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1
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Ghanem OM, Pita A, Nazzal M, Johnson S, Diwan T, Obeid NR, Croome KP, Lim R, Quintini C, Whitson BA, Burt HA, Miller C, Kroh M. Obesity, organ failure, and transplantation: A review of the role of metabolic and bariatric surgery in transplant candidates and recipients. Am J Transplant 2024; 24:1534-1546. [PMID: 38951053 DOI: 10.1016/j.ajt.2024.04.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 03/16/2024] [Accepted: 04/03/2024] [Indexed: 07/03/2024]
Abstract
Obesity is a risk factor for kidney, liver, heart, and pulmonary diseases, as well as failure. Solid organ transplantation remains the definitive treatment for the end-stage presentation of these diseases. Among many criteria for organ transplant, efficient management of obesity is required for patients to acquire transplant eligibility. End-stage organ failure and obesity are 2 complex pathologies that are often entwined. Metabolic and bariatric surgery before, during, or after organ transplant has been studied to determine the long-term effect of bariatric surgery on transplant outcomes. In this review, a multidisciplinary group of surgeons from the Society of American Gastrointestinal and Endoscopic Surgeons and the American Society for Transplant Surgery presents the current published literature on metabolic and bariatric surgery as a therapeutic option for patients with obesity awaiting solid organ transplantation. This manuscript details the most recent recommendations, pharmacologic considerations, and psychological considerations for this specific cohort of patients. Since level one evidence is not available on many of the topics covered by this review, expert opinion was implemented in several instances. Additional high-quality research in this area will allow for better recommendations and, therefore, treatment strategies for these complex patients.
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Affiliation(s)
- Omar M Ghanem
- Department of Surgery, Mayo Clinic Rochester, Minnesota, USA.
| | - Alejandro Pita
- Department of Surgery, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Mustafa Nazzal
- Department of Surgery, Saint Louis University Hospital, St. Louis, Missouri, USA
| | - Shaneeta Johnson
- Department of Surgery, Morehouse School of Medicine, Atlanta, Georgia, USA
| | - Tayyab Diwan
- Department of Surgery, Mayo Clinic Rochester, Minnesota, USA
| | - Nabeel R Obeid
- Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA
| | | | - Robert Lim
- Atrium Health Carolinas Medical Center, Wake Forest University School of Medicine, Charlotte, North Carolina, USA
| | - Cristiano Quintini
- Digestive Disease Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - Bryan A Whitson
- Department of Surgery, Division of Cardiac Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Holly Ann Burt
- Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), Los Angeles, California, USA
| | - Charles Miller
- Department of Surgery, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Matthew Kroh
- Department of Surgery, Cleveland Clinic Foundation, Cleveland, Ohio, USA
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Berg T, Aehling NF, Bruns T, Welker MW, Weismüller T, Trebicka J, Tacke F, Strnad P, Sterneck M, Settmacher U, Seehofer D, Schott E, Schnitzbauer AA, Schmidt HH, Schlitt HJ, Pratschke J, Pascher A, Neumann U, Manekeller S, Lammert F, Klein I, Kirchner G, Guba M, Glanemann M, Engelmann C, Canbay AE, Braun F, Berg CP, Bechstein WO, Becker T, Trautwein C. S2k-Leitlinie Lebertransplantation der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) und der Deutschen Gesellschaft für Allgemein- und Viszeralchirurgie (DGAV). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1397-1573. [PMID: 39250961 DOI: 10.1055/a-2255-7246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/11/2024]
Affiliation(s)
- Thomas Berg
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Niklas F Aehling
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Tony Bruns
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martin-Walter Welker
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin. Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Tobias Weismüller
- Klinik für Innere Medizin - Gastroenterologie und Hepatologie, Vivantes Humboldt-Klinikum, Berlin, Deutschland
| | - Jonel Trebicka
- Medizinische Klinik B für Gastroenterologie und Hepatologie, Universitätsklinikum Münster, Münster, Deutschland
| | - Frank Tacke
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Pavel Strnad
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martina Sterneck
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - Utz Settmacher
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Jena, Deutschland
| | - Daniel Seehofer
- Klinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Eckart Schott
- Klinik für Innere Medizin II - Gastroenterologie, Hepatologie und Diabetolgie, Helios Klinikum Emil von Behring, Berlin, Deutschland
| | | | - Hartmut H Schmidt
- Klinik für Gastroenterologie und Hepatologie, Universitätsklinikum Essen, Essen, Deutschland
| | - Hans J Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg, Regensburg, Deutschland
| | - Johann Pratschke
- Chirurgische Klinik, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Andreas Pascher
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Münster, Münster, Deutschland
| | - Ulf Neumann
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen, Essen, Deutschland
| | - Steffen Manekeller
- Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Bonn, Deutschland
| | - Frank Lammert
- Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - Ingo Klein
- Chirurgische Klinik I, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Gabriele Kirchner
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg und Innere Medizin I, Caritaskrankenhaus St. Josef Regensburg, Regensburg, Deutschland
| | - Markus Guba
- Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie, Universitätsklinikum München, München, Deutschland
| | - Matthias Glanemann
- Klinik für Allgemeine, Viszeral-, Gefäß- und Kinderchirurgie, Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - Cornelius Engelmann
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Ali E Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - Felix Braun
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
| | - Christoph P Berg
- Innere Medizin I Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - Wolf O Bechstein
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Thomas Becker
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
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Schmidt K, Spann A, Khan MQ, Izzy M, Watt KD. Minimizing Metabolic and Cardiac Risk Factors to Maximize Outcomes After Liver Transplantation. Transplantation 2024; 108:1689-1699. [PMID: 38060378 DOI: 10.1097/tp.0000000000004875] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/24/2024]
Abstract
Cardiovascular disease (CVD) is a leading complication after liver transplantation and has a significant impact on patients' outcomes posttransplant. The major risk factors for post-liver transplant CVD are age, preexisting CVD, nonalcoholic fatty liver disease, chronic kidney disease, and metabolic syndrome. This review explores the contemporary strategies and approaches to minimizing cardiometabolic disease burden in liver transplant recipients. We highlight areas for potential intervention to reduce the mortality of patients with metabolic syndrome and CVD after liver transplantation.
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Affiliation(s)
- Kathryn Schmidt
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Ashley Spann
- Division of Gastroenterology and Hepatology, Vanderbilit University, Nashville, TN
| | - Mohammad Qasim Khan
- Division of Gastroenterology and Hepatology, University of Western Ontario, London, ON, Canada
| | - Manhal Izzy
- Division of Gastroenterology and Hepatology, Vanderbilit University, Nashville, TN
| | - Kymberly D Watt
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
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Ghanem OM, Pita A, Nazzal M, Johnson S, Diwan T, Obeid NR, Croome KP, Lim R, Quintini C, Whitson BA, Burt HA, Miller C, Kroh M. Obesity, organ failure, and transplantation: a review of the role of metabolic and bariatric surgery in transplant candidates and recipients. Surg Endosc 2024; 38:4138-4151. [PMID: 38951240 PMCID: PMC11289013 DOI: 10.1007/s00464-024-10930-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Accepted: 04/03/2024] [Indexed: 07/03/2024]
Abstract
Obesity is a risk factor for kidney, liver, heart, and pulmonary diseases, as well as failure. Solid organ transplantation remains the definitive treatment for the end-stage presentation of these diseases. Among many criteria for organ transplant, efficient management of obesity is required for patients to acquire transplant eligibility. End-stage organ failure and obesity are 2 complex pathologies that are often entwined. Metabolic and bariatric surgery before, during, or after organ transplant has been studied to determine the long-term effect of bariatric surgery on transplant outcomes. In this review, a multidisciplinary group of surgeons from the Society of American Gastrointestinal and Endoscopic Surgeons and the American Society for Transplant Surgery presents the current published literature on metabolic and bariatric surgery as a therapeutic option for patients with obesity awaiting solid organ transplantation. This manuscript details the most recent recommendations, pharmacologic considerations, and psychological considerations for this specific cohort of patients. Since level one evidence is not available on many of the topics covered by this review, expert opinion was implemented in several instances. Additional high-quality research in this area will allow for better recommendations and, therefore, treatment strategies for these complex patients.
