Affiliation(s)
- Letizia Todeschini
- Faculty of Medicine and Surgery, University of Verona, 37134 Verona, Italy
| | - Luca Cristin
- Faculty of Medicine and Surgery, University of Verona, 37134 Verona, Italy
| | | | - Amelia Mattia
- General Surgery and Liver Transplantation Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Salvatore Agnes
- General Surgery and Liver Transplantation Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Francesco Giovinazzo
- General Surgery and Liver Transplantation Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
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11
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Fonseca LG, Chen AT, de Oliveira IS, Chagas AL, Kruger JA, Carrilho FJ. Brazilian Landscape of Hepatocellular Carcinoma. JCO Glob Oncol 2023; 9:e2200416. [PMID: 37348031 PMCID: PMC10497258 DOI: 10.1200/go.22.00416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 03/28/2023] [Accepted: 04/25/2023] [Indexed: 06/24/2023] Open
Abstract
The incidence of hepatocellular carcinoma (HCC) is expected to increase in the coming years, and strategies to mitigate the burden of this disease are needed in different regions. Geographic variations in epidemiology and risk factors, such as viral hepatitis and metabolic disease, pose challenges in adopting programs for early detection programs and management of patients with HCC. Brazil, like other countries, has high economic and social inequality, with heterogeneous access to health care. Viral hepatitis is the main risk factor but there is growing awareness of fatty liver disease. Risk factor monitoring and screening programs are unmet priorities because patients are often diagnosed at later stages. Advances in the management of patients with HCC have been made in recent years, including new tools for selecting patients for liver transplantation, sophisticated surgical techniques, and new systemic agents. High-volume academic centers often achieve favorable results through the adoption and application of established treatments, but this is not a reality in most regions of Brazil, because of disparities in wealth and resources. As HCC management requires a coordinated and multidisciplinary team, the role of local referral centers in decentralizing access to treatments and promoting health education in different regions should be encouraged and supported.
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Affiliation(s)
- Leonardo G. Fonseca
- Medical Oncology, Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, University of São Paulo, School of Medicine, São Paulo, Brazil
| | - Andre T.C. Chen
- Department of Radiation Oncology, Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, University of São Paulo, School of Medicine, São Paulo, Brazil
| | - Irai S. de Oliveira
- Department of Radiology, Hospital das Clínicas, University of São Paulo, School of Medicine, São Paulo, Brazil
| | - Aline L. Chagas
- Department of Gastroenterology, Division of Clinical Gastroenterology and Hepatology, Hospital das Clínicas, University of São Paulo School of Medicine, São Paulo, Brazil
- Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Jaime A.P. Kruger
- Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Flair J. Carrilho
- Department of Gastroenterology, Division of Clinical Gastroenterology and Hepatology, Hospital das Clínicas, University of São Paulo School of Medicine, São Paulo, Brazil
- Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, University of São Paulo School of Medicine, São Paulo, Brazil
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12
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Lubell TR, Cruz AT, Tanverdi MS, Ochs JB, Lobritto S, Saini S, Mavrogiorgos E, Dayan PS. Bacteremia in Pediatric Liver Transplant Recipients. Pediatr Infect Dis J 2023:00006454-990000000-00437. [PMID: 37171971 DOI: 10.1097/inf.0000000000003957] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/14/2023]
Abstract
BACKGROUND We aimed to determine the frequency of bacteremia, septic shock and bacterial meningitis in pediatric liver transplant recipients (pLTRs) in the outpatient setting and to identify clinical factors associated with bacteremia. METHODS Multicenter retrospective study of pLTRs evaluated in the emergency department or outpatient clinic between 2010 and 2018 for suspected infection, defined as fever ≥38 °C or a blood culture obtained. We excluded patients with nontransplant immunodeficiency, multiorgan transplants or intestinal failure. The primary outcome was bacteremia; secondary outcomes included fluid-refractory septic shock, bacterial meningitis and antibiotic resistance. The unit of analysis was the encounter. RESULTS A total of 151 children had 336 encounters for infection evaluation within 2 years of transplant. Of 307 (91.4%) encounters with blood cultures, 17 (5.5%) had bacteremia, with 10 (58.8%) occurring within 3 months of transplant. Fluid-refractory septic shock and bacterial meningitis occurred in 7 out of 307 (2.8%) and 0 out of 307 encounters, respectively. Factors associated with bacteremia included closer proximity to transplant (<3 months) [odds ratio (OR): 3.6; 95% confidence interval (CI): 1.3-9.8; P = 0.01], shorter duration of illness (OR: 4.3; 95% CI: 1.5-12.0; P < 0.01) and the presence of a central venous catheter (CVC) (OR: 12.7; 95% CI: 4.4-36.6; P < 0.01). However, 5 (29.4%) encounters with bacteremia had none of these factors. Among Gram-positive pathogens, 1 out of 7 (14.2%) isolates were resistant to vancomycin. Among Gram-negative pathogens, 3 out of 13 (23.1%) isolates were resistant to 3rd generation cephalosporins. CONCLUSIONS Bacteremia was an important cause of infection within 2 years of pLTR. Clinical factors increased the risk of bacteremia. Further, large sample studies should derive multivariable models to identify those at high and low risk of bacteremia to optimize antibiotic use.
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Affiliation(s)
- Tamar R Lubell
- From the Division of Pediatric Emergency Medicine, Department of Emergency Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York
| | - Andrea T Cruz
- Divisions of Emergency Medicine & Infectious Diseases, Department of Pediatrics, Baylor College of Medicine, Houston, Texas
| | - Melisa S Tanverdi
- Section of Pediatric Emergency Medicine, Department of Pediatrics, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado
| | - Julie B Ochs
- New York Institute of Technology College of Osteopathic Medicine, Old Westbury, New York
| | - Steven Lobritto
- Divisions of Pediatric Gastroenterology and Transplant Hepatology, Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University, New York
| | | | | | - Peter S Dayan
- From the Division of Pediatric Emergency Medicine, Department of Emergency Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York
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13
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Alnagar AM, Hakeem AR, Daradka K, Kyrana E, Methga M, Palaniswamy K, Rajwal S, Mulla J, O'meara M, Upasani V, Vijayanand D, Prasad R, Attia MS. Long-term outcomes of pediatric liver transplantation in acute liver failure vs end-stage chronic liver disease: A retrospective observational study. World J Transplant 2023; 13:96-106. [PMID: 36968135 PMCID: PMC10037232 DOI: 10.5500/wjt.v13.i3.96] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Revised: 12/22/2022] [Accepted: 03/06/2023] [Indexed: 03/16/2023] Open
Abstract
BACKGROUND Children with acute liver failure (ALF) who meet the criteria are eligible for super-urgent transplantation, whereas children with end-stage chronic liver disease (ESCLD) are usually transplanted electively. Pediatric liver transplantation (PLT) in ALF and ESCLD settings has been well described in the literature, but there are no studies comparing the outcomes in these two groups.
AIM To determine if there is a difference in post-operative complications and survival outcomes between ALF and ESCLD in PLT.
METHODS This was a retrospective observational study of all primary PLTs performed at a single center between 2000 and 2019. ALF and ESCLD groups were compared for pretransplant recipient, donor and operative parameters, and post-operative outcomes including graft and patient survival.
RESULTS Over a 20-year study period, 232 primary PLTs were performed at our center; 195 were transplanted for ESCLD and 37 were transplanted for ALF. The ALF recipients were significantly older (median 8 years vs 5.4 years; P = 0.031) and heavier (31 kg vs 21 kg; P = 0.011). Living donor grafts were used more in the ESCLD group (34 vs 0; P = 0.006). There was no difference between the two groups concerning vascular complications and rejection, but there were more bile leaks in the ESCLD group. Post-transplant patient survival was significantly higher in the ESCLD group: 1-, 5-, and 10-year survival rates were 97.9%, 93.9%, and 89.4%, respectively, compared to 78.3%, 78.3%, and 78.3% in the ALF group (P = 0.007). However, there was no difference in 1-, 5-, and 10-year graft survival between the ESCLD and ALF groups (90.7%, 82.9%, 77.3% vs 75.6%, 72.4%, and 66.9%; P = 0.119).
CONCLUSION Patient survival is inferior in ALF compared to ESCLD recipients; the main reason is death in the 1st year post-PLT in ALF group. Once the ALF children overcome the 1st year after transplant, their survival stabilizes, and they have good long-term outcomes.
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Affiliation(s)
- Amr M Alnagar
- Department of General Surgery, Faculty of Medicine, Alexandria University, Alexandria 21615, Egypt
- Liver and Transplant Surgery, The Leeds Teaching Hospitals, NHS Foundation Trust, Leeds LS9 7TF, United Kingdom
| | - Abdul R Hakeem
- Liver and Transplant Surgery, The Leeds Teaching Hospitals, NHS Foundation Trust, Leeds LS9 7TF, United Kingdom
| | - Khaled Daradka
- Liver and Transplant Surgery, The Leeds Teaching Hospitals, NHS Foundation Trust, Leeds LS9 7TF, United Kingdom
| | - Eirini Kyrana
- Liver and Transplant Surgery, The Leeds Teaching Hospitals, NHS Foundation Trust, Leeds LS9 7TF, United Kingdom
| | - Marumbo Methga
- Liver and Transplant Surgery, The Leeds Teaching Hospitals, NHS Foundation Trust, Leeds LS9 7TF, United Kingdom
| | - Karthikeyan Palaniswamy
- Liver and Transplant Surgery, The Leeds Teaching Hospitals, NHS Foundation Trust, Leeds LS9 7TF, United Kingdom
| | - Sanjay Rajwal
- Liver and Transplant Surgery, The Leeds Teaching Hospitals, NHS Foundation Trust, Leeds LS9 7TF, United Kingdom
| | - Jamila Mulla
- Liver and Transplant Surgery, The Leeds Teaching Hospitals, NHS Foundation Trust, Leeds LS9 7TF, United Kingdom
| | - Moira O'meara
- Liver and Transplant Surgery, The Leeds Teaching Hospitals, NHS Foundation Trust, Leeds LS9 7TF, United Kingdom
| | - Vivek Upasani
- Liver and Transplant Surgery, The Leeds Teaching Hospitals, NHS Foundation Trust, Leeds LS9 7TF, United Kingdom
| | - Dhakshinamoorthy Vijayanand
- Liver and Transplant Surgery, The Leeds Teaching Hospitals, NHS Foundation Trust, Leeds LS9 7TF, United Kingdom
| | - Raj Prasad
- Liver and Transplant Surgery, The Leeds Teaching Hospitals, NHS Foundation Trust, Leeds LS9 7TF, United Kingdom
| | - Magdy S Attia
- Liver and Transplant Surgery, The Leeds Teaching Hospitals, NHS Foundation Trust, Leeds LS9 7TF, United Kingdom
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14
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Yong JN, Lim WH, Ng CH, Tan DJH, Xiao J, Tay PWL, Lin SY, Syn N, Chew N, Nah B, Dan YY, Huang DQ, Tan EXX, Sanyal AJ, Noureddin M, Siddiqui MS, Muthiah MD. Outcomes of Nonalcoholic Steatohepatitis After Liver Transplantation: An Updated Meta-Analysis and Systematic Review. Clin Gastroenterol Hepatol 2023; 21:45-54.e6. [PMID: 34801743 DOI: 10.1016/j.cgh.2021.11.014] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 11/05/2021] [Accepted: 11/10/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Nonalcoholic steatohepatitis (NASH) is the fastest growing indication of liver transplantation (LT) and is projected to be the leading cause of LT in the near future. The systemic pathogenesis of NASH increases risks of adverse clinical outcomes in patients with NASH receiving LT. Thus, this study aimed to conduct a time-dependent survival analysis between LT recipients with and without NASH using hazard ratios. METHODS A search was conducted on Medline and Embase databases for articles relating to LT outcomes for NASH recipients. A survival analysis was conducted of hazard ratios using the DerSimonian and Laird random-effects model with meta-regression. To account for censoring, survival data were reconstructed from published Kaplan-Meier curves and pooled to derive more accurate hazard estimates and all-cause mortality in NASH patients after LT. Pairwise meta-analysis was conducted to analyze secondary outcomes. RESULTS Fifteen studies involving 119,327 LT recipients were included in our analysis with a prevalence of NASH of 20.2% (95% CI, 12.9-30.2). The pooled 1-year, 5-year, and 10-year all-cause mortality in NASH patients after LT were 12.5%, 24.4%, and 37.9%, respectively. Overall survival was comparable between LT recipients for NASH vs non-NASH (hazard ratio, 0.910; 95% CI, 0.760 to 1.10; P = .34). Meta-regression showed that a higher model for end-stage liver disease score was associated with significantly worse overall survival in NASH compared with non-NASH after LT (95% CI, -0.0856 to -0.0181; P = .0026). CONCLUSIONS This study shows that patients undergoing LT for NASH cirrhosis have comparable complication rates, overall survival, and graft survival compared with non-NASH patients, although close monitoring may be indicated for those with higher model for end-stage liver disease scores.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Nicholas Chew
- Department of Cardiology, National University Heart Centre
| | - Benjamin Nah
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Yock Young Dan
- Yong Loo Lin School of Medicine; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore; Cancer Science Institute of Singapore, National University of Singapore, Singapore
| | - Daniel Q Huang
- Yong Loo Lin School of Medicine; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Eunice Xiang Xuan Tan
- Yong Loo Lin School of Medicine; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Arun J Sanyal
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia
| | - Mazen Noureddin
- Cedars-Sinai Fatty Liver Program, Division of Digestive and Liver Diseases, Department of Medicine, Comprehensive Transplant Center, Cedars-Sinai Medical Centre, Los Angeles, California
| | - Mohammad Shadab Siddiqui
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia
| | - Mark D Muthiah
- Yong Loo Lin School of Medicine; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore.
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15
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Kulkarni SS, Goss CW, Khan AS, Nadler ML, Stoll JM, Doyle MB, Turmelle YP, Rudnick DA. Outcomes Analyses of Pediatric Acute Liver Failure Subjects Listed for Liver Transplantation. J Pediatr Gastroenterol Nutr 2022; 74:750-756. [PMID: 35442235 PMCID: PMC9296584 DOI: 10.1097/mpg.0000000000003448] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND We characterized recent outcomes in US pediatric acute liver failure (PALF) subjects listed for liver transplantation (LT) using the Scientific Registry of Transplant Recipients (SRTR) database. METHODS Pediatric subjects listed for LT from 2002 to 2015 were assigned to the "PALF" group based on status 1/1A listing, INR >2, no hepatic artery thrombosis, and no primary graft nonfunction (N = 397). Subjects were assigned to the "non-PALF" group if listed with any status other than 1/1A (N = 4509). RESULTS The PALF group had more infants <3 months of age and males at listing for LT compared to the non-PALF group. Two-thirds of PALF subjects had an indeterminate etiology. LT waitlist survival was significantly worse in the PALF group compared to the non-PALF group. Likelihood of removal from the LT waitlist for being "too sick" was higher, while that of removal for "spontaneous recovery" was lower in PALF subjects. Post-LT short-term (30 days) and long-term (60 months) outcomes were also significantly worse in PALF versus non-PALF subjects. PALF subjects who underwent living-donor-liver-transplant (LDLT) had similar LT waitlist times and post-LT survival compared to those undergoing deceased-donor-liver-transplant (DDLT). Over the study period, we observed a decreased number of liver transplants, and increase in LT waitlist- and short-term post-LT-survival in PALF subjects. CONCLUSION LT waitlist and post-LT outcomes are worse in PALF subjects compared to non-PALF subjects. PALF subjects who undergo LDLT have similar waitlist times and post-LT outcomes compared to those undergoing DDLT.
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Affiliation(s)
- Sakil S. Kulkarni
- Department of Pediatrics, Washington University in St. Louis, St. Louis Children’s Hospital, St. Louis, MO, U.S.A
| | - Charles W. Goss
- Department of Biostatistics, Washington University in St. Louis, St. Louis, MO, U.S.A
| | - Adeel S. Khan
- Department of Surgery, Washington University in St. Louis, Barnes Jewish Hospital, St. Louis, MO, U.S.A
| | - Michelle L. Nadler
- Department of Pediatrics, Washington University in St. Louis, St. Louis Children’s Hospital, St. Louis, MO, U.S.A
| | - Janis M. Stoll
- Department of Pediatrics, Washington University in St. Louis, St. Louis Children’s Hospital, St. Louis, MO, U.S.A
| | - Maria B. Doyle
- Department of Surgery, Washington University in St. Louis, Barnes Jewish Hospital, St. Louis, MO, U.S.A
| | - Yumirle P. Turmelle
- Department of Pediatrics, Washington University in St. Louis, St. Louis Children’s Hospital, St. Louis, MO, U.S.A
| | - David A. Rudnick
- Department of Pediatrics, Washington University in St. Louis, St. Louis Children’s Hospital, St. Louis, MO, U.S.A
- Department of Developmental Biology, Washington University in St. Louis, St. Louis Children’s Hospital, St. Louis, MO, U.S.A
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Jagadisan B, Dhawan A. Emergencies in paediatric hepatology. J Hepatol 2022; 76:1199-1214. [PMID: 34990749 DOI: 10.1016/j.jhep.2021.12.027] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 12/17/2021] [Accepted: 12/21/2021] [Indexed: 12/12/2022]
Abstract
The aetiology of several liver diseases in children is age specific and many of these conditions have significant and potentially long-term clinical repercussions if not diagnosed early and managed in a timely fashion. We address 5 clinical scenarios that cover most of the diagnostic and therapeutic emergencies in children: infants with liver disease; acute liver failure; management of bleeding varices; liver-based metabolic disorders; and liver tumours and trauma. A wide spectrum of conditions that cause liver disease in infants may present as conjugated jaundice, which could be the only symptom of time-sensitive disorders - such as biliary atresia, metabolic disorders, infections, and haematological/alloimmune disorders - wherein algorithmic multistage testing is required for accurate diagnosis. In infantile cholestasis, algorithmic multistage tests are necessary for an accurate early diagnosis, while vitamin K, specific milk formulae and disease-specific medications are essential to avoid mortality and long-term morbidity. Management of paediatric acute liver failure requires co-ordination with a liver transplant centre, safe transport and detailed age-specific aetiological work-up - clinical stabilisation with appropriate supportive care is central to survival if transplantation is indicated. Gastrointestinal bleeding may present as the initial manifestation or during follow-up in patients with portal vein thrombosis or chronic liver disease and can be managed pharmacologically, or with endoscopic/radiological interventions. Liver-based inborn errors of metabolism may present as encephalopathy that needs to be recognised and treated early to avoid further neurological sequelae and death. Liver tumours and liver trauma are both rare occurrences in children and are best managed by a multidisciplinary team in a specialist centre.
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Affiliation(s)
- Barath Jagadisan
- Pediatric Liver GI and Nutrition Centre and MowatLabs, King's College Hospital, London, UK
| | - Anil Dhawan
- Pediatric Liver GI and Nutrition Centre and MowatLabs, King's College Hospital, London, UK.
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17
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Kim M, Hwang S, Ahn CS, Moon DB, Ha TY, Song GW, Jung DH, Park GC, Kim KH, Namgoong JM, Kang WH, Yoon YI, Cho HD, Na BG, Kim SH, Lee SG. Twenty-year longitudinal follow-up after liver transplantation: a single-center experience with 251 consecutive patients. KOREAN JOURNAL OF TRANSPLANTATION 2022; 36:45-53. [PMID: 35769427 PMCID: PMC9235526 DOI: 10.4285/kjt.21.0031] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 01/20/2022] [Accepted: 02/08/2022] [Indexed: 11/13/2022] Open
Abstract
Background The outcomes of liver transplantation (LT) have improved, but actual 20-year survival data have rarely been presented. Methods Longitudinal follow-up data of 20-year LT survivors were retrospectively analyzed. The LT database of our institution was searched to identify patients who underwent primary LT from January 2000 to December 2001. The study cohort of 251 patients was divided into three groups 207 adults who underwent living donor LT (LDLT), 22 adults who underwent deceased donor LT (DDLT), and 22 pediatric patients who underwent LT. Results Hepatitis B virus-associated liver cirrhosis and biliary atresia were the most common indications for adult and pediatric LT, respectively. Seven patients required retransplantation, including six who underwent DDLT and one who underwent LDLT. Twenty-two patients died within 3 months after LT and 69 died at later intervals. The overall survival rates at 1, 3, 5, 10, and 20 years were 86.4%, 79.6%, 77.7%, 72.8%, and 62.6%, respectively, in the adult LDLT group; 86.4%, 72.7%, 72.7%, 72.7%, and 68.2%, respectively, in the adult DDLT group; and 86.4%, 86.4%, 81.8%, 81.8%, and 77.3%, respectively, in the pediatric LT group (P=0.545). Common immunosuppressive regimens at 20 years included tacrolimus monotherapy, tacrolimus-mycophenolate dual therapy, cyclosporine monotherapy, and mycophenolate monotherapy. Conclusions The present study is the first report of actual 20-year survival data from a Korean high-volume LT center. The graft and patient survival outcomes reflected the early experiences of LT in our institution, with long-term outcomes being similar regardless of graft type and patient age.
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Affiliation(s)
- Minjae Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Shin Hwang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chul-Soo Ahn
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Deok-Bog Moon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Tae-Yong Ha
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gi-Won Song
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dong-Hwan Jung
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gil-Chun Park
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ki-Hun Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jung-Man Namgoong
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Woo-Hyoung Kang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young-In Yoon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hwui-Dong Cho
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Byeong-Gon Na
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sang Hoon Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung-Gyu Lee
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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18
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Ginanni Corradini S, Ferri F. Referral to the Liver Transplant Center. TEXTBOOK OF LIVER TRANSPLANTATION 2022:597-611. [DOI: 10.1007/978-3-030-82930-8_35] [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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19
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Khayat A, Vitola B. Prevalence and Clinical Significance of Autoantibodies in Children with Overweight and Obesity with Nonalcoholic Fatty Liver Disease. J Pediatr 2021; 239:155-160. [PMID: 34454951 DOI: 10.1016/j.jpeds.2021.08.041] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 08/19/2021] [Accepted: 08/20/2021] [Indexed: 12/18/2022]
Abstract
OBJECTIVES To evaluate the prevalence and clinical significance of autoantibodies in children with overweight and obesity with nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) compared with those with autoimmune liver disease (ALD). STUDY DESIGN This was a retrospective, cross-sectional study of children with a biopsy-proven diagnosis of NAFL, NASH, autoimmune hepatitis (AIH), or primary sclerosing cholangitis (PSC) and a body mass index (BMI) >85th percentile treated between 2007 and 2016. RESULTS A total of 181 patients were identified, including 31 (17%) with NAFL, 121 (67%) with NASH, 12 (6.6%) with ALD (AIH, PSC, or overlap), and 17 (9.4%) with combined ALD and NAFLD. Antinuclear antibody (ANA), anti-actin antibody, and anti-liver kidney microsomal (LKM) antibody were positive in 16.1%, 13.8%, and 0%, respectively, of the patients with NAFL and in 32.8%, 15.5%, and 0%, respectively, of those with NASH. Total immunoglobulin G (IgG) was elevated in 27.3% of the patients with NAFL and in 47.7% of those with NASH, but in 100% of those with ALD. The positive predictive value of LKM was 100% for ALD but only 29% for ANA and 46% for anti-actin antibody. CONCLUSIONS False-positive rates of autoantibodies were higher in pediatric patients with overweight and obesity with NAFLD compared with the general adult population. Positive LKM had the highest specificity and positive predictive value, and elevated IgG level had the highest sensitivity for ALD. The presence of autoantibodies does not signal more severe NAFLD in children. BMI >98th percentile seems to be an important breakpoint above which ALD is less likely.
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Affiliation(s)
- Ammar Khayat
- Department of Pediatrics, Umm Al Qura University, Al Abdeyah, Makkah, Saudi Arabia; Division of Pediatric Gastroenterology, Hepatology and Nutrition, Medical College of Wisconsin, Milwaukee, WI
| | - Bernadette Vitola
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Medical College of Wisconsin, Milwaukee, WI.