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Affiliation(s)
- Omar M Ghanem
- Department of Surgery, Mayo Clinic Rochester, Rochester, MN, USA.
| | - Alejandro Pita
- Department of Surgery, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Mustafa Nazzal
- Department of Surgery, Saint Louis University Hospital, St. Louis, MO, USA
| | - Shaneeta Johnson
- Department of Surgery, Morehouse School of Medicine, Atlanta, GA, USA
| | - Tayyab Diwan
- Department of Surgery, Mayo Clinic Rochester, Rochester, MN, USA
| | - Nabeel R Obeid
- Department of Surgery, University of Michigan, Ann Arbor, MI, USA
| | | | - Robert Lim
- Atrium Health Carolinas Medical Center, Wake Forest University School of Medicine, Charlotte, NC, USA
| | - Cristiano Quintini
- Digestive Disease Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - Bryan A Whitson
- Division of Cardiac Surgery, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Holly Ann Burt
- Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), Los Angeles, CA, USA
| | - Charles Miller
- Department of Surgery, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Matthew Kroh
- Department of Surgery, Cleveland Clinic Foundation, Cleveland, OH, USA
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Flynn SJ, Saxena V, Brandman D. Primary Care Utilization, Preventative Screening, and Control of Metabolic Syndrome in Metabolic Dysfunction-Associated Steatohepatitis Liver Transplant Recipients. J Prim Care Community Health 2024; 15:21501319241247974. [PMID: 38650519 PMCID: PMC11036922 DOI: 10.1177/21501319241247974] [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: 02/03/2024] [Revised: 03/25/2024] [Accepted: 03/29/2024] [Indexed: 04/25/2024] Open
Abstract
OBJECTIVES Patients with pre-transplant metabolic dysfunction-associated steatohepatitis (MASH) are at high risk of metabolic syndrome (MetS) after liver transplant. While many patients are co-managed by a transplant team, most preventative screening and MetS management may occur in the primary care setting. We aimed to evaluate primary care utilization by MASH liver transplant recipients as well as MetS screening and control. METHODS We conducted a retrospective chart review that included adults who underwent liver transplant for MASH or cryptogenic cirrhosis at a single institution from January 2010 to December 2016, had available primary care data, and at least 36-months of follow-up post-transplant. Measures included primary care utilization, adherence to screening guidelines, and control of MetS. We used Fischer's exact test to explore the association of primary care utilization with screening and control. RESULTS A total of 37 patients met inclusion criteria with 366 visits reviewed. The median time to first visit was 68 days post-transplant and patients had a median of 9 total visits. Few patients met screening guidelines for diabetes (8.1%) or hyperlipidemia (10.8%). The percentage of patients with control of obesity, hypertension, diabetes, and hyperlipidemia decreased over the 36-month follow-up period. Primary care utilization was not associated with adherence to screening recommendations for diabetes (P = .141) or hyperlipidemia (P = .103). Higher primary care utilization was not associated with control of hypertension (P = .107), diabetes (P = .871), or hyperlipidemia (P = .999). CONCLUSION More research is needed to investigate barriers to screening and management of MetS conditions in this high-risk patient population in the primary care setting as well as to optimize post-transplant care coordination.
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Affiliation(s)
| | - Varun Saxena
- Kaiser Permanente South San Francisco Medical Center, San Francisco, CA, USA
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So BN, Reddy KR. Liver Transplantation for the Nonhepatologist. Med Clin North Am 2023; 107:605-621. [PMID: 37001956 DOI: 10.1016/j.mcna.2023.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/22/2023]
Abstract
Liver transplantation (LT) is a life-saving and evidence-based intervention for patients with acute liver failure and chronic end-stage liver disease. Significant progress has been made in advancing pre-LT management, transplant techniques, post-LT long-term care, and immunosuppression regimes. However, as rates of DC continue to increase, causes of liver disease and indications for LT continue to be investigated to ensure equity and further improve liver allocation models, waitlist outcomes, and post-LT outcomes for all patient populations.
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Affiliation(s)
- Bethany Nahri So
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, University of Pennsylvania, 2 Dulles, 3400 Spruce Street, HUP, Philadelphia, PA 19104, USA.
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Salman AA, Salman MA, Said M, Elkassar H, El Sherbiny M, Youssef A, Elbaz M, Elmeligui AM, Hassan MB, Omar MG, Samir H, Abdelkader Morad M, Shaaban HED, Youssef M, Moustafa A, Tourky MS, Elewa A, Khalid S, Monazea K, Shawkat M. Albuminuria as a predictor of mortality in type II diabetic patients after living-donor liver transplantation. Ann Med 2022; 54:2598-2605. [PMID: 36164711 PMCID: PMC9521493 DOI: 10.1080/07853890.2022.2124446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 09/02/2022] [Accepted: 09/08/2022] [Indexed: 11/01/2022] Open
Abstract
PURPOSE Diabetes mellitus (DM) increases the risk of morbidity and mortality after liver resection. Albuminuria is associated with a higher risk for all-cause and cardiovascular mortality. This study evaluated albuminuria as a predictor of the outcome of living donor liver transplantation (LDLT) in patients with pre-existing DM. METHODS This retrospective study involved 103 type II diabetic patients with end-stage liver disease who received LDLT. Preoperative spot urine albumin: creatinine ratio was used to determine the degree of albuminuria. The primary outcome measure was the impact of urinary albumin excretion on the 3-year mortality rate after LDLT in this diabetic cohort. RESULTS Hepatitis C virus infection was the main cause of cirrhosis. Albuminuria was detected in 41 patients (39.8%); 15 had macroalbuminuria, while 26 had microalbuminuria. Patients with microalbuminuria were significantly older than those with macroalbuminuria and normal albumin in urine. After 3 years, twenty-four patients (23.3%) died within 3 years after LT. Myocardial infarction was the leading cause of death (25%). Albuminuria was an independent factor affecting 3-year mortality with an odds ratio of 5.17 (95% CI: 1.86-14.35). CONCLUSION Preoperative albuminuria is an independent factor affecting mortality within 3 years after LDLT in type II diabetic patients. Myocardial infarction was the leading cause of death in 25% of cases, followed by hepatocellular carcinoma recurrence, sepsis, and graft failure.KEY MESSAGESDiabetes mellitus (DM) increases the risk of morbidity and mortality after liver resection.Albuminuria is associated with a higher risk for all-cause and cardiovascular mortality.Preoperative albuminuria is a significant predictor of mortality within 3 years after LDLT in diabetic patients.
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Affiliation(s)
| | | | - Mostafa Said
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hesham Elkassar
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohammad El Sherbiny
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Youssef
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohammed Elbaz
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed M. Elmeligui
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed Badr Hassan
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mahmoud Gouda Omar
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hussien Samir
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | | | - Hossam El-Din Shaaban
- Gastroenterology Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Mohamed Youssef
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Moustafa
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed Sabry Tourky
- Department of Surgery, Great Western Hospitals NHS Foundation Trust, Swindon, UK
| | - Ahmed Elewa
- General Surgery Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Sadaf Khalid
- General Surgery Department, Royal Free Hospital, London, UK
| | - Khaled Monazea
- General Surgery Department, Assiut Faculty of Medicine for Boys, Al-Azhar University, Cairo, Egypt
| | - Mohamed Shawkat
- Internal Medicine Department, Faculty of Medicine, Minia University, Minia, Egypt
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8
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Lonardo A, Mantovani A, Petta S, Carraro A, Byrne CD, Targher G. Metabolic mechanisms for and treatment of NAFLD or NASH occurring after liver transplantation. Nat Rev Endocrinol 2022; 18:638-650. [PMID: 35840803 DOI: 10.1038/s41574-022-00711-5] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/07/2022] [Indexed: 11/08/2022]
Abstract
The rising tide of non-alcoholic fatty liver disease (NAFLD) associated with the obesity epidemic is a major health concern worldwide. NAFLD - specifically its more advanced form, non-alcoholic steatohepatitis (NASH)-related cirrhosis - is now the fastest growing indication for liver transplantation in the USA and Europe. Although the short-term and mid-term overall survival rates of patients who receive a liver transplant for NASH-related cirrhosis are essentially similar to those of patients who receive a transplant for other liver indications, recipients with NASH-related cirrhosis have an increased risk of waiting-list mortality and of developing recurrent liver disease and cardiometabolic complications in the longer term after liver transplantation. This Review provides a brief overview of the epidemiology of NAFLD and NASH and the occurrence of NAFLD or NASH in patients after liver transplantation for NASH and other liver indications. It also discusses the putative metabolic mechanisms underlying the emergence of NAFLD or NASH after liver transplantation as well as optimal therapeutic approaches for recipients of liver transplants, including the management of cardiometabolic comorbidities, tailored immunosuppression, lifestyle changes and pharmacotherapy for NAFLD.
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Affiliation(s)
- Amedeo Lonardo
- Metabolic Syndrome Unit, University of Modena, Modena, Italy
| | - Alessandro Mantovani
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona, Verona, Italy
| | - Salvatore Petta
- Section of Gastroenterology and Hepatology, PROMISE, University of Palermo, Palermo, Italy
| | - Amedeo Carraro
- Liver Transplant Unit, University of Verona, Verona, Italy
| | - Christopher D Byrne
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK
- Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Southampton, UK
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona, Verona, Italy.
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9
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Eshraghian A, Fattahi MR, Taghavi A, Shamsaeefar A, Mansoorian M, Kazemi K, Nikeghbalian S, Malek-Hosseini SA. Metabolic syndrome, hepatic fibrosis, and steatosis diagnosed by liver stiffness measurement and controlled attenuation parameter after liver transplantation: the impact on long-term survival. Expert Rev Gastroenterol Hepatol 2022; 16:1003-1009. [PMID: 36254767 DOI: 10.1080/17474124.2022.2137488] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
BACKGROUND Liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) are used for diagnosis of liver fibrosis and steatosis. This study aimed to noninvasively evaluate hepatic steatosis and fibrosis in liver transplant recipients using CAP and LSM and the impact on survival of patients. METHODS In a prospective study, adult liver transplant recipients were included. CAP and LSM obtained during transient elastography (TE) were used for assessment of hepatic steatosis and fibrosis. Patients were followed during 4 years for mortality as the main outcome after liver transplantation. RESULTS From 296 patients, 24.7% and 25% of liver transplant recipients had liver steatosis and fibrosis in CAP and LSM, respectively. In multivariable Cox regression analysis, etiology of liver disease (NASH versus non-NASH) (HR: 3.125; 95% CI: 1.594-6.134; p = 0.001), and post-transplant diabetes mellitus (PTDM) (HR: 2.617; 95% CI: 1.396-4.926; p = 0.003) were associated with hepatic steatosis after liver transplantation. In multivariable Cox regression analysis, liver fibrosis was an independent predictor of mortality after liver transplantation (HR: 4.926; 95%CI: 1.779-13.513; p = 0.002). CONCLUSION CAP and LS measurement during TE are useful methods for diagnosis of hepatic steatosis and fibrosis in liver transplant recipients. LS measurement might predict long-term survival of patients.
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Affiliation(s)
- Ahad Eshraghian
- Shiraz Transplant Center, Abu-Ali Sina Hospital, Shiraz, Iran
| | - Mohammad Reza Fattahi
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Alireza Taghavi
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Alireza Shamsaeefar
- Shiraz Transplant Center, Abu-Ali Sina Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohsenreza Mansoorian
- Shiraz Transplant Center, Abu-Ali Sina Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Kourosh Kazemi
- Shiraz Transplant Center, Abu-Ali Sina Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Saman Nikeghbalian
- Shiraz Transplant Center, Abu-Ali Sina Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Seyed Ali Malek-Hosseini
- Shiraz Transplant Center, Abu-Ali Sina Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
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10
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Garcia-Saenz-de-Sicilia M, Al-Obaid L, Hughes DL, Duarte-Rojo A. Mastering Core Recommendations during HEPAtology ROUNDS in Patients with Advanced Chronic Liver Disease. Semin Liver Dis 2022; 42:341-361. [PMID: 35764316 DOI: 10.1055/a-1886-5909] [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: 02/07/2023]
Abstract
Efficient and thorough care of hospitalized patients with advanced chronic liver disease is of utter importance to improve outcomes and optimize quality of life. This requires understanding current evidence and best practices. To facilitate focus on up-to-date knowledge and a practical approach, we have created the HEPA-ROUNDS mnemonic while outlining a practical review of the literature with critical appraisal for the busy clinician. The HEPA-ROUNDS mnemonic provides a structured approach that incorporates critical concepts in terms of prevention, management, and prognostication of the most common complications frequently encountered in patients with advanced chronic liver disease. In addition, implementing the HEPA-ROUNDS mnemonic can facilitate education for trainees and staff caring for patients with advanced chronic liver disease.
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Affiliation(s)
| | - Lolwa Al-Obaid
- Division of Gastroenterology, Washington University School of Medicine in St. Louis, St. Louis, Missouri
| | - Dempsey L Hughes
- Division of Gastroenterology, Hepatology and Nutrition, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Andrés Duarte-Rojo
- Division of Gastroenterology, Hepatology and Nutrition, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
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11
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Liver Transplantation in Recipients With Class III Obesity: Posttransplant Outcomes and Weight Gain. Transplant Direct 2022; 8:e1242. [PMID: 35018300 PMCID: PMC8735757 DOI: 10.1097/txd.0000000000001242] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 07/08/2021] [Accepted: 07/18/2019] [Indexed: 11/26/2022] Open
Abstract
Background. There has been a dramatic increase in obesity in the United States. Several studies have reported conflicting results for the impact of obesity on outcomes of liver transplantation (LT). This study aims to assess the impact of obesity on LT and changes in body mass index (BMI) after transplantation. Methods. All adult LTs performed at Indiana University between 2001 and 2018 were reviewed. BMIs of recipients were subdivided into 6 categories. Survival outcomes were compared across the subgroup. BMI was followed up in a cohort of patients from 2008 to 2018. Results. Among 2024 patients, 25% were in class I obesity, 9.3% were in class II obesity, and 1.1% were in class III obesity. There was no significant difference in patient and graft survival at 10-y follow-up with respect to BMI. Among 1004 patients in the subgroup, BMI of all groups except the underweight group declined in the first 3 mo postoperatively; however, the BMI of all groups except the class III obesity group returned to the pre-LT level by 2 y and reached a plateau by 5 y. In the class III obesity group, there was a significant increase in body weight at 5 y. Conclusions. Class III obesity was not associated with higher mortality in our cohort. Because our cohort is small, it may be underpowered to detect a smaller difference in outcome. From our observation, obesity should not be considered a contraindication for LT. Post-LT interventions are required to prevent significant weight gain for the class III obesity group.
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12
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Plaz MC, Tsochatzis EA. Metabolic Complications Before and After Liver Transplantation. TEXTBOOK OF LIVER TRANSPLANTATION 2022:357-371. [DOI: 10.1007/978-3-030-82930-8_20] [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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13
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Becchetti C, Ferrarese A, Zeni N, Russo FP, Senzolo M, Gambato M, Bassi D, Cillo U, Burra P, Germani G. A prospective longitudinal assessment of de novo metabolic syndrome after liver transplantation. Clin Transplant 2021; 36:e14532. [PMID: 34757678 DOI: 10.1111/ctr.14532] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Revised: 10/13/2021] [Accepted: 11/03/2021] [Indexed: 11/28/2022]
Abstract
BACKGROUND De novo metabolic syndrome (MS) is a frequent complication after liver transplantation (LT). The aim of this prospective study is to identify potential risk factors longitudinally associated to post-LT de novo MS. Patients without pre-LT MS who underwent LT between April 2013 and October 2017 were prospectively included. Metabolic variables were collected at LT and at 6, 12 and 24 months post-LT. RESULTS 63 patients fulfilled the inclusion criteria (76% male, mean age 53.6±9.5 years). The prevalence of de novo MS was 46%, 43% and 49% at 6, 12, and 24 months after LT respectively. Among other MS components, the prevalence of type 2 diabetes, hypertension and hypertriglyceridemia significantly increased after LT. Considering the baseline characteristics at the adjusted analysis, alcoholic liver disease (OR 4.17, 95%CI 1.20-14.51; p = 0.03) and hypertension pre-LT (OR 11.3, 95%CI 1.49-85.46; p = 0.02 were confirmed as independent risk factors of post-LT de novo MS. In the time varying analysis, only eGFR (OR 0.97, 95%IC 0.97-0.98; p<0.0001) was found associated with post-LT de novo MS. CONCLUSIONS De novo MS frequently occurs shortly after LT, affecting nearly half of patients at 24 months post-LT. Lifestyle modifications should be recommended starting early post-LT, particularly for patients with established risk factors. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Chiara Becchetti
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital Padua, University of Padua, Padua, Italy.,Hepatology, Department of Visceral Surgery and Medicine, Inselspital, Department of Biomedical Research, University Hospital Bern, University of Bern, Bern, Switzerland
| | - Alberto Ferrarese
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital Padua, University of Padua, Padua, Italy
| | - Nicola Zeni
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital Padua, University of Padua, Padua, Italy
| | - Francesco Paolo Russo
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital Padua, University of Padua, Padua, Italy
| | - Marco Senzolo
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital Padua, University of Padua, Padua, Italy
| | - Martina Gambato
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital Padua, University of Padua, Padua, Italy
| | - Domenico Bassi
- Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital Padua, University of Padua, Padua, Italy
| | - Giacomo Germani
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital Padua, University of Padua, Padua, Italy
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14
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Strategies to Improve Immune Suppression Post-Liver Transplantation: A Review. TRANSPLANTOLOGY 2021. [DOI: 10.3390/transplantology2040042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Since the first liver transplantation operation (LT) in 1967 by Thomas Starzl, efforts to increase survival and prevent rejection have taken place. The development of calcineurin inhibitors (CNIs) in the 1980s led to a surge in survival post-transplantation, and since then, strategies to prevent graft loss and preserve long-term graft function have been prioritized. Allograft rejection is mediated by the host immune response to donor antigens. Prevention of rejection can be achieved through either immunosuppression or induction of tolerance. This leads to a clinical dilemma, as the choice of an immunosuppressive agent is not an easy task, with considerable patient and graft-related morbidities. On the other hand, the induction of graft tolerance remains a challenge. Despite the fact that the liver exhibits less rejection than any other transplanted organs, spontaneous graft tolerance is rare. Most immunosuppressive medications have been incriminated in renal, cardiovascular, and neurological complications, relapse of viral hepatitis, and recurrence of HCC and other cancers. Efforts to minimize immunosuppression are directed toward decreasing medication side effects, increasing cost effectiveness, and decreasing economic burden without increasing the risk of rejection. In this article, we will discuss recent advances in strategies for improving immunosuppression following liver transplantation.
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15
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Koshy AN, Gow PJ, Han HC, Teh AW, Jones R, Testro A, Lim HS, McCaughan G, Jeffrey GP, Crawford M, Macdonald G, Fawcett J, Wigg A, Chen JWC, Gane EJ, Munn SR, Clark DJ, Yudi MB, Farouque O. Cardiovascular mortality following liver transplantation: predictors and temporal trends over 30 years. EUROPEAN HEART JOURNAL. QUALITY OF CARE & CLINICAL OUTCOMES 2021; 6:243-253. [PMID: 32011663 DOI: 10.1093/ehjqcco/qcaa009] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Revised: 01/21/2020] [Accepted: 01/24/2020] [Indexed: 12/13/2022]
Abstract
AIMS There has been significant evolution in operative and post-transplant therapies following liver transplantation (LT). We sought to study their impact on cardiovascular (CV) mortality, particularly in the longer term. METHODS AND RESULTS A retrospective cohort study was conducted of all adult LTs in Australia and New Zealand across three 11-year eras from 1985 to assess prevalence, modes, and predictors of early (≤30 days) and late (>30 days) CV mortality. A total of 4265 patients were followed-up for 37 409 person-years. Overall, 1328 patients died, and CV mortality accounted for 228 (17.2%) deaths. Both early and late CV mortality fell significantly across the eras (P < 0.001). However, CV aetiologies were consistently the leading cause of early mortality and accounted for ∼40% of early deaths in the contemporary era. Cardiovascular deaths occurred significantly later than non-cardiac aetiologies (8.8 vs. 5.2 years, P < 0.001). On multivariable Cox regression, coronary artery disease [hazard ratio (HR) 4.6, 95% confidence interval (CI) 1.2-21.6; P = 0.04] and era of transplantation (HR 0.44; 95% CI 0.28-0.70; P = 0.01) were predictors of early CV mortality, while advancing age (HR 1.05, 95% CI 1.02-1.10; P = 0.005) was an independent predictors of late CV mortality. Most common modes of CV death were cardiac arrest, cerebrovascular events, and myocardial infarction. CONCLUSION Despite reductions in CV mortality post-LT over 30 years, they still account for a substantial proportion of early and late deaths. The late occurrence of CV deaths highlights the importance of longitudinal follow-up to study the efficacy of targeted risk-reduction strategies in this unique patient population.