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20
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Chen YY, Li H, Xu BY, Zheng X, Li BL, Wang XB, Huang Y, Gao YH, Qian ZP, Liu F, Lu XB, Shang J, Li H, Wang SY, Zhang YH, Meng ZJ. Plasma Exchange-Based Non-bioartificial Liver Support System Improves the Short-Term Outcomes of Patients With Hepatitis B Virus-Associated Acute-on-Chronic Liver Failure: A Multicenter Prospective Cohort Study. Front Med (Lausanne) 2021; 8:779744. [PMID: 34869500 PMCID: PMC8635207 DOI: 10.3389/fmed.2021.779744] [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: 09/19/2021] [Accepted: 10/13/2021] [Indexed: 11/13/2022] Open
Abstract
Background and aims: Hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) is a complicated syndrome with extremely high short-term mortality. Whether plasma exchange (PE) improves HBV-ACLF outcomes remains controversial. Here, PE-based non-bioartificial liver support system (NB-ALSS) effects on short-term HBV-ACLF patient outcomes were investigated. Materials and methods: HBV-ACLF patients from Chinese Acute-on-chronic Liver Failure (CATCH-LIFE) cohort receiving standard medical therapy (SMT) alone or PE-based NB-ALSS in addition to SMT were allocated to SMT and SMT+PE groups, respectively; propensity score matching (PSM) was used to eliminate confounding bias. Short-term (28/90-day and 1-year) survival rates were calculated (Kaplan-Meier). Results: In total, 524 patients with HBV-ACLF were enrolled in this study; 358 received SMT alone (SMT group), and the remaining 166 received PE-based NB-ALSS in addition to SMT (SMT+PE group). PSM generated 166 pairs of cases. In the SMT+PE group, 28-day, 90-day, and 1-year survival rates were 11.90, 8.00, and 10.90%, respectively, higher than those in the SMT group. Subgroup analysis revealed that PE-based NB-ALSS had the best efficacy in patients with ACLF grade 2 or MELD scores of 30-40 (MELD grade 3). In MELD grade 3 patients who received SMT+PE, 28-day, 90-day, and 1-year survival rates were improved by 18.60, 14.20, and 20.10%, respectively. According to multivariate Cox regression analysis, PE-based NB-ALSS was the only independent protective factor for HBV-ACLF patient prognosis at 28 days, 90 days, and 1 year (28 days, HR = 0.516, p = 0.001; 90 days, HR = 0.663, p = 0.010; 1 year, HR = 0.610, p = 0.051). For those who received SMT+PE therapy, PE-based NB-ALSS therapy frequency was the only independent protective factor for short-term prognosis (28-day, HR = 0.597, p = 0.001; 90-day, HR = 0.772, p = 0.018). Conclusions: This multicenter prospective study showed that the addition of PE-based NB-ALSS to SMT improves short-term (28/90 days and 1-year) outcomes in patients with HBV-ACLF, especially in MELD grade 3 patients. Optimization of PE-based NB-ALSS may improve prognosis or even save lives among HBV-ACLF patients.
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Affiliation(s)
- Yuan-yuan Chen
- Department of Infectious Diseases, Hubei Clinical Research Center for Precise Diagnosis and Therapy of Liver Cancer, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Hai Li
- Key Laboratory of Gastroenterology and Hepatology, Department of Gastroenterology, Renji Hospital, School of Medicine, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University, Chinese Ministry of Health (Shanghai Jiao Tong University), Shanghai, China
| | - Bao-yan Xu
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Xin Zheng
- Department of Infectious Diseases, Institute of Infection and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bei-ling Li
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xian-bo Wang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yan Huang
- Hunan Key Laboratory of Viral Hepatitis, Department of Infectious Disease, Xiangya Hospital, Central South University, Changsha, China
| | - Yan-hang Gao
- Department of Hepatology, The First Hospital of Jilin University, Changchun, China
| | - Zhi-ping Qian
- Department of Liver Intensive Care Unit, Shanghai Public Health Clinical Centre, Fudan University, Shanghai, China
| | - Feng Liu
- Department of Infectious Diseases and Hepatology, The Second Hospital of Shandong University, Jinan, China
| | - Xiao-bo Lu
- Liver Disease Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Jia Shang
- Department of Infectious Diseases, Henan Provincial People's Hospital, Zhengzhou, China
| | - Hai Li
- Infectious Disease Center, Affiliated Hospital of Logistics University of People's Armed Police Force, Tianjin, China
| | - Shao-yang Wang
- Department of Infectious Diseases, Fuzhou General Hospital of Nanjing Military Command, Fuzhou, China
| | - Yin-hua Zhang
- Department of Infectious Diseases, Hubei Clinical Research Center for Precise Diagnosis and Therapy of Liver Cancer, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Zhong-ji Meng
- Department of Infectious Diseases, Hubei Clinical Research Center for Precise Diagnosis and Therapy of Liver Cancer, Taihe Hospital, Hubei University of Medicine, Shiyan, China
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21
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Ferrer-Fàbrega J, Sampson-Dávila J, Forner A, Sapena V, Díaz A, Vilana R, Navasa M, Fondevila C, Miquel R, Ayuso C, García-Valdecasas JC, Bruix J, Reig M, Fuster J. Limited tumour progression beyond Milan criteria while on the waiting list does not result in unacceptable impairment of survival. J Hepatol 2021; 75:1154-1163. [PMID: 34171433 DOI: 10.1016/j.jhep.2021.06.015] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Revised: 05/24/2021] [Accepted: 06/05/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Defining optimum management of patients progressing beyond Milan criteria on the waiting list is a controversial topic. Our aim was to determine whether the policy of allowing a limited progression beyond enlistment criteria permits acceptable post-transplant outcomes in terms of survival and recurrence. METHODS Patients with hepatocellular carcinoma included on the waiting list for orthotopic liver transplantation (OLT) between January 1989 and December 2016 were analysed. Tumour features were assessed at inclusion on the waiting list, before OLT and at explant pathology. Patients were retained on the waiting list despite exceeding enlistment criteria if not presenting with macrovascular invasion, extrahepatic spread or cancer-related symptoms. RESULTS A total of 495 patients constituted the target population. Comparison between the Milan-in (n = 434) and Milan-out (n = 61) groups showed statistically significant differences in: largest tumour size; BCLC stage; patients treated before OLT; alpha-fetoprotein, and time on the waiting list. Milan-out patients showed a significantly higher number of poorly differentiated nodules, satellitosis and microscopic vascular invasion. The 1-, 3-, 5- and 10-year survival rate was 89.6%, 82.5%, 75%, and 55.5%, vs. 83.6%, 70.5%, 65.5%, and 53.9% for Milan-in/Milan-out patients, respectively. Recurrence rates at 1, 3, 5 and 10 years were 1.2%, 3.3%, 5.5%, and 10.8% vs. 7.1% 14.5%, 23%, and 23% for Milan-in and Milan-out patients, respectively (p <0.01). CONCLUSION This study shows that although limited tumour progression without reaching major adverse predictors (vascular invasion, extrahepatic spread, cancer symptoms) has an expected impact on recurrence rate, overall survival remains above the minimum proposed benchmark of 65% at 5 years. The clinically relevant increase in tumour recurrence must be considered when analysing the benefit of this approach in the face of limited organ supply. LAY SUMMARY When considering orthotopic liver transplantation for patients with hepatocellular carcinoma, optimum results are achieved when transplanting patients within the Milan criteria. However, the most appropriate strategy for patients who progress beyond these criteria while on the waiting list is still unclear. Herein, we show that transplantation is associated with acceptable overall survival in select patients who progress beyond the Milan criteria, although recurrence rates were notably higher. Therefore, the assessment of transplantation viability in these patients must consider the availability of organs and the impact on other patient categories.
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Affiliation(s)
- Joana Ferrer-Fàbrega
- Hepatobiliopancreatic Surgery and Liver and Pancreatic Transplantation Unit, Department of Surgery, Institute Clínic of Digestive and Metabolic Diseases (ICMDiM), Hospital Clínic, University of Barcelona, Barcelona, Spain; Barcelona Clínic Liver Cancer Group (BCLC), University of Barcelona, Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Barcelona, Spain.
| | - Jaime Sampson-Dávila
- Hepatobiliopancreatic Surgery and Liver and Pancreatic Transplantation Unit, Department of Surgery, Institute Clínic of Digestive and Metabolic Diseases (ICMDiM), Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Alejandro Forner
- Barcelona Clínic Liver Cancer Group (BCLC), University of Barcelona, Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Barcelona, Spain; Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain; Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Barcelona, Spain
| | - Victor Sapena
- Barcelona Clínic Liver Cancer Group (BCLC), University of Barcelona, Barcelona, Spain; Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Barcelona, Spain; Medical Statistics Core Facility, Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Alba Díaz
- Barcelona Clínic Liver Cancer Group (BCLC), University of Barcelona, Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Barcelona, Spain; Department of Pathology, Hospital Clínic. University of Barcelona, Barcelona, Spain
| | - Ramón Vilana
- Barcelona Clínic Liver Cancer Group (BCLC), University of Barcelona, Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Barcelona, Spain; Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Barcelona, Spain; Department of Radiology, Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Miquel Navasa
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Barcelona, Spain; Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain; Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Barcelona, Spain
| | - Constantino Fondevila
- Hepatobiliopancreatic Surgery and Liver and Pancreatic Transplantation Unit, Department of Surgery, Institute Clínic of Digestive and Metabolic Diseases (ICMDiM), Hospital Clínic, University of Barcelona, Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Barcelona, Spain; Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Barcelona, Spain
| | - Rosa Miquel
- Barcelona Clínic Liver Cancer Group (BCLC), University of Barcelona, Barcelona, Spain; Department of Pathology, Hospital Clínic. University of Barcelona, Barcelona, Spain; Liver Histopathology Laboratory, Institute of Liver Studies, King's College Hospital, London, UK
| | - Carmen Ayuso
- Barcelona Clínic Liver Cancer Group (BCLC), University of Barcelona, Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Barcelona, Spain; Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Barcelona, Spain; Department of Radiology, Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Juan Carlos García-Valdecasas
- Hepatobiliopancreatic Surgery and Liver and Pancreatic Transplantation Unit, Department of Surgery, Institute Clínic of Digestive and Metabolic Diseases (ICMDiM), Hospital Clínic, University of Barcelona, Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Barcelona, Spain; Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Barcelona, Spain
| | - Jordi Bruix
- Barcelona Clínic Liver Cancer Group (BCLC), University of Barcelona, Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Barcelona, Spain; Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain; Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Barcelona, Spain
| | - María Reig
- Barcelona Clínic Liver Cancer Group (BCLC), University of Barcelona, Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Barcelona, Spain; Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain; Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Barcelona, Spain
| | - Josep Fuster
- Hepatobiliopancreatic Surgery and Liver and Pancreatic Transplantation Unit, Department of Surgery, Institute Clínic of Digestive and Metabolic Diseases (ICMDiM), Hospital Clínic, University of Barcelona, Barcelona, Spain; Barcelona Clínic Liver Cancer Group (BCLC), University of Barcelona, Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Barcelona, Spain; Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Barcelona, Spain.
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D'Alessandro MCDO, Gomes AD, Morais JF, Mizubuti YGG, Silva TAD, Fernandes SM, Mendes LL, Correia MITD, Generoso SDV. SHORT-TERM EFFECT OF WHEY PROTEIN SUPPLEMENTATION ON THE QUALITY OF LIFE OF PATIENTS WAITING FOR LIVER TRANSPLANTATION: A DOUBLE BLINDED RANDOMIZED CLINICAL TRIAL. ABCD-ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA 2021; 34:e1596. [PMID: 34669886 PMCID: PMC8521869 DOI: 10.1590/0102-672020210002e1596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Accepted: 02/10/2021] [Indexed: 11/29/2022]
Abstract
Background:
Chronic liver disease is associated with malnutrition that negatively impacts a patient’s health-related quality of life (HRQoL).
Aim:
To evaluate the short-term effect of whey protein supplementation on the HRQoL and nutritional and functional status of patients waiting for liver transplantation.
Methods:
This was a double-blind randomized clinical trial with patients waiting for liver transplantation who were randomized into two groups: WP (whey protein supplementation) and the control (casein supplementation). Both groups received 40 g (20 g in the morning and 20 g in the evening) for 15 days. Nutritional and functional status were evaluated. Energy balance was calculated as the difference between energy intake (24-hour recall) and total energy expenditure (assessed by indirect calorimetry). The chronic liver disease questionnaire was used to assess HRQoL. All measurements were performed before and after the intervention.
Results:
Fifty-six patients were evaluated. Malnutrition was present in 56.9%, and it was directly associated with a poor HRQoL (p<0.05). No improvement on the nutritional and functional status was observed, in either group after protein supplementation. HRQoL improved after WP and casein supplementation, with no differences between groups (p>0.05). Patients who met protein requirements and had a positive energy balance demonstrated a higher HRQoL score (4.9, p<0.05), without between-group differences.
Conclusion:
Malnutrition substantially reduces HRQoL. Short-term WP or casein supplementation improved similarly the HRQoL.
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Affiliation(s)
| | - Amanda Dias Gomes
- Pharmacy School/Food of Science Program, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil
| | - Jéssica França Morais
- Nursing School, Department of Nutrition/Nutrition and Health Program, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil
| | | | - Thales Antônio da Silva
- Pharmacy School/Food of Science Program, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil
| | - Silvia Mauricio Fernandes
- Faculty of Medicine, Department of Surgery/Surgery and Ophthalmology Program, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil
| | - Larissa Loures Mendes
- Nursing School, Department of Nutrition/Nutrition and Health Program, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil
| | | | - Simone de Vasconcelos Generoso
- Nursing School, Department of Nutrition/Nutrition and Health Program, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil
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Potential Bias and Misconceptions in Liver Transplantation for Alcohol- and Obesity-Related Liver Disease. Am J Gastroenterol 2021; 116:2089-2097. [PMID: 34193797 DOI: 10.14309/ajg.0000000000001349] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 05/28/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Bias and misconceptions surrounding alcohol-related liver disease (ALD) and obesity-related liver disease (OLD) may lead to transplant listing inequities. The aim of this study was to evaluate patients, medical students, residents, fellows, and attending physicians for bias and misconceptions regarding liver transplantation (LT) for patients with ALD and OLD. METHODS Participants took a survey asking them whether patients with ALD who continue/discontinue drinking alcohol or patients with OLD who do/do not commit to a weight loss program deserve equal LT rights. A Likert scale was used for their responses. Participants also estimated 5-year survival and advanced fibrosis recurrence after LT. The primary outcome of the study was bias measured by expected agreement or disagreement to questions using a Likert scale, significant underestimation of a 5-year survival rate after LT, and significant overestimation of 5-year advanced fibrosis recurrence after LT. RESULTS A total of 381 participants were included in the analysis: 153 residents/fellows, 31 attending physicians, 98 medical students, and 99 patients. A higher percentage from all 4 participating groups either were neutral or disagreed with equal LT rights for patients with ALD who discontinue drinking compared with patients with OLD who commit to weight loss program. The attending physician group was the only group with a majority estimating >60% 5-year survival after LT in patients with ALD and OLD (P < 0.05). All 4 groups had a majority estimate >20% 5-year advanced fibrosis recurrence in patients with ALD and OLD (P > 0.05). DISCUSSION There seems to be current bias and misconceptions regarding LT for patients with ALD and OLD.
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Ember KJI, Hunt F, Jamieson LE, Hallett JM, Esser H, Kendall TJ, Clutton RE, Gregson R, Faulds K, Forbes SJ, Oniscu GC, Campbell CJ. Noninvasive Detection of Ischemic Vascular Damage in a Pig Model of Liver Donation After Circulatory Death. Hepatology 2021; 74:428-443. [PMID: 33420756 DOI: 10.1002/hep.31701] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 12/02/2020] [Accepted: 12/13/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS Liver graft quality is evaluated by visual inspection prior to transplantation, a process highly dependent on the surgeon's experience. We present an objective, noninvasive, quantitative way of assessing liver quality in real time using Raman spectroscopy, a laser-based tool for analyzing biomolecular composition. APPROACH AND RESULTS A porcine model of donation after circulatory death (DCD) with normothermic regional perfusion (NRP) allowed assessment of liver quality premortem, during warm ischemia (WI) and post-NRP. Ten percent of circulating blood volume was removed in half of experiments to simulate blood recovery for DCD heart removal. Left median lobe biopsies were obtained before circulatory arrest, after 45 minutes of WI, and after 2 hours of NRP and analyzed using spontaneous Raman spectroscopy, stimulated Raman spectroscopy (SRS), and staining. Measurements were also taken in situ from the porcine liver using a handheld Raman spectrometer at these time points from left median and right lateral lobes. Raman microspectroscopy detected congestion during WI by measurement of the intrinsic Raman signal of hemoglobin in red blood cells (RBCs), eliminating the need for exogenous labels. Critically, this microvascular damage was not observed during WI when 10% of circulating blood was removed before cardiac arrest. Two hours of NRP effectively cleared RBCs from congested livers. Intact RBCs were visualized rapidly at high resolution using SRS. Optical properties of ischemic livers were significantly different from preischemic and post-NRP livers as measured using a handheld Raman spectrometer. CONCLUSIONS Raman spectroscopy is an effective tool for detecting microvascular damage which could assist the decision to use marginal livers for transplantation. Reducing the volume of circulating blood before circulatory arrest in DCD may help reduce microvascular damage.
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Affiliation(s)
| | - Fiona Hunt
- Edinburgh Transplant Centre, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom
| | - Lauren E Jamieson
- Technology and Innovation Centre, University of Strathclyde, Glasgow, United Kingdom
| | - John M Hallett
- Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom
| | - Hannah Esser
- Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom
| | - Timothy J Kendall
- Edinburgh Pathology Department, The Royal Infirmary of Edinburgh, United Kingdom
- University of Edinburgh Centre for Inflammation Research, Edinburgh, United Kingdom
| | - R Eddie Clutton
- Roslin Institute, University of Edinburgh, Edinburgh, United Kingdom
| | - Rachael Gregson
- Roslin Institute, University of Edinburgh, Edinburgh, United Kingdom
| | - Karen Faulds
- Technology and Innovation Centre, University of Strathclyde, Glasgow, United Kingdom
| | - Stuart J Forbes
- Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom
| | - Gabriel C Oniscu
- Edinburgh Transplant Centre, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom
- Department of Clinical Sciences, University of Edinburgh, Edinburgh, United Kingdom
| | - Colin J Campbell
- Department of Chemistry, University of Edinburgh, Edinburgh, United Kingdom
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Passamonti SM, Cannavò A, Panigada M, Trunzo V, Bottazzi A, Longobardi A, Buonocore R, Fiorattini A, Torelli R, Piccolo G, De Feo TM. Donation after circulatory death and liver transplantation: a cohort study. Transpl Int 2021; 34:1271-1280. [PMID: 34002900 DOI: 10.1111/tri.13919] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Revised: 03/13/2021] [Accepted: 03/16/2021] [Indexed: 12/25/2022]
Abstract
Donations after circulatory death (DCD) are still challenging in Italy because of prolonged ischemia time (tWIT) due to the law and logistical issues. This cohort study was primarily aimed at assessing the association between successful transplantation and DCD types in the North Italy Transplant program. Adjusted risk ratios (RR) and 95% confidence intervals (CIs) for type III versus type II DCD were estimated using a Poisson regression model with a robust error variance. All consecutive DCD between 2008 and 2020 were included. Among 142 DCD, 102 were eligible for liver donation, and 96 were proposed: 68/69 (99%) and 28/33 (85%) type III and II DCD, respectively. Sixty-nine livers were recovered, 51/68 (75%) from type III and 18/28 (64%) from type II DCD, respectively (RR: 1.18; 95% CI: 0.87-1.60). After ex-vivo perfusion, 50/68 (74%) and 14/28 (50%) livers from type III and type II DCD were transplanted (RR: 1.49; 95% CI: 1.01-2.19). The estimate decreased after further controlling for tWIT (RR: 1.11; 95% CI: 0.55-2.24). Five patients (7.8%) experienced a PNF, 3/50 and 2/14 from type III and type II DCD, respectively. Type III DCD livers were more likely to be transplanted than type II. Warm ischemia time might explain this difference.
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Affiliation(s)
- Serena Maria Passamonti
- UOC Coordinamento Trapianti, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy
| | - Antonino Cannavò
- UOC Coordinamento Trapianti, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy
| | - Mauro Panigada
- Department of Anesthesia and Critical Care, Fondazione IRCCS Ca' Granda-Ospedale Maggiore, Milan, Italy
| | - Valentina Trunzo
- UOC Coordinamento Trapianti, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy
| | - Andrea Bottazzi
- Anestesia e Rianimazione 1, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy
| | - Antonio Longobardi
- UOC Coordinamento Trapianti, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy
| | - Ruggero Buonocore
- UOC Coordinamento Trapianti, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy
| | - Andrea Fiorattini
- UOC Coordinamento Trapianti, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy
| | - Rosanna Torelli
- UOC Coordinamento Trapianti, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy
| | | | - Tullia Maria De Feo
- UOC Coordinamento Trapianti, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy
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Finotti M, Romano M, Auricchio P, Scopelliti M, Brizzolari M, Grossi U, Piccino M, Benvenuti S, Morana G, Cillo U, Zanus G. Target Therapies for NASH/NAFLD: From the Molecular Aspect to the Pharmacological and Surgical Alternatives. J Pers Med 2021; 11:499. [PMID: 34199535 PMCID: PMC8229090 DOI: 10.3390/jpm11060499] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 05/25/2021] [Accepted: 05/28/2021] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease represents an increasing cause of chronic hepatic disease in recent years. This condition usually arises in patients with multiple comorbidities, the so-called metabolic syndrome. The therapeutic options are multiple, ranging from lifestyle modifications, pharmacological options, to liver transplantation in selected cases. The choice of the most beneficial one and their interactions can be challenging. It is mandatory to stratify the patients according to the severity of their disease to tailor the available treatments. In our contribution, we review the most recent pharmacological target therapies, the role of bariatric surgery, and the impact of liver transplantation on the NAFLD outcome.
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Affiliation(s)
- Michele Finotti
- 4th Surgery Unit, Regional Hospital Treviso, DISCOG, University of Padua, 31100 Padua, Italy; (M.R.); (M.S.); (M.B.); (U.G.); (M.P.); (G.Z.)
| | - Maurizio Romano
- 4th Surgery Unit, Regional Hospital Treviso, DISCOG, University of Padua, 31100 Padua, Italy; (M.R.); (M.S.); (M.B.); (U.G.); (M.P.); (G.Z.)
| | - Pasquale Auricchio
- Hepatobiliary Surgery and Liver Transplantation Unit, DISCOG, University of Padua, 35121 Padua, Italy; (P.A.); (U.C.)
| | - Michele Scopelliti
- 4th Surgery Unit, Regional Hospital Treviso, DISCOG, University of Padua, 31100 Padua, Italy; (M.R.); (M.S.); (M.B.); (U.G.); (M.P.); (G.Z.)
| | - Marco Brizzolari
- 4th Surgery Unit, Regional Hospital Treviso, DISCOG, University of Padua, 31100 Padua, Italy; (M.R.); (M.S.); (M.B.); (U.G.); (M.P.); (G.Z.)
| | - Ugo Grossi
- 4th Surgery Unit, Regional Hospital Treviso, DISCOG, University of Padua, 31100 Padua, Italy; (M.R.); (M.S.); (M.B.); (U.G.); (M.P.); (G.Z.)
| | - Marco Piccino
- 4th Surgery Unit, Regional Hospital Treviso, DISCOG, University of Padua, 31100 Padua, Italy; (M.R.); (M.S.); (M.B.); (U.G.); (M.P.); (G.Z.)
| | - Stefano Benvenuti
- Gastroenterology Unit (IV), Cà Foncello Regional Hospital, 31100 Treviso, Italy;
| | - Giovanni Morana
- Division of Radiology, Treviso Regional Hospital, 31100 Treviso, Italy;
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplantation Unit, DISCOG, University of Padua, 35121 Padua, Italy; (P.A.); (U.C.)
| | - Giacomo Zanus
- 4th Surgery Unit, Regional Hospital Treviso, DISCOG, University of Padua, 31100 Padua, Italy; (M.R.); (M.S.); (M.B.); (U.G.); (M.P.); (G.Z.)
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Xu G, Jin B, Xian X, Yang H, Zhao H, Du S, Makuuchi M, Pawlik TM, Mao Y. Evolutions in the Management of Hepatocellular Carcinoma over Last 4 Decades: An Analysis from the 100 Most Influential Articles in the Field. Liver Cancer 2021; 10:137-150. [PMID: 33977090 PMCID: PMC8077437 DOI: 10.1159/000513412] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Accepted: 11/26/2020] [Indexed: 02/04/2023] Open
Abstract
INTRODUCTION Over the past 4 decades, the management of hepatocellular carcinoma (HCC) has changed dramatically. The publications that have had the most significant impact on HCC management have not been quantitatively analyzed. In this article, we analyzed the 100 most influential articles over the past 4 decades using bibliometric citation analysis to characterize the evolution in HCC treatment. METHODS The top-cited publications were identified and analyzed from the Clarivate Analytics Web of Science Core Collection database. RESULTS The 100 most cited articles were identified with an average of 738 citations (range: 349-6,799). There was an increase in the number of influential articles in the late 1990s, which was paralleled by an increase in reports focused on locoregional treatment of HCC. Most top 100 articles came from the USA (n = 35), followed by Italy (n = 28), mainland China (n = 26), and Japan (n = 24). The surgical management was the most studied topic (n = 33). The Annals of Surgery published the highest number of papers (n = 26) with 13,978 citations. While other 3 topics (surgical management, locoregional treatment, and outcome prediction) declined among publications beginning in the 2000s, there was an emergence of highly cited papers on targeted drugs and immune checkpoint inhibitors with a concomitant increase in the number of publications on systemic therapy. CONCLUSIONS Based on bibliometric analysis of the literature over the last 40 years, a comprehensive analysis of the most historically significant HCC management articles highlighted the key contributions made to the evolution and advancement of this specialist field. The data should provide clinicians and researchers insight into future directions relative to the advancement of HCC management.