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Affiliation(s)
- Anoop N Koshy
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia.,The University of Melbourne, Parkville, Victoria, Australia
| | - Paul J Gow
- The University of Melbourne, Parkville, Victoria, Australia.,Victorian Liver Transplant Unit, Austin Hospital, Melbourne, Victoria, Australia
| | - Hui-Chen Han
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia.,The University of Melbourne, Parkville, Victoria, Australia
| | - Andrew W Teh
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia.,The University of Melbourne, Parkville, Victoria, Australia
| | - Robert Jones
- The University of Melbourne, Parkville, Victoria, Australia.,Victorian Liver Transplant Unit, Austin Hospital, Melbourne, Victoria, Australia
| | - Adam Testro
- The University of Melbourne, Parkville, Victoria, Australia.,Victorian Liver Transplant Unit, Austin Hospital, Melbourne, Victoria, Australia
| | - Han S Lim
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia.,The University of Melbourne, Parkville, Victoria, Australia
| | - Geoffrey McCaughan
- Department of Liver Transplantation, Royal Prince Alfred Hospital, Sydney, Australia.,University of Sydney, Sydney, Australia
| | - Gary P Jeffrey
- Department of Liver Transplantation, Sir Charles Gardiner Hospital, Perth, Australia.,School of Medicine, University of Western Australia, Nedlands, Australia
| | - Michael Crawford
- Department of Liver Transplantation, Royal Prince Alfred Hospital, Sydney, Australia.,University of Sydney, Sydney, Australia
| | - Graeme Macdonald
- Department of Liver Transplantation, Princess Alexandra Hospital, Brisbane, Australia.,School of Medicine, The University of Queensland, Brisbane, Australia
| | - Jonathan Fawcett
- Department of Liver Transplantation, Princess Alexandra Hospital, Brisbane, Australia.,School of Medicine, The University of Queensland, Brisbane, Australia
| | - Alan Wigg
- Department of Liver Transplantation, Flinders Medical Centre, Adelaide, Australia
| | - John W C Chen
- Department of Liver Transplantation, Flinders Medical Centre, Adelaide, Australia
| | | | | | - David J Clark
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia.,The University of Melbourne, Parkville, Victoria, Australia
| | - Matias B Yudi
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia.,The University of Melbourne, Parkville, Victoria, Australia
| | - Omar Farouque
- Department of Cardiology, Austin Health, Melbourne, Victoria, Australia.,The University of Melbourne, Parkville, Victoria, Australia
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16
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Sertić Z, Letilović T, Kanižaj TF, Knotek M, Hadžibegović I, Starovečki I, Jerkić H. Cardiovascular mortality in liver and kidney transplant recipients: A retrospective analysis from a single institution. Medicine (Baltimore) 2021; 100:e26019. [PMID: 34011105 PMCID: PMC8137067 DOI: 10.1097/md.0000000000026019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Accepted: 04/30/2021] [Indexed: 01/05/2023] Open
Abstract
Previous studies have demonstrated cardiovascular causes to be among the leading causes of death after liver (LT) and kidney transplantation (KT). Although both recipient populations have unique pre-transplant cardiovascular burdens, they share similarities in post-transplant exposure to cardiovascular risk factors. The aim of this study was to compare cardiovascular mortality after LT and KT.We analyzed causes of death in 370 consecutive LT and 207 KT recipients from in-hospital records at a single tertiary transplant center. Cardiovascular causes of death were defined as cardiac arrest, heart failure, pulmonary embolism, or myocardial infarction.After a median follow-up of 36.5 months, infection was the most common cause of death in both cohorts, followed by cardiovascular causes in KT recipients and graft-related causes in LT recipients in whom cardiovascular causes were the third most common. Cumulative incidence curves for cardiovascular mortality computed with death from other causes as the competing risk were not significantly different (P = .36). While 1-year cumulative cardiovascular mortality was similar (1.6% after LT and 1.5% after KT), the estimated 4-year probability was higher post-KT (3.8% vs. 1.6%). Significant pre-transplant risk factors for overall mortality after KT in multivariable analysis were age at transplantation, left ventricular ejection fraction <50%, and diastolic dysfunction grade 2 or greater, while significant risk factors for cardiovascular mortality were peripheral artery disease and left ventricular ejection fraction <50%. In the LT group no variables remained significant in a multivariable model for either overall or cardiovascular mortality.The present study found no significant overall difference in cardiovascular mortality after LT and KT. While LT and KT recipients may have similar early cardiovascular mortality, long-term risk is potentially lower after LT. Differing characteristics of cardiovascular death between these two patient populations should be further investigated.
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Affiliation(s)
- Zrinka Sertić
- Department of Emergency Medicine, University Hospital Centre Zagreb
| | - Tomislav Letilović
- Division of Cardiology, University Hospital Merkur
- School of Medicine, University of Zagreb
| | - Tajana Filipec Kanižaj
- School of Medicine, University of Zagreb
- Division of Gastroenterology, University Hospital Merkur, Zagreb, Croatia
| | | | - Irzal Hadžibegović
- Division of Cardiology, University Hospital Dubrava, Zagreb
- Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| | | | - Helena Jerkić
- Division of Cardiology, University Hospital Merkur
- School of Medicine, University of Zagreb
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17
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Welch N, Attaway A, Bellar A, Alkhafaji H, Vural A, Dasarathy S. Compound Sarcopenia in Hospitalized Patients with Cirrhosis Worsens Outcomes with Increasing Age. Nutrients 2021; 13:nu13020659. [PMID: 33670535 PMCID: PMC7923160 DOI: 10.3390/nu13020659] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 02/10/2021] [Accepted: 02/13/2021] [Indexed: 02/07/2023] Open
Abstract
Background: There are limited data on outcomes of older patients with chronic diseases. Skeletal muscle loss of aging (primary sarcopenia) has been extensively studied but the impact of secondary sarcopenia of chronic disease is not as well evaluated. Older patients with chronic diseases have both primary and secondary sarcopenia that we term compound sarcopenia. We evaluated the clinical impact of compound sarcopenia in hospitalized patients with cirrhosis given the increasing number of patients and high prevalence of sarcopenia in these patients. Design: The Nationwide Inpatients Sample (NIS) database (years 2010–2014) was analyzed to study older patients with cirrhosis. Since there is no universal hospital diagnosis code for “muscle loss”, we used a comprehensive array of codes for “muscle loss phenotype” in the international classification of diseases-9 (ICD-9). A randomly selected 2% sample of hospitalized general medical population (GMP) and inpatients with cirrhosis were stratified into 3 age groups based on age-related changes in muscle mass. In-hospital mortality, length of stay (LoS), cost of hospitalization (CoH), comorbidities and discharge disposition were analyzed. Results. Of 517,605 hospitalizations for GMP and 106,835 hospitalizations for treatment of cirrhosis or a cirrhosis-related complication, 207,266 (40.4%) GMP and 29,018 (27.7%) patients with cirrhosis were >65 years old, respectively. Muscle loss phenotype in both GMP and inpatients with cirrhosis 51–65 years old and >65 years old was significantly (p < 0.001 for all) associated with higher mortality, LoS, and CoH compared to those ≤50 years old. Patients >65 years old with cirrhosis and muscle loss phenotype had higher mortality (adjusted OR: 1.06, 95% CI [1.04, 1.08] and CoH (adjusted odds ratio (OR): 1.10, 95% confidence interval (CI) [1.04, 1.08])) when compared to >65 years old GMP with muscle loss phenotype. Muscle loss in younger patients with cirrhosis (≤50 years old) was associated with worse outcomes compared to GMP >65 years old. Non-home discharges (nursing, skilled, long-term care) were more frequent with increasing age to a greater extent in patients with cirrhosis with muscle loss phenotype for each age stratum. Conclusion: Muscle loss is more frequent in older patients with cirrhosis than younger patients with cirrhosis and older GMP. Younger patients with cirrhosis had clinical outcomes similar to those of older GMP, suggesting an accelerated senescence in cirrhosis. Compound sarcopenia in older patients with cirrhosis is associated with higher inpatient mortality, increased LoS, and CoH compared to GMP with sarcopenia.
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Affiliation(s)
- Nicole Welch
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH 44195, USA;
- Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH 44195, USA; (A.B.); (H.A.); (A.V.)
| | - Amy Attaway
- Department of Pulmonary Medicine, Cleveland Clinic, Cleveland, OH 44195, USA;
| | - Annette Bellar
- Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH 44195, USA; (A.B.); (H.A.); (A.V.)
| | - Hayder Alkhafaji
- Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH 44195, USA; (A.B.); (H.A.); (A.V.)
| | - Adil Vural
- Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH 44195, USA; (A.B.); (H.A.); (A.V.)
| | - Srinivasan Dasarathy
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH 44195, USA;
- Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH 44195, USA; (A.B.); (H.A.); (A.V.)