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Affiliation(s)
- Gang Xu
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC and Chinese Academy of Medical Sciences, Beijing, China
| | - Bao Jin
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC and Chinese Academy of Medical Sciences, Beijing, China
| | - Xiaomeng Xian
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC and Chinese Academy of Medical Sciences, Beijing, China
| | - Huayu Yang
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC and Chinese Academy of Medical Sciences, Beijing, China
| | - Haitao Zhao
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC and Chinese Academy of Medical Sciences, Beijing, China
| | - Shunda Du
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC and Chinese Academy of Medical Sciences, Beijing, China
| | - Masatoshi Makuuchi
- President of the Koto Hospital, Tokyo, Japan,***Prof. Masatoshi Makuuchi, MD, President of the Koto Hospital, Tokyo (Japan),
| | - Timothy M. Pawlik
- Department of Surgery, Wexner Medical Center, The Ohio State University, Columbus, Ohio, USA,**Timothy Pawlik, Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH (USA),
| | - Yilei Mao
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC and Chinese Academy of Medical Sciences, Beijing, China,*Yilei Mao, Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC and Chinese Academy of Medical Sciences, Beijing 100730 (China),
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Clinical Application of Human Induced Pluripotent Stem Cell-Derived Organoids as an Alternative to Organ Transplantation. Stem Cells Int 2021; 2021:6632160. [PMID: 33679987 PMCID: PMC7929656 DOI: 10.1155/2021/6632160] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 01/19/2021] [Accepted: 02/17/2021] [Indexed: 12/11/2022] Open
Abstract
Transplantation is essential and crucial for individuals suffering from end-stage organ failure diseases. However, there are still many challenges regarding these procedures, such as high rates of organ rejection, shortage of organ donors, and long waiting lines. Thus, investments and efforts to develop laboratory-grown organs have increased over the past years, and with the recent progress in regenerative medicine, growing organs in vitro might be a reality within the next decades. One of the many different strategies to address this issue relies on organoid technology, a miniaturized and simplified version of an organ. Here, we address recent progress on organoid research, focusing on transplantation of intestine, retina, kidney, liver, pancreas, brain, lung, and heart organoids. Also, we discuss the main outcomes after organoid transplantation, common challenges faced by these promising regenerative medicine approaches, and future perspectives on the field.
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Alcohol Recidivism Following Transjugular Intrahepatic Portosystemic Shunt Placement: Frequency and Predictive Factors. Cardiovasc Intervent Radiol 2021; 44:758-765. [PMID: 33415418 DOI: 10.1007/s00270-020-02754-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Accepted: 12/22/2020] [Indexed: 12/17/2022]
Abstract
PURPOSE To determine the frequency and predictive factors for alcohol recidivism following transjugular intrahepatic portosystemic shunts (TIPS) placed in patients with alcoholic cirrhosis. METHODS One hundred ninety-nine patients who had a TIPS placed at a single institution for different indications in the setting of alcoholic cirrhosis were reviewed. Length of sobriety prior to TIPS placement and maintained sobriety at 1, 3 and 6-12 months after TIPS placement were recorded. Smoking history, substance abuse and psychiatric comorbidities were also recorded as was ascitic response to TIPS at 1, 3 and 6-12 months. RESULTS At 1 month 11/199 (5.5%) patients had experienced a relapse while, 20/199 (10.1%) had at 3 months, and 44/199 (22.1%) had at 12 months. There was no difference in ascitic response in those who did and did not relapse at 1 month (p = 0.57), 3 months (p = 1.00) or 1 year (p = 0.44). The mean time of sobriety at the time of TIPS placement for those who relapsed by 12 months was significantly less than those who did not relapse (5.11 (1.10-7.90) months vs 18.32 (8.63-48.12) months, p < 0.001). Concurrent psychiatric comorbidity (p < 0.001), substance abuse (p < 0.001), age less than 40 (p = 0.004) and smoking history at the time of procedure (p < 0.001) were also associated with alcohol relapse. CONCLUSION Recidivism is a frequent issue for patients following TIPS placement; those who have concurrent psychiatric comorbidity, substance abuse, smoking history are younger than 40 and shorter sobriety duration prior to TIPS may be at increased risk.
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Ko YC, Tsai HI, Lee CW, Lin JR, Lee WC, Yu HP. A nomogram for prediction of early allograft dysfunction in living donor liver transplantation. Medicine (Baltimore) 2020; 99:e22749. [PMID: 33080739 PMCID: PMC7571974 DOI: 10.1097/md.0000000000022749] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Liver transplantation is the treatment of choice for end-stage liver diseases. However, early allograft dysfunction (EAD) is frequently encountered and associated with graft loss or mortality after transplantation. This study aimed to establish a predictive model of EAD after living donor liver transplantation. A total of 77 liver transplants were recruited to the study. Multivariate analysis was utilized to identify significant risk factors for EAD. A nomogram was constructed according to the contributions of the risk factors. The predictive values were determined by discrimination and calibration methods. A cohort of 30 patients was recruited to validate this predictive model. Four independent risk factors, including donor age, intraoperative blood loss, preoperative alanine aminotransferase (ALT), and reperfusion total bilirubin, were identified and used to build the nomogram. The c-statistics of the primary cohort and the validation group were 0.846 and 0.767, respectively. The calibration curves for the probability of EAD presented an acceptable agreement between the prediction by the nomogram and the actual incidence. In conclusion, the study developed a new nomogram for predicting the risk of EAD following living donor liver transplantation. This model may help clinicians to determine individual risk of EAD following living donor liver transplantation.
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Affiliation(s)
- Yu-Chen Ko
- Department of Anesthesiology, Chang Gung Memorial Hospital
| | - Hsin-I Tsai
- Department of Anesthesiology, Chang Gung Memorial Hospital
- College of Medicine, Chang Gung University
| | - Chao-Wei Lee
- College of Medicine, Chang Gung University
- Department of General Surgery, Chang Gung Memorial Hospital
| | - Jr-Rung Lin
- Clinical Informatics and Medical Statistics Research Center and Graduate Institute of Clinical Medicine, Chang Gung University
| | - Wei-Chen Lee
- College of Medicine, Chang Gung University
- Department of General Surgery, Chang Gung Memorial Hospital
- Department of Liver and Transplantation Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Huang-Ping Yu
- Department of Anesthesiology, Chang Gung Memorial Hospital
- College of Medicine, Chang Gung University
- Department of Anesthesiology, Xiamen Chang Gung Hospital, Xiamen, China
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Early identification using the referral system prolonged the time to onset for hepatic encephalopathy after diagnosing severe acute liver injury. Sci Rep 2020; 10:17280. [PMID: 33057105 PMCID: PMC7560720 DOI: 10.1038/s41598-020-74466-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Accepted: 10/01/2020] [Indexed: 12/26/2022] Open
Abstract
In 2004, we implemented a referral system for patients with acute liver injury (ALI) based on an established formula that estimates the risk of progression to acute live failure (ALF); however, the benefits of the system for patients with severe acute liver injury (SLI) remain unclear. We have evaluated the clinical significance of the referral system for SLI patients. Patients with ALI/SLI who were consecutively and prospectively listed on the system between 2004 and 2018 were analyzed. Of the 371 ALI/SLI/ALF patients on the system, 124 satisfied the criteria for SLI; 34 of these 124 progressed to SLI after registration. Multivariate analysis using age, sex, AST, ALT, creatinine, total bilirubin, prothrombin, presence of hepatic encephalopathy (HE), and SLI at registration revealed that HE was associated with high mortality. Among the 23 patients who developed HE, five who progressed to SLI after registration showed an increased time to HE development compared with patients who had SLI at the time of registration. However, there was no significant difference in survival time after HE development. We concluded that early identification of SLI patients using the referral system increased the time from SLI diagnosis to HE development.
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Leung KK, Deeb M, Hirschfield GM. Review article: pathophysiology and management of primary biliary cholangitis. Aliment Pharmacol Ther 2020; 52:1150-1164. [PMID: 32813299 DOI: 10.1111/apt.16023] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 05/13/2020] [Accepted: 07/18/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND Primary biliary cholangitis (PBC), an immune-mediated disease characterised by destruction of intrahepatic bile ducts, results in progressive damage to the biliary tree, cholestasis and ultimately advanced liver disease. In the last decade, advances in practice have improved clinical care, driven novel therapeutic options and improved risk stratification tools. AIMS To provide an overview of the disease characteristics of PBC and review a patient-centred management approach for the clinical team caring for those with PBC. METHODS We reviewed the current literature and guidelines on PBC with a focus on management and therapies. RESULTS A confident diagnosis of PBC is usually made based on serum liver tests and immune serology. Management of PBC should focus on three main 'process' pillars: (a) treat and risk-stratify through use of biochemical and prognostic criteria; (b) manage concurrent symptoms and other associated diseases; and (c) stage disease, monitor progression and prevent complications. With ongoing complexities in management, including a newly licensed therapy (obeticholic acid) and alternative non-licensed treatments and ongoing clinical trials, discussion with PBC expert centres is encouraged. CONCLUSIONS PBC is a dynamic disease wherein current treatment goals have become appropriately ambitious. Goals of care should prioritise prevention of end-stage liver disease and amelioration of patient symptom burden for all.
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Affiliation(s)
- Kristel K Leung
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, ON, Canada.,Toronto Centre for Liver Disease, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Maya Deeb
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, ON, Canada.,Toronto Centre for Liver Disease, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Gideon M Hirschfield
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, ON, Canada.,Toronto Centre for Liver Disease, University Health Network, University of Toronto, Toronto, Ontario, Canada
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van der Mark SC, Hoek RAS, Hellemons ME. Developments in lung transplantation over the past decade. Eur Respir Rev 2020; 29:190132. [PMID: 32699023 PMCID: PMC9489139 DOI: 10.1183/16000617.0132-2019] [Citation(s) in RCA: 81] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2019] [Accepted: 01/30/2020] [Indexed: 12/12/2022] Open
Abstract
With an improved median survival of 6.2 years, lung transplantation has become an increasingly acceptable treatment option for end-stage lung disease. Besides survival benefit, improvement of quality of life is achieved in the vast majority of patients. Many developments have taken place in the field of lung transplantation over the past decade. Broadened indication criteria and bridging techniques for patients awaiting lung transplantation have led to increased waiting lists and changes in allocation schemes worldwide. Moreover, the use of previously unacceptable donor lungs for lung transplantation has increased, with donations from donors after cardiac death, donors with increasing age and donors with positive smoking status extending the donor pool substantially. Use of ex vivo lung perfusion further increased the number of lungs suitable for lung transplantation. Nonetheless, the use of these previously unacceptable lungs did not have detrimental effects on survival and long-term graft outcomes, and has decreased waiting list mortality. To further improve long-term outcomes, strategies have been proposed to modify chronic lung allograft dysfunction progression and minimise toxic immunosuppressive effects. This review summarises the developments in clinical lung transplantation over the past decade.
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Affiliation(s)
- Sophie C van der Mark
- Dept of Pulmonary Medicine, Division of Interstitial Lung Disease, Erasmus Medical Centre Rotterdam, Rotterdam, The Netherlands
- Authors contributed equally
| | - Rogier A S Hoek
- Dept of Pulmonary Medicine, Division of Lung Transplantation, Erasmus Medical Centre Rotterdam, Rotterdam, The Netherlands
- Authors contributed equally
| | - Merel E Hellemons
- Dept of Pulmonary Medicine, Division of Interstitial Lung Disease, Erasmus Medical Centre Rotterdam, Rotterdam, The Netherlands
- Dept of Pulmonary Medicine, Division of Lung Transplantation, Erasmus Medical Centre Rotterdam, Rotterdam, The Netherlands
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An T, Dean M, Flower R, Tatzenko T, Chan HT, Kiely P, Faddy HM. Understanding occult hepatitis C infection. Transfusion 2020; 60:2144-2152. [PMID: 33460181 DOI: 10.1111/trf.16006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Revised: 06/16/2020] [Accepted: 06/18/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Occult hepatitis C infection (OCI) is a type of hepatitis C virus (HCV) infection, defined as the presence of HCV RNA in hepatocytes or peripheral blood mononuclear cells (PBMCs) and the absence of HCV RNA in serum. STUDY DESIGN AND METHODS A literature review was conducted to identify articles that characterized OCI as a disease, including its epidemiology, mode of transmission, pattern of infection, progression, and treatment. RESULTS OCI patients experience a milder degree of inflammatory and cirrhotic changes than patients with chronic hepatitis C. OCI is transmissible parenterally both in vivo and in vitro, however the duration and outcome of OCI remains unclear. OCI is most consistently found in patients with previous hepatitis C disease and hemodialysis patients. Beyond the at-risk populations, OCI has also been demonstrated among healthy individuals and blood donors. CONCLUSIONS This review summarises our current understanding of OCI and suggests areas for further research to improve our understanding of this phenomenon, including a better understanding of its epidemiology and full clinical course. The current understanding of OCI and its clinical implications remain limited. Further standardized detection methods, ongoing surveillance, and investigation of its potential transmissions are required.
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Affiliation(s)
- Timothy An
- Research and Development, Australia Red Cross Lifeblood, Kelvin Grove, Queensland, Australia.,Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
| | - Melinda Dean
- Research and Development, Australia Red Cross Lifeblood, Kelvin Grove, Queensland, Australia.,School of Health and Sports Science, University of the Sunshine Coast, Brisbane, Queensland, Australia
| | - Robert Flower
- Research and Development, Australia Red Cross Lifeblood, Kelvin Grove, Queensland, Australia
| | - Tayla Tatzenko
- Research and Development, Australia Red Cross Lifeblood, Kelvin Grove, Queensland, Australia.,Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
| | - Hiu Tat Chan
- Australia Red Cross Lifeblood, Melbourne, Victoria, Australia
| | - Philip Kiely
- Australia Red Cross Lifeblood, Melbourne, Victoria, Australia
| | - Helen M Faddy
- Research and Development, Australia Red Cross Lifeblood, Kelvin Grove, Queensland, Australia.,Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.,School of Health and Sports Science, University of the Sunshine Coast, Brisbane, Queensland, Australia
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Wingfield LR, Ceresa C, Thorogood S, Fleuriot J, Knight S. Using Artificial Intelligence for Predicting Survival of Individual Grafts in Liver Transplantation: A Systematic Review. Liver Transpl 2020; 26:922-934. [PMID: 32274856 DOI: 10.1002/lt.25772] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Revised: 03/06/2020] [Accepted: 03/13/2020] [Indexed: 12/12/2022]
Abstract
The demand for liver transplantation far outstrips the supply of deceased donor organs, and so, listing and allocation decisions aim to maximize utility. Most existing methods for predicting transplant outcomes use basic methods, such as regression modeling, but newer artificial intelligence (AI) techniques have the potential to improve predictive accuracy. The aim was to perform a systematic review of studies predicting graft outcomes following deceased donor liver transplantation using AI techniques and to compare these findings to linear regression and standard predictive modeling: donor risk index (DRI), Model for End-Stage Liver Disease (MELD), and Survival Outcome Following Liver Transplantation (SOFT). After reviewing available article databases, a total of 52 articles were reviewed for inclusion. Of these articles, 9 met the inclusion criteria, which reported outcomes from 18,771 liver transplants. Artificial neural networks (ANNs) were the most commonly used methodology, being reported in 7 studies. Only 2 studies directly compared machine learning (ML) techniques to liver scoring modalities (i.e., DRI, SOFT, and balance of risk [BAR]). Both studies showed better prediction of individual organ survival with the optimal ANN model, reporting an area under the receiver operating characteristic curve (AUROC) 0.82 compared with BAR (0.62) and SOFT (0.57), and the other ANN model gave an AUC ROC of 0.84 compared with a DRI (0.68) and SOFT (0.64). AI techniques can provide high accuracy in predicting graft survival based on donors and recipient variables. When compared with the standard techniques, AI methods are dynamic and are able to be trained and validated within every population. However, the high accuracy of AI may come at a cost of losing explainability (to patients and clinicians) on how the technology works.
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Affiliation(s)
- Laura R Wingfield
- Nuffield Department of Surgical Sciences, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
| | - Carlo Ceresa
- Nuffield Department of Surgical Sciences, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
| | - Simon Thorogood
- The School of Informatics, Informatics Forum, University of Edinburgh, Edinburgh, United Kingdom
| | - Jacques Fleuriot
- The School of Informatics, Informatics Forum, University of Edinburgh, Edinburgh, United Kingdom
| | - Simon Knight
- Nuffield Department of Surgical Sciences, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
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Joffe AR, Wong K, Bond GY, Khodayari Moez E, Acton BV, Dinu IA, Yap JYK, Robertson CMT. Kindergarten-age neurocognitive, functional, and quality-of-life outcomes after liver transplantation at under 6 years of age. Pediatr Transplant 2020; 24:e13624. [PMID: 31833183 DOI: 10.1111/petr.13624] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Revised: 10/22/2019] [Accepted: 11/15/2019] [Indexed: 12/23/2022]
Abstract
BACKGROUND We aimed to describe school-entry age neurocognitive, functional, and HRQL outcomes and their predictors after liver transplant done at age <6 years. METHODS A prospective cohort of all (n = 69) children surviving liver transplant from 1999 to 2014 were assessed at age 55.4 (SD 7.2) months and 38.6 (12.4) months after transplant. Assessment included: the Wechsler Preschool and Primary Scales of Intelligence, Beery-Buktenica Developmental Test of VMI, Adaptive Behavior Assessment System caregiver-completed questionnaire, and PedsQL 4.0 Generic Core Scales. Univariate and multiple linear regression determined predictors of outcomes at P < .05. RESULTS Neurocognitive and functional outcomes were on average within 1 SD of population norms, although shifted to the left (P ≤ .03), with more patients than expected having scores >2 (3.7-5.9 times more, P ≤ .007) SD below population norms. Total and Summary HRQL scores were statistically significantly lower than the healthy normative population (P ≤ .02) and a congenital heart disease group (P ≤ .02), but similar to children with other chronic health conditions; differences often exceeded the MCID and were lowest in the School functioning domain. There were few predictors on multiple linear regressions, and we could not confirm previous studies that suggested various inconsistent predictors of outcomes. Neurocognitive and functional outcomes scores were highly correlated with HRQL scores except for the School functioning domain, but did not fully explain them. CONCLUSIONS Long-term follow-up of this vulnerable population is important in order to facilitate support for the patient and family, and early intervention for any difficulties identified.
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Affiliation(s)
- Ari R Joffe
- Department of Pediatrics, Stollery Children's Hospital, University of Alberta, Edmonton, AB, Canada
| | - Kerry Wong
- Department of Pediatrics, Stollery Children's Hospital, University of Alberta, Edmonton, AB, Canada
| | - Gwen Y Bond
- Glenrose Rehabilitation Hospital, Edmonton, AB, Canada
| | | | - Bryan V Acton
- Department of Psychology, University of Saskatoon, Saskatoon, SK, Canada
| | - Irina A Dinu
- School of Public Health, University of Alberta, Edmonton, AB, Canada
| | - Jason Y K Yap
- Pediatric Gastroenterology, The Royal Children's Hospital, Melbourne, VIC, Australia
| | - Charlene M T Robertson
- Department of Pediatrics, Stollery Children's Hospital, University of Alberta, Edmonton, AB, Canada.,Glenrose Rehabilitation Hospital, Edmonton, AB, Canada
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Suri JS, Danford CJ, Patwardhan V, Bonder A. Mortality on the UNOS Waitlist for Patients with Autoimmune Liver Disease. J Clin Med 2020; 9:E319. [PMID: 31979326 PMCID: PMC7074547 DOI: 10.3390/jcm9020319] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2019] [Revised: 01/14/2020] [Accepted: 01/20/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Outcomes on the liver transplant waitlist can vary by etiology. Our aim is to investigate differences in waitlist mortality of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) using the United Network for Organ Sharing (UNOS) database. METHODS We identified patients who were listed for liver transplantation from 1987 to 2016 with a primary diagnosis of AIH, PBC, or PSC. We excluded patients with overlap syndromes, acute hepatic necrosis, missing data, and those who were children. The primary outcome was death or removal from the waitlist due to clinical deterioration. We compared waitlist survival using competing risk analysis. RESULTS Between 1987 and 2016, there were 7412 patients listed for liver transplant due to AIH, 8119 for PBC, and 10,901 for PSC. Patients with AIH were younger, more likely to be diabetic, and had higher listing model for end-stage liver disease (MELD) scores compared to PBC and PSC patients. Patients with PBC and AIH were more likely to be removed from the waitlist due to death or clinical deterioration. On competing risk analysis, AIH patients had a similar risk of being removed from the waitlist compared to those with PBC (subdistribution hazard ratio (SHR) 0.94, 95% CI 0.85-1.03) and higher risk of removal compared to those with PSC (SHR 0.8, 95% CI 0.72 to 0.89). CONCLUSION Autoimmune hepatitis carries a similar risk of waitlist removal to PBC and a higher risk than PSC. The etiology of this disparity is not entirely clear and deserves further investigation.
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Affiliation(s)
| | | | | | - Alan Bonder
- Liver Center, Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
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38
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Liver Transplantation. THE CRITICALLY ILL CIRRHOTIC PATIENT 2020. [PMCID: PMC7122092 DOI: 10.1007/978-3-030-24490-3_14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The field of liver transplantation has changed since the MELD scoring system became the most widely used donor allocation tool. Due to the MELD-based allocation system, sicker patients with higher MELD scores are being transplanted. Persistent organ donor shortages remain a challenging issue, and as a result, the wait-list mortality is a persistent problem for most of the regions. This chapter focuses on deceased donor and live donor liver transplantation in patients with complications of portal hypertension. Special attention will also be placed on donor-recipient matching, perioperative management of transplant patients, and the impact of hepatic hemodynamics on transplantation.
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39
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Crismale JF, Ahmad J. Expanding the donor pool: Hepatitis C, hepatitis B and human immunodeficiency virus-positive donors in liver transplantation. World J Gastroenterol 2019; 25:6799-6812. [PMID: 31885421 PMCID: PMC6931007 DOI: 10.3748/wjg.v25.i47.6799] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Revised: 11/26/2019] [Accepted: 11/29/2019] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation (LT) remains the best option for patients with end-stage liver disease but the demand for organs from deceased donors continues to outweigh the available supply. The advent of highly effective anti-viral treatments has reduced the number of patients undergoing LT for hepatitis C (HCV) and hepatitis B (HBV) related liver disease and yet the number of patients waiting for LT continues to increase, driven by an increase in the patients listed with a diagnosis of cirrhosis due to non-alcoholic steatohepatitis and alcohol-related liver disease. In addition, human immunodeficiency virus (HIV) infection, which was previously a contra-indication for LT, is no longer a fatal disease due to the effectiveness of HIV therapy and patients with HIV and liver disease are now developing indications for LT. The rising demand for LT is projected to increase further in the future, thus driving the need to investigate potential means of expanding the pool of potential donors. One mechanism for doing so is utilizing organs from donors that previously would have been discarded or used only in exceptional circumstances such as HCV-positive, HBV-positive, and HIV-positive donors. The advent of highly effective anti-viral therapy has meant that these organs can now be used with excellent outcomes in HCV, HBV or HIV infected recipients and in some cases uninfected recipients.
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Affiliation(s)
- James F Crismale
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
| | - Jawad Ahmad
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
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40
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Natural Flavonol, Myricetin, Enhances the Function and Survival of Cryopreserved Hepatocytes In Vitro and In Vivo. Int J Mol Sci 2019; 20:ijms20246123. [PMID: 31817281 PMCID: PMC6940939 DOI: 10.3390/ijms20246123] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Revised: 11/28/2019] [Accepted: 12/02/2019] [Indexed: 12/15/2022] Open
Abstract
To improve the therapeutic potential of hepatocyte transplantation, the effects of the mitogen-activated protein kinase kinase 4 (MKK4) inhibitor, myricetin (3,3′,4′,5,5′,7-hexahydroxylflavone) were examined using porcine and human hepatocytes in vitro and in vivo. Hepatocytes were cultured, showing the typical morphology of hepatic parenchymal cell under 1–10 µmol/L of myricetin, keeping hepatocyte specific gene expression, and ammonia removal activity. After injecting the hepatocytes into neonatal Severe combined immunodeficiency (SCID) mouse livers, cell colony formation was found at 10–15 weeks after transplantation. The human albumin levels in the sera of engrafted mice were significantly higher in the recipients of myricetin-treated cells than non-treated cells, corresponding to the size of the colonies. In terms of therapeutic efficacy, the injection of myricetin-treated hepatocytes significantly prolonged the survival of ornithine transcarbamylase-deficient SCID mice from 32 days (non-transplant control) to 54 days. Biochemically, the phosphorylation of MKK4 was inhibited in the myricetin-treated hepatocytes. These findings suggest that myricetin has a potentially therapeutic benefit that regulates hepatocyte function and survival, thereby treating liver failure.
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41
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Dolgin NH, Movahedi B, Anderson FA, Brüggenwirth IMA, Martins PN, Bozorgzadeh A. Impact of recipient functional status on 1-year liver transplant outcomes. World J Transplant 2019; 9:145-157. [PMID: 31850158 PMCID: PMC6914386 DOI: 10.5500/wjt.v9.i7.145] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Revised: 10/16/2019] [Accepted: 11/07/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND The Karnofsky Performance Status (KPS) scale has been widely validated for clinical practice for over 60 years.
AIM To examine the extent to which poor pre-transplant functional status, assessed using the KPS scale, is associated with increased risk of mortality and/or graft failure at 1-year post-transplantation.
METHODS This study included 38278 United States adults who underwent first, non-urgent, liver-only transplantation from 2005 to 2014 (Scientific Registry of Transplant Recipients). Functional impairment/disability was categorized as severe, moderate, or none/normal. Analyses were conducted using multivariable-adjusted Cox survival regression models.