- Correspondence:
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18
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Assessment of Steatosis and Fibrosis in Liver Transplant Recipients Using Controlled Attenuation Parameter and Liver Stiffness Measurements. Can J Gastroenterol Hepatol 2021; 2021:6657047. [PMID: 33628759 PMCID: PMC7889377 DOI: 10.1155/2021/6657047] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Accepted: 01/15/2021] [Indexed: 12/15/2022] Open
Abstract
AIM The primary objective of this study was to evaluate the prevalence of increased controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) as surrogate markers of liver steatosis and fibrosis in liver transplant recipient (LTR). Secondary objectives were to determine the predictors of increased CAP and LSM in population of LTR. METHODS In this prospective, cross-sectional study, we have evaluated 175 LTRs' mean age as 61 (53-65) with a functioning graft for more than one year who came for regular outpatient examinations to the Department of Gastroenterology, University Hospital (UH) Merkur, Zagreb, Croatia. RESULTS Of 175 analyzed LTRs, 34.28% had obesity, 64.00% had hypertension, 38.28% had diabetes, and 58.85% had hyperlipidemia. The prevalence of liver steatosis was 68.57%, while the prevalence of severe liver steatosis was 46.85%. On multivariate analysis, independent factors associated with liver steatosis were male gender, total cholesterol as positive predictor, and HDL as negative predictor, and independent factors positively associated with severe liver steatosis were higher body mass index (BMI) and higher triglyceride levels. The prevalence of moderate liver fibrosis was 54.85%, while the prevalence of advanced liver fibrosis was 24%. On multivariate analysis, independent factors positively associated with moderate fibrosis were gamma-glutamyl transferase (GGT) and CAP, while the independent factor positively associated with advanced fibrosis was GGT. CONCLUSION Our study showed high prevalence of increased CAP and LSM measurements as surrogate markers of liver steatosis and fibrosis. Metabolic syndrome components were highly present and were associated with CAP and LSM values as well as in the pretransplant setting. Due to high prevalence of metabolic comorbidities and nonalcoholic fatty liver disease in LTRs and the lack of the abnormal liver test in a significant number of these patients, TE with CAP may be a reasonable initial assessment for LTRs with one or more components of the metabolic syndrome.
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19
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Abstract
Cardiovascular disease complications are the leading cause of early (short-term) mortality among liver transplant recipients. The increasingly older candidate pool has multiple comorbidities necessitating cardiac and pulmonary vascular disease risk stratification of patients for optimal allocation of scarce donor livers. Arrhythmias, heart failure, stroke, and coronary artery disease are common pretransplant cardiovascular comorbidities and contribute to cardiovascular complications after liver transplant. Valvular heart disease and portopulmonary hypertension present intraoperative challenges during liver transplant surgery. The Cardiovascular Risk in Orthotopic Liver Transplantation score estimates the risk of cardiovascular complications in liver transplant candidates within the first year after transplant.
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20
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Spiritos Z, Abdelmalek MF. Metabolic syndrome following liver transplantation in nonalcoholic steatohepatitis. Transl Gastroenterol Hepatol 2021; 6:13. [PMID: 33409407 DOI: 10.21037/tgh.2020.02.07] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Accepted: 10/16/2019] [Indexed: 12/13/2022] Open
Abstract
Metabolic syndrome is a major clinical disorder involving metabolic dysregulation characterized clinically with features of central obesity, insulin resistance (IR), type 2 diabetes, hypertension, and dyslipidemia. Metabolic syndrome is strongly associated with the rising prevalence nonalcoholic steatohepatitis, a leading indication for orthotopic liver transplantation in the Western world. The presence or recurrence of metabolic syndrome following liver transplantation can contribute to the development and recurrence of nonalcoholic fatty liver disease (NAFLD) in the liver allograft. In this review, we discuss the endogenous and exogenous drivers of post-transplant metabolic syndrome, role of chronic immunosuppression, and the prevalence and clinical significant of post-transplant metabolic syndrome on nonalcoholic steatohepatitis.
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Affiliation(s)
- Zachary Spiritos
- Division of Gastroenterology and Hepatology, Duke University, Durham, NC, USA
| | - Manal F Abdelmalek
- Division of Gastroenterology and Hepatology, Duke University, Durham, NC, USA
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21
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Willuweit K, Frey A, Hörster A, Saner F, Herzer K. Real-World Administration of Once-Daily MeltDose ® Prolonged-Release Tacrolimus (LCPT) Allows for Dose Reduction of Tacrolimus and Stabilizes Graft Function Following Liver Transplantation. J Clin Med 2020; 10:jcm10010124. [PMID: 33396492 PMCID: PMC7795274 DOI: 10.3390/jcm10010124] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 12/28/2020] [Accepted: 12/28/2020] [Indexed: 01/16/2023] Open
Abstract
The calcineurin inhibitor tacrolimus is included in most immunosuppressive protocols after liver transplantation. This retrospective, observational 24-month study investigated the tolerability of once-daily MeltDose® prolonged-release tacrolimus (LCPT) after switching from twice-daily immediate-release tacrolimus (IR-Tac) in a real-world cohort of 150 patients with previous liver transplantation. No graft rejection or new safety signals were observed. Only 7.3% of patients discontinued LCPT due to side effects. In the overall patient population, median liver transaminases, total cholesterol, triglycerides, glucose, and HbA1c remained constant after switching to LCPT. Total cholesterol significantly decreased (p ≤ 0.002) in patients with initially elevated levels (>200 mg/dL). A total of 71.8% of 96 patients maintained a glomerular filtration rate > 60 mL/min/1.73 m2 throughout the study, while 44.7% of patients were classified as fast metabolizers and 55.3% as slow metabolizers. Median daily tacrolimus dose could be reduced by 50% in fast metabolizers and by 30% in slow metabolizers, while trough levels were maintained in the target range (4–6 ng/mL). In conclusion, our observational study confirmed previous evidence of good overall tolerability and a favorable outcome for the patients after switching from IR-Tac to LCPT after liver transplantation.
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Affiliation(s)
- Katharina Willuweit
- Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany; (A.F.); (A.H.)
- Correspondence: (K.W.); (K.H.); Tel.: +49-2641-860 (K.H.)
| | - Alexandra Frey
- Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany; (A.F.); (A.H.)
| | - Anne Hörster
- Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany; (A.F.); (A.H.)
| | - Fuat Saner
- Department of General, Visceral and Transplant Surgery, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany;
| | - Kerstin Herzer
- Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany; (A.F.); (A.H.)
- Knappschaftsklinik Bad Neuenahr, Georg-Kreuzberg-Straße 2-6, 53474 Bad Neuenahr, Germany
- Correspondence: (K.W.); (K.H.); Tel.: +49-2641-860 (K.H.)
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22
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Sharma P, Arora A. Approach to prevention of non-alcoholic fatty liver disease after liver transplantation. Transl Gastroenterol Hepatol 2020; 5:51. [PMID: 33073046 DOI: 10.21037/tgh.2020.03.02] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2019] [Accepted: 10/15/2019] [Indexed: 12/22/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of liver disease and non-alcoholic steatohepatitis (NASH) related cirrhosis is third common indication for liver transplantation (LT). Patients who have NASH related cirrhosis and are candidates for LT often have multiple comorbidities. These comorbidities need to be addressed before and after transplantation as it affects overall survival. Like hepatitis B, hepatitis C, primary biliary cirrhosis, autoimmune hepatitis which recurs after transplantation, NASH also recurs after transplant however the impact of the recurrence on allograft and patient outcomes is unclear. Limited data suggests that it does not affect graft and patient survival. De novo NAFLD which is defined as occurrence of fatty liver in a patient who did not have fatty liver prior to LT can also occur in the allograft of patients transplanted for non-NAFLD liver disease. Obesity, hyperlipidemia, diabetes as well as steroid dose and duration after LT are common predictors of recurrence of NAFLD after transplantation. Studies on prevention and treatment of NASH in post-transplant patients are lacking. Prevention of weight gain, regular exercises, weight reducing surgery, limited steroid use or steroid free regimen have been tried with varying success. Future studies for the prevention of NAFLD/NASH are required especially in post liver transplant patient.
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Affiliation(s)
- Praveen Sharma
- Department of Gastroenterology & Hepatology, Sir Ganga Ram Hospital, New Delhi, India
| | - Anil Arora
- Department of Gastroenterology & Hepatology, Sir Ganga Ram Hospital, New Delhi, India
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23
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Tanaka S, Fujita K, Makimoto K, Kanaoka M, Yakushiji K, Tanaka R, Harada N, Yoshizumi T. Relationships of accelerometer-determined physical activity with obesity, hypertension, diabetes, dyslipidemia, and health-related quality of life in patients after liver transplantation. Clin Transplant 2020; 34:e14117. [PMID: 33053602 DOI: 10.1111/ctr.14117] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 09/22/2020] [Accepted: 09/30/2020] [Indexed: 11/28/2022]
Abstract
The contribution of physical activity (PA) to the prevention of metabolic abnormalities following liver transplantation (LT) has not been well documented. We aimed to assess PA in post-LT patients and to quantify its relationships with the development of postoperative metabolic abnormalities and health-related quality of life (HRQOL). We recruited 111 patients who had undergone LT ≥ 6 months previously. PA was measured by accelerometry, and HRQOL was evaluated using SF-8. PA was quantified as the number of steps per day, and the time spent performing moderate-to-vigorous PA and light PA per week. The prevalence of hypertension, diabetes, and dyslipidemia increased more than twofold following LT. The proportion of the participants with a sedentary lifestyle (<5000 steps/day) was 36%. Logistic regression analysis showed that postoperative hypertension and obesity were associated with preoperative body mass index and the number of steps taken (in 2000 steps/day increments). Preoperative diabetes was associated with obesity, and PA was associated with physical function-related HRQOL scores. Thus, increasing the number of steps taken per day has the potential to reduce hypertension and obesity, and PA could improve physical function-related HRQOL in patients following LT.
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Affiliation(s)
- Satomi Tanaka
- Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kimie Fujita
- Division of Health Sciences, Graduate School of Medicine, Kyushu University, Fukuoka, Japan
| | - Kiyoko Makimoto
- Department of Nursing, School of Nursing and Rehabilitation, Konan Women's University, Kobe, Japan
| | - Maki Kanaoka
- School of Nursing Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Kanako Yakushiji
- Division of Health Sciences, Graduate School of Medicine, Kyushu University, Fukuoka, Japan
| | - Rumi Tanaka
- Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Noboru Harada
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Chung W, Promrat K, Wands J. Clinical implications, diagnosis, and management of diabetes in patients with chronic liver diseases. World J Hepatol 2020; 12:533-557. [PMID: 33033564 PMCID: PMC7522556 DOI: 10.4254/wjh.v12.i9.533] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 08/03/2020] [Accepted: 08/15/2020] [Indexed: 02/06/2023] Open
Abstract
Diabetes mellitus (DM) negatively affects the development and progression of chronic liver diseases (CLD) of various etiologies. Concurrent DM and CLD are also associated with worse clinical outcomes with respect to mortality, the occurrence of hepatic decompensation, and the development of hepatocellular carcinoma (HCC). Unfortunately, early diagnosis and optimal treatment of DM can be challenging, due to the lack of established clinical guidelines as well as the medical complexity of this patient population. We conducted an exploratory review of relevant literature to provide an up-to-date review for internists and hepatologists caring for this patient population. We reviewed the epidemiological and pathophysiological associations between DM and CLD, the impact of insulin resistance on the progression and manifestations of CLD, the pathogenesis of hepatogenic diabetes, as well as the practical challenges in diagnosis and monitoring of DM in this patient population. We also reviewed the latest clinical evidence on various pharmacological antihyperglycemic therapies with an emphasis on liver disease-related clinical outcomes. Finally, we proposed an algorithm for managing DM in patients with CLD and discussed the clinical and research questions that remain to be addressed.
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Affiliation(s)
- Waihong Chung
- Division of Gastroenterology, Department of Medicine, Rhode Island Hospital, Providence, RI 02905, United States.
| | - Kittichai Promrat
- Division of Gastroenterology and Hepatology, Providence VA Medical Center, Providence, RI 02908, United States
| | - Jack Wands
- Liver Research Center, The Warren Alpert Medical School of Brown University, Providence, RI 02903, United States
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25
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Diwan TS, Lee TC, Nagai S, Benedetti E, Posselt A, Bumgardner G, Noria S, Whitson BA, Ratner L, Mason D, Friedman J, Woodside KJ, Heimbach J. Obesity, transplantation, and bariatric surgery: An evolving solution for a growing epidemic. Am J Transplant 2020; 20:2143-2155. [PMID: 31965711 DOI: 10.1111/ajt.15784] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Revised: 01/05/2020] [Accepted: 01/08/2020] [Indexed: 01/25/2023]
Abstract
The increasing obesity epidemic has major implications in the realm of transplantation. Patients with obesity face barriers in access to transplant and unique challenges in perioperative and postoperative outcomes. Because of comorbidities associated with obesity, along with the underlying end-stage organ disease leading to transplant candidacy, these patients may not even be referred for transplant evaluation, much less be waitlisted or actually undergo transplant. However, the use of bariatric surgery in this population can help optimize the transplant candidacy of patients with obesity and end-stage organ disease and improve perioperative and postoperative outcomes. We review the impact of obesity on kidney, liver, and cardiothoracic transplant candidates and recipients and explore potential interventions to address obesity in these populations.
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Affiliation(s)
| | | | | | | | - Andrew Posselt
- University of California at San Francisco, San Francisco, California, USA
| | | | | | | | - Lloyd Ratner
- Columbia University Medical Center, New York, New York, USA
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26
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Eshraghian A, Nikeghbalian S, Kazemi K, Shamsaeefar A, Geramizadeh B, Malek-Hosseini SA. Non-alcoholic fatty liver disease after liver transplantation in patients with non-alcoholic steatohepatitis and cryptogenic cirrhosis: the impact of pre-transplant graft steatosis. HPB (Oxford) 2020; 22:521-528. [PMID: 31431413 DOI: 10.1016/j.hpb.2019.07.015] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Accepted: 07/27/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) may occur in liver transplant recipients. This study aimed to investigate the prevalence and risk factors of NAFLD after liver transplantation in patients with NASH and cryptogenic cirrhosis, focusing on the impact of graft steatosis. METHODS Patients with NASH and cryptogenic cirrhosis who had undergone liver transplantation in Shiraz transplant center between March 2010 and March 2017 were included. NAFLD was diagnosed after liver transplantation using ultrasonography and transient elastography. RESULTS 73 patients with NASH and 389 with cryptogenic cirrhosis were included. NAFLD was diagnosed in 33 patients (56.9%) in NASH group and 96 patients (26.7%) in cryptogenic group (OR: 3.61; CI: 2.04-6.39; P-Value < 0.001), using ultrasound. Obesity and post-transplant hyperlipidemia were independent predictors of NAFLD after liver transplantation (P < 0.05). NAFLD was diagnosed in 32.9% of patients with graft macrosteatosis compared to 29.9% in patients without graft macrosteatosis (OR: 1.51; 95%CI: 0.755-1.753). 28% of the patients with macrosteatosis ≥30% had NAFLD after liver transplantation compared to 31.4% with macrosteatosis <30% (OR: 1.175; 95% CI: 0.346-2.091). CONCLUSION Liver graft steatosis before transplantation was not associated with the occurrence of NAFLD after liver transplantation.
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Affiliation(s)
- Ahad Eshraghian
- Avicenna Center for Medicine and Organ Transplant, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Saman Nikeghbalian
- Avicenna Center for Medicine and Organ Transplant, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Kourosh Kazemi
- Avicenna Center for Medicine and Organ Transplant, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Alireza Shamsaeefar
- Avicenna Center for Medicine and Organ Transplant, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Bita Geramizadeh
- Avicenna Center for Medicine and Organ Transplant, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Seyed Ali Malek-Hosseini
- Avicenna Center for Medicine and Organ Transplant, Shiraz University of Medical Sciences, Shiraz, Iran
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Oommen T, Arun CS, Kumar H, Nair V, Jayakumar RV, Sudhindran S, Praveen VP, Nithya Abraham NB, Menon U. Incidence of New-Onset Diabetes and PostTransplant Metabolic Syndrome after Liver Transplantation - A Prospective Study from South India. Indian J Endocrinol Metab 2020; 24:165-169. [PMID: 32699784 PMCID: PMC7333767 DOI: 10.4103/ijem.ijem_602_19] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Revised: 12/09/2019] [Accepted: 02/18/2020] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND AND AIMS Liver transplantation has become an effective therapy for patients with end-stage liver disease. The risk of new-onset diabetes after transplantation (NODAT) and posttransplant metabolic syndrome (PTMS) is high among patients after liver transplantation. These are thought to be associated with increased risks of graft rejection, infection, cardiovascular disease, and death. Our study aimed to document the incidence of NODAT and PTMS and analyze pre and posttransplant predictive factors for their development in patients undergoing a liver transplant. METHODS This was a prospective comparative study on 51 patients who underwent live donor liver transplantation. They were evaluated at baseline, 3 and 6 months after transplantation with fasting glucose, lipids, serum insulin levels, C-peptide, and HbA1C. They were followed up at 5 years to document any cardiovascular events or rejection. RESULTS The incidence of preoperative diabetes mellitus (DM) in the study group was 25/51 (49%). The incidence of NODAT was 38.5% (10/26 patients) and PTMS 29% (10/35), respectively. Age (47.7 ± 5.4 vs 41.5 ± 12.7 years), HOMA2 - IR (2.3 ± 1.8 vs 2.1 ± 1.6), serum insulin (16.1 ± 12.0 vs 17.9 ± 14.5), and C-peptide (4.6 ± 0.5 vs 4.8 ± 0.7) were similar at baseline in the NODAT group compared to those who did not develop it. Mean tacrolimus levels were higher in PTMS group (6.8 ± 2.9 vs 5.0. ± 2.0 P value = 0.042). By the end of 5 years, 7 patients expired; 6 due to rejection and one due to cardiovascular disease. Moreover, 2 of these patients had preexisting DM and 2 had NODAT. CONCLUSIONS None of the baseline metabolic factors in patients undergoing liver transplant were predictive of the development of NODAT or PTMS. Mean tacrolimus levels were significantly higher in the PTMS group. A 5-year follow-up showed no excess risk of cardiovascular events or rejection in those with preexisting DM or in those who developed NODAT.