RESULTS The median age was 56 years, 31% were women, median pre-transplant Model for End-Stage for Liver Disease score was 18. Functional impairment was present in 70%; one-quarter of the sample was severely disabled. After controlling for key recipient and donor factors, moderately and severely disabled patients had a 1-year mortality rate of 1.32 [confidence interval (CI): 1.21-1.44] and 1.73 (95%CI: 1.56-1.91) compared to patients with no impairment, respectively. Subjects with moderate and severe disability also had a multivariable-adjusted 1-year graft failure rate of 1.13 (CI: 1.02-1.24) and 1.16 (CI: 1.02-1.31), respectively.
CONCLUSION Pre-transplant functional status is a useful prognostic indicator for 1-year post-transplant patient and graft survival.
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Affiliation(s)
- Natasha H Dolgin
- Department of Surgery, Division of Organ Transplantation, UMass Memorial Medical Center, University of Massachusetts Medical School, Worcester, MA 01605, United States
- Department of Quantitative Health Sciences, Clinical and Population Health Research Program, University of Massachusetts Medical School, Worcester, MA 01605, United States
- Department of Surgery, Center for Outcomes Research, University of Massachusetts Medical School, Worcester, MA 01655, United States
| | - Babak Movahedi
- Department of Surgery, Division of Organ Transplantation, UMass Memorial Medical Center, University of Massachusetts Medical School, Worcester, MA 01605, United States
| | - Frederick A Anderson
- Department of Surgery, Center for Outcomes Research, University of Massachusetts Medical School, Worcester, MA 01655, United States
| | - Isabel MA Brüggenwirth
- Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, Groningen 9713GZ, Netherlands
| | - Paulo N Martins
- Department of Surgery, Division of Organ Transplantation, UMass Memorial Medical Center, University of Massachusetts Medical School, Worcester, MA 01605, United States
| | - Adel Bozorgzadeh
- Department of Surgery, Division of Organ Transplantation, UMass Memorial Medical Center, University of Massachusetts Medical School, Worcester, MA 01605, United States
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Roussel A, Sage E, Massard G, Thomas PA, Castier Y, Fadel E, Le Pimpec-Barthes F, Maury JM, Jougon J, Lacoste P, Claustre J, Dahan M, Pirvu A, Tissot A, Thumerel M, Drevet G, Pricopi C, Le Pavec J, Mal H, D'Journo XB, Kessler R, Roux A, Dorent R, Thabut G, Mordant P. Impact of donor, recipient and matching on survival after high emergency lung transplantation in France. Eur Respir J 2019; 54:13993003.00096-2019. [PMID: 31601709 DOI: 10.1183/13993003.00096-2019] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2019] [Accepted: 07/27/2019] [Indexed: 11/05/2022]
Abstract
INTRODUCTION Since July 2007, the French high emergency lung transplantation (HELT) allocation procedure prioritises available lung grafts to waiting patients with imminent risk of death. The relative impacts of donor, recipient and matching on the outcome following HELT remain unknown. We aimed at deciphering the relative impacts of donor, recipient and matching on the outcome following HELT in an exhaustive administrative database. METHODS All lung transplantations performed in France were prospectively registered in an administrative database. We retrospectively reviewed the procedures performed between July 2007 and December 2015, and analysed the impact of donor, recipient and matching on overall survival after the HELT procedure by fitting marginal Cox models. RESULTS During the study period, 2335 patients underwent lung transplantation in 11 French centres. After exclusion of patients with chronic obstructive pulmonary disease/emphysema, 1544 patients were included: 503 HELT and 1041 standard lung transplantation allocations. HELT was associated with a hazard ratio for death of 1.41 (95% CI 1.22-1.64; p<0.0001) in univariate analysis, decreasing to 1.32 (95% CI 1.10-1.60) after inclusion of recipient characteristics in a multivariate model. A donor score computed to predict long-term survival was significantly different between the HELT and standard lung transplantation groups (p=0.014). However, the addition of donor characteristics to recipient characteristics in the multivariate model did not change the hazard ratio associated with HELT. CONCLUSIONS This exhaustive French national study suggests that HELT is associated with an adverse outcome compared with regular allocation. This adverse outcome is mainly related to the severity status of the recipients rather than donor or matching characteristics.
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Affiliation(s)
- Arnaud Roussel
- Hôpital Bichat, Université Paris-Diderot, INSERM 1152, Paris, France .,Agence de la Biomédecine, Saint Denis, France
| | - Edouard Sage
- Hôpital Foch, Université Versailles-Saint-Quentin, Suresnes, France
| | | | | | - Yves Castier
- Hôpital Bichat, Université Paris-Diderot, INSERM 1152, Paris, France
| | - Elie Fadel
- Hôpital Marie-Lannelongue, Université Paris-Sud, Le Plessis Robinson, France
| | | | | | - Jacques Jougon
- Hôpital du Haut Lévèque, CHU de Bordeaux, Pessac, France
| | | | | | - Marcel Dahan
- Hôpital Larrey, CHU de Toulouse, Toulouse, France
| | | | | | | | | | - Ciprian Pricopi
- Hôpital Européen Georges-Pompidou, Université Paris-Descartes, Paris, France
| | - Jérôme Le Pavec
- Hôpital Marie-Lannelongue, Université Paris-Sud, Le Plessis Robinson, France
| | - Hervé Mal
- Hôpital Bichat, Université Paris-Diderot, INSERM 1152, Paris, France
| | | | - Romain Kessler
- Nouvel Hôpital Civil, CHU de Strasbourg, Strasbourg, France
| | - Antoine Roux
- Hôpital Foch, Université Versailles-Saint-Quentin, Suresnes, France
| | | | - Gabriel Thabut
- Hôpital Bichat, Université Paris-Diderot, INSERM 1152, Paris, France
| | - Pierre Mordant
- Hôpital Bichat, Université Paris-Diderot, INSERM 1152, Paris, France
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Foroutan F, Friesen EL, Clark KE, Motaghi S, Zyla R, Lee Y, Kamran R, Ali E, De Snoo M, Orchanian-Cheff A, Ribic C, Treleaven DJ, Guyatt G, Meade MO. Risk Factors for 1-Year Graft Loss After Kidney Transplantation: Systematic Review and Meta-Analysis. Clin J Am Soc Nephrol 2019; 14:1642-1650. [PMID: 31540931 PMCID: PMC6832056 DOI: 10.2215/cjn.05560519] [Citation(s) in RCA: 64] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Accepted: 08/05/2019] [Indexed: 01/15/2023]
Abstract
BACKGROUND AND OBJECTIVES With expansion of the pool of kidney grafts, through the use of higher-risk donors, and increased attention to donor management strategies, the 1-year graft survival rate is subject to change. It is, therefore, useful to elucidate 1-year graft survival rates by dissecting the characteristics of the low-risk and high-risk kidney transplant cases. The objective of our study was to evaluate factors purported to influence the risk of 1-year graft loss in kidney transplant recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We searched bibliographic databases from 2000 to 2017 and included observational studies that measured the association between donor, recipient, the transplant operation, or early postoperative complications, and 1-year death-censored graft loss. RESULTS We identified 35 eligible primary studies, with 20 risk factors amenable to meta-analysis. Six factors were associated with graft loss, with moderate to high degree of certainty: donor age (hazard ratio [HR], 1.11 per 10-year increase; 95% confidence interval [95% CI], 1.04 to 1.18), extended criteria donors (HR, 1.35; 95% CI, 1.28 to 1.42), deceased donors (HR, 1.54; 95% CI, 1.32 to 1.82), number of HLA mismatches (HR, 1.08 per one mismatch increase; 95% CI, 1.07 to 1.09), recipient age (HR, 1.17 per 10-year increase; 95% CI, 1.09 to 1.25), and delayed graft function (HR, 1.89; 95% CI, 1.46 to 2.47) as risk factors for 1-year graft loss. Pooled analyses also excluded, with a high degree of certainty, any associations of cold ischemia time, recipient race, pretransplant body mass index, diabetes, and hypertension with 1-year graft loss. CONCLUSIONS Recipient age, donor age, standard versus extended criteria donor, living versus deceased donor, HLA mismatch, and delayed graft function all predicted 1-year graft survival. The effect of each risk factor is small.
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Affiliation(s)
- Farid Foroutan
- Ted Rogers Centre for Heart Research, Multi-Organ Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
- Department of Health Research Methods, Evidence, and Impact and
| | - Erik Loewen Friesen
- Library and Information Services, University Health Network, Toronto, Ontario, Canada
| | - Kathryn Elizabeth Clark
- Ted Rogers Centre for Heart Research, Multi-Organ Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | | | - Roman Zyla
- Library and Information Services, University Health Network, Toronto, Ontario, Canada
| | - Yung Lee
- Department of Health Research Methods, Evidence, and Impact and
| | - Rakhshan Kamran
- Department of Health Research Methods, Evidence, and Impact and
| | - Emir Ali
- Department of Health Research Methods, Evidence, and Impact and
| | - Mitch De Snoo
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada; and
| | | | - Christine Ribic
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada; and
| | - Darin J. Treleaven
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada; and
| | - Gordon Guyatt
- Department of Health Research Methods, Evidence, and Impact and
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Ceresa CDL, Nasralla D, Watson CJE, Butler AJ, Coussios CC, Crick K, Hodson L, Imber C, Jassem W, Knight SR, Mergental H, Ploeg RJ, Pollok JM, Quaglia A, Shapiro AMJ, Weissenbacher A, Friend PJ. Transient Cold Storage Prior to Normothermic Liver Perfusion May Facilitate Adoption of a Novel Technology. Liver Transpl 2019; 25:1503-1513. [PMID: 31206217 DOI: 10.1002/lt.25584] [Citation(s) in RCA: 66] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Accepted: 05/16/2019] [Indexed: 12/12/2022]
Abstract
Clinical adoption of normothermic machine perfusion (NMP) may be facilitated by simplifying logistics and reducing costs. This can be achieved by cold storage of livers for transportation to recipient centers before commencing NMP. The purpose of this study was to assess the safety and feasibility of post-static cold storage normothermic machine perfusion (pSCS-NMP) in liver transplantation. In this multicenter prospective study, 31 livers were transplanted. The primary endpoint was 30-day graft survival. Secondary endpoints included the following: peak posttransplant aspartate aminotransferase (AST), early allograft dysfunction (EAD), postreperfusion syndrome (PRS), adverse events, critical care and hospital stay, biliary complications, and 12-month graft survival. The 30-day graft survival rate was 94%. Livers were preserved for a total of 14 hours 10 minutes ± 4 hours 46 minutes, which included 6 hours 1 minute ± 1 hour 19 minutes of static cold storage before 8 hours 24 minutes ± 4 hours 4 minutes of NMP. Median peak serum AST in the first 7 days postoperatively was 457 U/L (92-8669 U/L), and 4 (13%) patients developed EAD. PRS was observed in 3 (10%) livers. The median duration of initial critical care stay was 3 days (1-20 days), and median hospital stay was 13 days (7-31 days). There were 7 (23%) patients who developed complications of grade 3b severity or above, and 2 (6%) patients developed biliary complications: 1 bile leak and 1 anastomotic stricture with no cases of ischemic cholangiopathy. The 12-month overall graft survival rate (including death with a functioning graft) was 84%. In conclusion, this study demonstrates that pSCS-NMP was feasible and safe, which may facilitate clinical adoption.
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Affiliation(s)
- Carlo D L Ceresa
- Nuffield Department of Surgical Sciences, Oxford Transplant Centre, Churchill Hospital, University of Oxford, Oxford, United Kingdom
| | - David Nasralla
- Nuffield Department of Surgical Sciences, Oxford Transplant Centre, Churchill Hospital, University of Oxford, Oxford, United Kingdom
| | - Christopher J E Watson
- Department of Surgery, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom
| | - Andrew J Butler
- Department of Surgery, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom
| | - Constantin C Coussios
- Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, United Kingdom
| | - Keziah Crick
- Department of Surgery, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom
| | - Leanne Hodson
- Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom
| | - Charles Imber
- Department of Hepatopancreatobiliary and Liver Transplant Surgery, Royal Free Hospital, London, United Kingdom
| | - Wayel Jassem
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Simon R Knight
- Nuffield Department of Surgical Sciences, Oxford Transplant Centre, Churchill Hospital, University of Oxford, Oxford, United Kingdom
| | - Hynek Mergental
- Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom
| | - Rutger J Ploeg
- Nuffield Department of Surgical Sciences, Oxford Transplant Centre, Churchill Hospital, University of Oxford, Oxford, United Kingdom
| | - Joerg M Pollok
- Department of Hepatopancreatobiliary and Liver Transplant Surgery, Royal Free Hospital, London, United Kingdom
| | - Alberto Quaglia
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - A M James Shapiro
- Department of Surgery, University of Alberta, Edmonton, Alberta, Canada
| | - Annemarie Weissenbacher
- Nuffield Department of Surgical Sciences, Oxford Transplant Centre, Churchill Hospital, University of Oxford, Oxford, United Kingdom
| | - Peter J Friend
- Nuffield Department of Surgical Sciences, Oxford Transplant Centre, Churchill Hospital, University of Oxford, Oxford, United Kingdom
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Udomsin K, Lapisatepun W, Chotirosniramit A, Sandhu T, Ariyakachon V, Lorsomradee S, Boonsri S, Chanthima P, Lapisatepun W, Kaewpoowat Q, Ko-Iam W, Mueangin S, Chongruksut W, Junrungsee S. Adult-to-Adult Living Donor Liver Transplantation: Postoperative Outcomes and Quality of Life in Liver Donors: First Report in Thailand. Transplant Proc 2019; 51:2761-2765. [PMID: 31493914 DOI: 10.1016/j.transproceed.2019.03.080] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2019] [Accepted: 03/12/2019] [Indexed: 11/28/2022]
Abstract
BACKGROUND Deceased donor liver transplantation is a rare procedure in Northern Thailand because of cultural issues. Living donor liver transplantation (LDLT) can decrease waiting list mortality for the patients who have end-stage liver disease. In Thailand, our center is the only active adult-to-adult LDLT program. This study is the first report of outcomes and health-related quality of life in liver donors. OBJECTIVES The aim of this study was to evaluate the postoperative outcomes and health related quality of life in living liver transplant donors at the Transplant Center in Thailand. MATERIALS AND METHODS All patients undergoing liver resection for adult-to-adult LDLT at our center between March 2010 and July 2018 were evaluated in a cross-sectional study. The effect of donor demographics, operative details, postoperative complications (Clavien-Dindo classification), hospitalization, and health related quality of life was evaluated through health-related quality of life questionnaires (short-form survey, SF-36) RESULTS: A total of 14 donor patients were included in this study with an age range from 26 to 51 years (mean 39.86 years, standard deviation [SD] = 8.59 years). The patients were 71.43% female and 28.57% male. The majority of patients had primary and secondary education (57.14%) and were married (64.29%). After hepatectomy, there was no mortality in the evaluated donors. The Clavien-Dindo classification of postoperative complications were as follows: Grade I (none), Grade II (50%), Grade IIIa (7.14%), and Grade IIIb (7.14%). The serum levels of total protein and albumin were decreased on postoperative day 5. The hospital stays averaged 11.5 days (SD = 4.9 days) and ranged from 5 to 22 days. After considering each aspect of the donors' postoperative quality of life, the highest mean score was related to physical composite scores in physical roles with a mean of 96.42 (SD = 13.36) and physical function with a mean of 95.35 (SD = 13.36). Moreover, the mental composite scores in social function was the highest mean of 91.96 (SD = 12.60) and role emotion was a mean of 90.47 (SD = 27.51). CONCLUSIONS Living donor hepatectomy was safe, with an acceptable morbidity, and recognized as a safe procedure with an excellent long-term health quality of life.
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Affiliation(s)
- Kanya Udomsin
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Worakitti Lapisatepun
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Anon Chotirosniramit
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Trichak Sandhu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Veeravorn Ariyakachon
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Suraphong Lorsomradee
- Department of Anesthesiology Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Settapong Boonsri
- Department of Anesthesiology Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Phuriphong Chanthima
- Department of Anesthesiology Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Warangkana Lapisatepun
- Department of Anesthesiology Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Quanhathai Kaewpoowat
- Division of Infectious and Tropical Medicine, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Thailand
| | - Wasana Ko-Iam
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Sudarut Mueangin
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Wilaiwan Chongruksut
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Sunhawit Junrungsee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
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Ng VL, Mazariegos GV, Kelly B, Horslen S, McDiarmid SV, Magee JC, Loomes KM, Fischer RT, Sundaram SS, Lai JC, Te HS, Bucuvalas JC. Barriers to ideal outcomes after pediatric liver transplantation. Pediatr Transplant 2019; 23:e13537. [PMID: 31343109 DOI: 10.1111/petr.13537] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Revised: 06/03/2019] [Accepted: 06/11/2019] [Indexed: 12/13/2022]
Abstract
Long-term survival for children who undergo LT is now the rule rather than the exception. However, a focus on the outcome of patient or graft survival rates alone provides an incomplete and limited view of life for patients who undergo LT as an infant, child, or teen. The paradigm has now appropriately shifted to opportunities focused on our overarching goals of "surviving and thriving" with long-term allograft health, freedom of complications from long-term immunosuppression, self-reported well-being, and global functional health. Experts within the liver transplant community highlight clinical gaps and potential barriers at each of the pretransplant, intra-operative, early-, medium-, and long-term post-transplant stages toward these broader mandates. Strategies including clinical research, innovation, and quality improvement targeting both traditional as well as PRO are outlined and, if successfully leveraged and conducted, would improve outcomes for recipients of pediatric LT.
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Affiliation(s)
- Vicky Lee Ng
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Transplant and Regenerative Medicine Center, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
| | - George V Mazariegos
- Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania
| | - Beau Kelly
- Division of Surgery, DCI Donor Services, Sacramento, California
| | - Simon Horslen
- Department of Pediatrics, University of Washington, Seattle, Washington
| | - Sue V McDiarmid
- David Geffen School of Medicine, University of California, Los Angeles, California, USA
| | - John C Magee
- Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan
| | - Kathleen M Loomes
- Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Ryan T Fischer
- Division of Gastroenterology, Hepatology and Nutrition, Children's Mercy Hospital, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri
| | - Shikha S Sundaram
- Pediatrics, Gastroenterology, Hepatology and Nutrition, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado
| | - Jennifer C Lai
- Division of Gastroenterology/Hepatology, Department of Medicine, University of California, San Francisco, San Francisco, California
| | - Helen S Te
- Adult Liver Transplant Program, University of Chicago Medicine, Chicago, Illinois
| | - John C Bucuvalas
- Mount Sinai Kravis Childrens Hospital and Recanati/Miller Transplant Institute, New York City, New York
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Domagala P, Takagi K, Ijzermans JN, Polak WG. Grafts from selected deceased donors over 80 years old can safely expand the number of liver transplants: A systematic review and meta-analysis. Transplant Rev (Orlando) 2019; 33:209-218. [PMID: 31303351 DOI: 10.1016/j.trre.2019.06.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Revised: 06/23/2019] [Accepted: 06/28/2019] [Indexed: 12/20/2022]
Abstract
AIM The aim of this systematic review and meta-analysis was to present the outcome of deceased adult liver transplantation from octogenarian (≥80 years old) donors compared to younger grafts. METHODS A systematic search was performed on six databases to identify all available original papers that report the outcome of adult recipients who underwent liver transplantation from a deceased octogenarian donor. RESULTS Overall, 39,034 liver transplantations from 12 studies were reported with 789 (2.02%) cases receiving grafts from octogenarian donors. Eight studies were included in the meta-analysis. There was no difference regarding the one, three, and five-year graft and patient survival between the recipients of livers <80 years old and octogenarian grafts. There were significantly more episodes of biliary complications in the recipients of octogenarian grafts (34/459; 7.4%) in comparison to the recipients of livers <80 years old (372/37074; 1.0%) (OR 0.53; 95% CI = 0.35-0.81; P 0.004; I2 = 0%). The incidence of primary non-function, vascular complications and re-transplantation did not differ between groups. CONCLUSIONS The short- and medium-term graft and patient survival of octogenarian liver transplantation is not inferior compared to the liver transplantation with younger grafts, however with a higher rate of biliary complications.
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Affiliation(s)
- Piotr Domagala
- Erasmus MC, University Medical Centre Rotterdam, Department of Surgery, Division of HPB & Transplant Surgery, Dr. Molewaterplein 40, 3015, GD, Rotterdam, the Netherlands; The Medical University of Warsaw, Department of General and Transplantation Surgery, Nowogrodzka 59 St, 02-006 Warsaw, Poland.
| | - Kosei Takagi
- Erasmus MC, University Medical Centre Rotterdam, Department of Surgery, Division of HPB & Transplant Surgery, Dr. Molewaterplein 40, 3015, GD, Rotterdam, the Netherlands; Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Department of Gastroenterological Surgery, 2-5-1 Shikatacho, Kita-ku, Okayama-shi, Okayama, Japan
| | - Jan N Ijzermans
- Erasmus MC, University Medical Centre Rotterdam, Department of Surgery, Division of HPB & Transplant Surgery, Dr. Molewaterplein 40, 3015, GD, Rotterdam, the Netherlands.
| | - Wojciech G Polak
- Erasmus MC, University Medical Centre Rotterdam, Department of Surgery, Division of HPB & Transplant Surgery, Dr. Molewaterplein 40, 3015, GD, Rotterdam, the Netherlands.
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Santopaolo F, Lenci I, Milana M, Manzia TM, Baiocchi L. Liver transplantation for hepatocellular carcinoma: Where do we stand? World J Gastroenterol 2019; 25:2591-2602. [PMID: 31210712 PMCID: PMC6558441 DOI: 10.3748/wjg.v25.i21.2591] [Citation(s) in RCA: 77] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Revised: 04/09/2019] [Accepted: 04/29/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma represents an important cause of morbidity and mortality worldwide. It is the sixth most common cancer and the fourth leading cause of cancer death. Liver transplantation is a key tool for the treatment of this disease in human therefore hepatocellular carcinoma is increasing as primary indication for grafting. Although liver transplantation represents an outstanding therapy for hepatocellular carcinoma, due to organ shortage, the careful selection and management of patients who may have a major survival benefit after grafting remains a fundamental question. In fact, only some stages of the disease seem amenable of this therapeutic option, stimulating the debate on the appropriate criteria to select candidates. In this review we focused on current criteria to select patients with hepatocellular carcinoma for liver transplantation as well as on the strategies (bridging) to avoid disease progression and exclusion from grafting during the stay on wait list. The treatments used to bring patients within acceptable criteria (down-staging), when their tumor burden exceeds the standard criteria for transplant, are also reported. Finally, we examined tumor reappearance following liver transplantation. This occurrence is estimated to be approximately 8%-20% in different studies. The possible approaches to prevent this outcome after transplant are reported with the corresponding results.
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Affiliation(s)
- Francesco Santopaolo
- Hepatology Unit, Department of Medicine, Policlinico Universitario Tor Vergata, Rome 00133, Italy
| | - Ilaria Lenci
- Hepatology Unit, Department of Medicine, Policlinico Universitario Tor Vergata, Rome 00133, Italy
| | - Martina Milana
- Hepatology Unit, Department of Medicine, Policlinico Universitario Tor Vergata, Rome 00133, Italy
| | - Tommaso Maria Manzia
- Transplant Surgery Unit, Department of Surgery, Policlinico Universitario Tor Vergata, Rome 00133, Italy
| | - Leonardo Baiocchi
- Hepatology Unit, Department of Medicine, Policlinico Universitario Tor Vergata, Rome 00133, Italy
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49
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The Use of Donation After Circulatory Death Organs for Simultaneous Liver-kidney Transplant: To DCD or Not to DCD? Transplantation 2019; 103:1159-1167. [DOI: 10.1097/tp.0000000000002434] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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50
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Abstract
BACKGROUND Nonalcoholic steatohepatitis (NASH) cirrhosis is a common indication for liver transplantation (LT) in the United States. There is a paucity of data on retransplantation (re-LT) in those who were initially transplanted for NASH. METHODS We queried the United Network for Organ Sharing data sets from 2002 to 2016 to analyze the outcomes of adults with NASH (n = 128) and compared them with groups that received re-LT for cryptogenic cirrhosis (n = 189), alcoholic cirrhosis (n = 300) or autoimmune hepatitis cirrhosis (n = 118) after excluding multiple-organ re-LT and individuals with hepatocellular carcinoma. We estimated survival probabilities using a Kaplan-Meier estimator, and a relative risk of patient and graft mortality using proportional hazards regression. RESULTS The NASH group was older and had a higher prevalence of obesity, type II diabetes mellitus, renal insufficiency, portal vein thrombosis, and poor performance status. The median interval between the first and the second LT was shorter in the NASH group (27 days). The graft and patient 5-year survival rates were lower for the NASH group after re-LT compared with the other 3 groups. After adjusting for demographic and disease complication factors, the factors that increased a risk of patient or graft failure were a poor performance status (hazard ratio [HR], 1.64; 1.19-2.26), Donor Risk Index (HR, 1.51; 1.08-2.12), and a high Model for End-stage Liver Disease score (HR, 1.02; 1.00-1.04). CONCLUSIONS Despite the comparable outcomes reported for initial LT among the various etiologies, the outcome of re-LT is significantly worse for NASH cirrhosis.
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