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Affiliation(s)
- Tittu Oommen
- Department of Endocrinology, Amrita Institute of Medical Sciences, Kochi, Kerala, India
| | - Chankramath S. Arun
- Department of Endocrinology, Amrita Institute of Medical Sciences, Kochi, Kerala, India
| | - Harish Kumar
- Department of Endocrinology, Amrita Institute of Medical Sciences, Kochi, Kerala, India
| | - Vasantha Nair
- Department of Endocrinology, Amrita Institute of Medical Sciences, Kochi, Kerala, India
| | - R. V. Jayakumar
- Consultant Endocrinologist, Aster Medcity, Kochi, Kerala, India
| | - S. Sudhindran
- Department of Gastro-Intestinal Surgery, Amrita Institute of Medical Sciences, Kochi, Kerala, India
| | - V. P. Praveen
- Department of Endocrinology, Amrita Institute of Medical Sciences, Kochi, Kerala, India
| | | | - Usha Menon
- Department of Endocrinology, Amrita Institute of Medical Sciences, Kochi, Kerala, India
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Plotogea O, Ilie M, Sandru V, Chiotoroiu A, Bratu O, Diaconu C. Cardiovascular and Metabolic Consequences of Liver Transplantation: A Review. MEDICINA (KAUNAS, LITHUANIA) 2019; 55:489. [PMID: 31443295 PMCID: PMC6722584 DOI: 10.3390/medicina55080489] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/19/2019] [Revised: 08/03/2019] [Accepted: 08/09/2019] [Indexed: 12/14/2022]
Abstract
Liver transplantation (LT) is considered the curative treatment option for selected patients who suffer from end-stage or acute liver disease or hepatic malignancy (primary). After LT, patients should be carefully monitored for complications that may appear, partially due to immunosuppressive therapy, but not entirely. Cardiovascular diseases are frequently encountered in patients with LT, being responsible for high morbidity and mortality. Patients with underlying cardiovascular and metabolic pathologies are prone to complications after the transplant, but these complications can also appear de novo, mostly associated with immunosuppressants. Metabolic syndrome, defined by obesity, hypertension, dyslipidemia, and hyperglycemia, is diagnosed among LT recipients and is aggravated after LT, influencing the long-term survival. In this review, our purpose was to summarize the current knowledge regarding cardiovascular (CV) diseases and the metabolic syndrome associated with LT and to assess their impact on short and long-term morbidity and mortality.
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Affiliation(s)
- Oana Plotogea
- Faculty of Medicine, University of Medicine and Pharmacy "Carol Davila", 050474 Bucharest, Romania
- Gastroenterology Clinic, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania
| | - Madalina Ilie
- Faculty of Medicine, University of Medicine and Pharmacy "Carol Davila", 050474 Bucharest, Romania
- Gastroenterology Clinic, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania
| | - Vasile Sandru
- Gastroenterology Clinic, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania
| | - Alexandru Chiotoroiu
- Surgery Clinic, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania
| | - Ovidiu Bratu
- Faculty of Medicine, University of Medicine and Pharmacy "Carol Davila", 050474 Bucharest, Romania
- Urology Clinic, Emergency University Central Military Hospital, 010242 Bucharest, Romania
| | - Camelia Diaconu
- Faculty of Medicine, University of Medicine and Pharmacy "Carol Davila", 050474 Bucharest, Romania.
- Internal Medicine Clinic, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania.
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Hickman IJ, Coran D, Wallen MP, Kelly J, Barnett A, Gallegos D, Jarrett M, McCoy SM, Campbell KL, Macdonald GA. ‘Back to Life’—Using knowledge exchange processes to enhance lifestyle interventions for liver transplant recipients: A qualitative study. Nutr Diet 2019; 76:399-406. [DOI: 10.1111/1747-0080.12548] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2018] [Revised: 03/07/2019] [Accepted: 04/07/2019] [Indexed: 01/14/2023]
Affiliation(s)
- Ingrid J. Hickman
- Department of Nutrition and DieteticsPrincess Alexandra Hospital Brisbane Queensland Australia
- Mater Research InstituteUniversity of Queensland Brisbane Queensland Australia
- Faculty of MedicineUniversity of Queensland Brisbane Queensland Australia
| | - Donna Coran
- School of Exercise and Nutrition SciencesQueensland University of Technology Brisbane Queensland Australia
| | - Matthew P. Wallen
- School of Human Movement and Nutrition SciencesUniversity of Queensland Brisbane Queensland Australia
| | - Jaimon Kelly
- Faculty of Health Sciences and MedicineBond University Gold Coast Queensland Australia
| | - Amandine Barnett
- Faculty of Health Sciences and MedicineBond University Gold Coast Queensland Australia
| | - Danielle Gallegos
- School of Exercise and Nutrition SciencesQueensland University of Technology Brisbane Queensland Australia
| | - Maree Jarrett
- Queensland Liver Transplant ServicePrincess Alexandra Hospital Brisbane Queensland Australia
| | - Simone M. McCoy
- Department of Nutrition and DieteticsPrincess Alexandra Hospital Brisbane Queensland Australia
| | - Katrina L. Campbell
- Department of Nutrition and DieteticsPrincess Alexandra Hospital Brisbane Queensland Australia
- Faculty of Health Sciences and MedicineBond University Gold Coast Queensland Australia
| | - Graeme A. Macdonald
- Queensland Liver Transplant ServicePrincess Alexandra Hospital Brisbane Queensland Australia
- Faculty of MedicineUniversity of Queensland Brisbane Queensland Australia
- Department of Hepatology and GastroenterologyPrincess Alexandra Hospital Brisbane Queensland Australia
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30
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Choudhary NS, Saigal S. Preventive Strategies for Nonalcoholic Fatty Liver Disease After Liver Transplantation. J Clin Exp Hepatol 2019; 9:619-624. [PMID: 31695252 PMCID: PMC6823688 DOI: 10.1016/j.jceh.2019.05.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Accepted: 05/22/2019] [Indexed: 12/12/2022] Open
Abstract
Post-transplant nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH) is common and can be recurrent or de novo. The available data suggest that progression of fibrosis is accelerated in these patients compared to NASH in general population. The long-term data suggest more risk of metabolic syndrome and associated metabolic comorbidities and cardiovascular disease in these patients. The current review focuses on prevalence and prevention/treatment of post-transplant NAFLD or NASH.
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Affiliation(s)
| | - Sanjiv Saigal
- Address for correspondence: Sanjiv Saigal, Director, Hepatology & Liver Transplant, Medanta Institute of Digestive & Hepatobiliary Sciences &Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurgaon, PIN 122001, India.
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31
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Hu LS, Chai YC, Zheng J, Shi JH, Zhang C, Tian M, Lv Y, Wang B, Jia A. Warm ischemia time and elevated serum uric acid are associated with metabolic syndrome after liver transplantation with donation after cardiac death. World J Gastroenterol 2018; 24:4920-4927. [PMID: 30487701 PMCID: PMC6250918 DOI: 10.3748/wjg.v24.i43.4920] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2018] [Revised: 10/15/2018] [Accepted: 11/08/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To describe the prevalence of posttransplant metabolic syndrome (PTMS) after donation after cardiac death (DCD) liver transplantation (LT) and the pre- and postoperative risk factors.
METHODS One hundred and forty-seven subjects who underwent DCD LT from January 2012 to February 2016 were enrolled in this study. The demographics and the clinical characteristics of pre- and post-transplantation were collected for both recipients and donors. PTMS was defined according to the 2004 Adult Treatment Panel-III criteria. All subjects were followed monthly for the initial 6 mo after discharge, and then, every 3 mo for 2 years. The subjects were followed every 6 mo or as required after 2 years post-LT.
RESULTS The prevalence of PTMS after DCD donor orthotopic LT was 20/147 (13.6%). Recipient’s body mass index (P = 0.024), warm ischemia time (WIT) (P = 0.045), and posttransplant hyperuricemia (P = 0.001) were significantly associated with PTMS. The change in serum uric acid levels in PTMS patients was significantly higher than that in non-PTMS patients (P < 0.001). After the 1st mo, the level of serum uric acid of PTMS patients rose continually over a period, while it was unaltered in non-PTMS patients. After transplantation, the level of serum uric acid in PTMS patients was not associated with renal function.
CONCLUSION PTMS could occur at early stage after DCD LT with growing morbidity with the passage of time. WIT and post-LT hyperuricemia are associated with the prevalence of PTMS. An increased serum uric acid level is highly associated with PTMS and could act as a serum marker in this disease.
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Affiliation(s)
- Liang-Shuo Hu
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Yi-Chao Chai
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Jie Zheng
- Clinical Research Center, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Jian-Hua Shi
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Chun Zhang
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Min Tian
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Yi Lv
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Bo Wang
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Ai Jia
- Department of Gastroenterology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
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Chokesuwattanaskul R, Thongprayoon C, Bathini T, Ungprasert P, Sharma K, Wijarnpreecha K, Pachariyanon P, Cheungpasitporn W. Liver transplantation and atrial fibrillation: A meta-analysis. World J Hepatol 2018; 10:761-771. [PMID: 30386469 PMCID: PMC6206153 DOI: 10.4254/wjh.v10.i10.761] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2018] [Revised: 06/24/2018] [Accepted: 06/28/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To assess prevalence of pre-existing atrial fibrillation (AF) and/or incidence of AF following liver transplantation, and the trends of patient's outcomes overtime; to evaluate impact of pre-existing AF and post-operative AF on patient outcomes following liver transplantation. METHODS A literature search was conducted utilizing MEDLINE, EMBASE and Cochrane Database from inception through March 2018. We included studies that reported: (1) prevalence of pre-existing AF or incidence of AF following liver transplantation; or (2) outcomes of liver transplant recipients with AF. Effect estimates from the individual study were extracted and combined utilizing random-effect, generic inverse variance method of DerSimonian and Laird. The protocol for this meta-analysis is registered with PROSPERO (International Prospective Register of Systematic Reviews, No. CRD42018093644). RESULTS Twelve observational studies with a total of 38586 liver transplant patients were enrolled. Overall, the pooled estimated prevalence of pre-existing AF in patients undergoing liver transplantation was 5.4% (95%CI: 4.9%-5.9%) and pooled estimated incidence of AF following liver transplantation was 8.5% (95%CI: 5.2%-13.6%). Meta-regression analyses were performed and showed no significant correlations between year of study and either prevalence of pre-existing AF (P = 0.08) or post-operative AF after liver transplantation (P = 0.54). The pooled OR of mortality among liver transplant recipients with pre-existing AF was 2.34 (2 studies; 95%CI: 1.10-5.00). In addition, pre-existing AF is associated with postoperative cardiovascular complications among liver transplant recipients (3 studies; OR: 5.15, 95%CI: 2.67-9.92, I 2 = 64%). With limited studies, two studies suggested significant association between new-onset AF and poor clinical outcomes including mortality, cerebrovascular events, post-transplant acute kidney injury, and increased risk of graft failure among liver transplant recipients (P < 0.05). CONCLUSION The overall estimated prevalence of pre-existing AF and incidence of AF following liver transplantation are 5.4% and 8.5%, respectively. Incidence of AF following liver transplant does not seem to decrease overtime. Pre-existing AF and new-onset AF are potentially associated with poor clinical outcomes post liver transplantation.
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Affiliation(s)
- Ronpichai Chokesuwattanaskul
- Division of Cardiovascular Medicine, Department of Internal Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
| | - Charat Thongprayoon
- Department of Internal Medicine, Bassett Medical Center, Cooperstown, NY 13326, United States
| | - Tarun Bathini
- Department of Internal Medicine, Bassett Medical Center, Cooperstown, NY 13326, United States
| | - Patompong Ungprasert
- Clinical Epidemiology Unit, Department of Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Konika Sharma
- Department of Internal Medicine, Bassett Medical Center, Cooperstown, NY 13326, United States
| | - Karn Wijarnpreecha
- Department of Internal Medicine, Bassett Medical Center, Cooperstown, NY 13326, United States
| | - Pavida Pachariyanon
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, United States
| | - Wisit Cheungpasitporn
- Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, United States.
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De-novo nonalcoholic steatohepatitis is associated with long-term increased mortality in liver transplant recipients. Eur J Gastroenterol Hepatol 2018; 30:766-773. [PMID: 29505475 DOI: 10.1097/meg.0000000000001105] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Patients who have undergone transplantation often develop metabolic syndrome (MetS) and de-novo nonalcoholic fatty liver disease (NAFLD). Our aim was to evaluate the impact of metabolic disease on cardiovascular and neoplastic risk and survival. PATIENTS AND METHODS Data from patients who underwent transplantation between 2000 and 2005 in two Italian transplant centers were analyzed. Cox regression analysis was carried out for predictors of de-novo NAFLD and nonalcoholic steatohepatitis (NASH), cardiovascular events, de-novo extrahepatic cancers, and survival. Survival analysis was completed using the Kaplan-Meier method. A P value less than 0.05 was considered significant for all tests. RESULTS De-novo NAFLD was found in one-fifth of 194 patients. Patients with de-novo NAFLD fulfilled the criteria of MetS in 74.4% of cases, while patients without de-novo NAFLD in 29.8% (P=0.000). On multivariate analysis, MetS correlated independently with de-novo NAFLD and this emerged as an independent predictor of cardiovascular events and as a relevant risk factor for solid extrahepatic cancer. Data on smoking habits, which represent a consolidated risk factor for cardiovascular events and cancer in both the general population and patients who have undergone transplantation, are not available. In the subset of histologically proven NASH, it was the strongest predictor of long-term survival (hazard ratio=4.133, 95% confidence interval: 1.385-12.331, P=0.011). CONCLUSION Post-transplant NAFLD represented a strong risk factor for cardiovascular atherosclerotic disease and solid extrahepatic cancer, whereas de novo histologically proven NASH was an independent predictor of long-term mortality.
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34
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Losurdo G, Castellaneta A, Rendina M, Carparelli S, Leandro G, Di Leo A. Systematic review with meta-analysis: de novo non-alcoholic fatty liver disease in liver-transplanted patients. Aliment Pharmacol Ther 2018; 47:704-714. [PMID: 29359341 DOI: 10.1111/apt.14521] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2017] [Revised: 08/26/2017] [Accepted: 12/25/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND De novo non-alcoholic fatty liver disease (NAFLD) in liver-transplanted patients for cirrhosis not due to non-alcoholic steatohepatitis (NASH) is becoming a growing phenomenon. AIMS We performed a systematic review and evaluated the prevalence of this event and possible associated factors. METHODS A literature search in medical databases (PubMed, MEDLINE/OVIDSP, Science Direct and EMBASE) was performed in March 2017. Relevant publications were identified in most important databases. We estimated the pooled prevalence of NAFLD and NASH in patients with liver transplant. The data have been expressed as proportions/percentages, and 95% confidence intervals (CI) were calculated, using the inverse variance method. Odd ratios (OR) and 95% confidence intervals (95% CI) were estimated. RESULTS Twelve studies were selected, enrolling 2166 subjects overall undergoing post-liver transplant biopsy. The pooled weighted prevalence of de novo NAFLD was 26% (95% CI 20%-31%). The pooled weighted prevalence of NASH was 2% (95% CI 0%-3%). The highest prevalences of de novo NAFLD were found for patients transplanted for alcoholic cirrhosis (37%) and cryptogenic cirrhosis (35%) and for patients taking tacrolimus (26%). Tacrolimus showed a risk of NAFLD similar to ciclosporin (OR = 1.02, 95% CI 0.3-3.51). CONCLUSIONS Patients undergoing liver transplant are more prone to experience diabetes, hypertension or dyslipidaemia, and NAFLD may be an important element in this context. In this study, we show how the prevalence of NASH tends to remain significant and similar to the general population. Moreover, this study suggests a possible association with specific transplant indications. Further studies are required to confirm these findings.
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Affiliation(s)
- G Losurdo
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - A Castellaneta
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - M Rendina
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - S Carparelli
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - G Leandro
- Gastroenterology Unit, IRCCS "Saverio De Bellis", Castellana Grotte, BA, Italy
| | - A Di Leo
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
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Abstract
As the cirrhosis progresses, development of complication like ascites, hepatic encephalopathy, variceal bleeding, kidney dysfunction, and hepatocellular carcinoma signify increasing risk of short term mortality. Malnutrition and muscle wasting (sarcopenia) is yet other complications that negatively impact survival, quality of life, and response to stressors, such as infection and surgery in patients with cirrhosis. Conventionally, these are not routinely looked for, because nutritional assessment can be a difficult especially if there is associated fluid retention and/or obesity. Patients with cirrhosis may have a combination of loss of skeletal muscle and gain of adipose tissue, culminating in the condition of "sarcopenic obesity." Sarcopenia in cirrhotic patients has been associated with increased mortality, sepsis complications, hyperammonemia, overt hepatic encephalopathy, and increased length of stay after liver transplantation. Assessment of muscles with cross-sectional imaging studies has become an attractive index of nutritional status evaluation in cirrhosis, as sarcopenia, the major component of malnutrition, is primarily responsible for the adverse clinical consequences seen in patients with liver disease. Cirrhosis is a state of accelerated starvation, with increased gluconeogenesis that requires amino acid diversion from other metabolic functions. Protein homeostasis is disturbed in cirrhosis due to several factors such as hyperammonemia, hormonal, and cytokine abnormalities, physical inactivity and direct effects of ethanol and its metabolites. New approaches to manage sarcopenia are being evolved. Branched chain amino acid supplementation, Myostatin inhibitors, and mitochondrial protective agents are currently in various stages of evaluation in preclinical studies to prevent and reverse sarcopenia, in cirrhosis.
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Key Words
- (PG) SGA, patient-generated SGA
- AMPK, 5′ adenosine monophosphate-activated protein kinase
- ASPEN, American Society of Parenteral and Enteral Nutrition
- ATP, adenosine triphosphate
- Akt/PKB, serine/threonine-specific protein kinase B
- BIA, bio-electric impedance analysis
- BMC, bone mineral content
- BMI, body mass index
- CT, computed tomography
- DDLT, deceased donor liver transplantation
- DRM, disease-related malnutrition
- DXA, dual X-ray absorptiometry
- ESPEN, European Society of Parenteral and Enteral Nutrition
- FFI, Fried Frailty Index
- FFM, fat free mass
- FFMI, fat free mass index
- FM, fat mass
- HE, hepatic encephalopathy
- LDLT, living donor liver transplant
- LST, lean soft tissue
- MAC, mid arm circumference
- MAMC, mid arm muscle circumference
- MELD, model for end-stage liver disease
- MNA, Mini Nutritional Assessment
- MRI, magnetic resonance imaging
- NASH, non-alcoholic steatohepatitis
- PCM, protein-calorie nalnutrition
- REE, resting energy expenditure
- RQ, respiratory quotient (or RQ or respiratory coefficient)
- SGA, Subjective Global Assessment
- SMI, Skeletal Muscle Index
- SPPB, Short Physical Performance Battery
- TIPS, trans jugular intrahepatic portocaval shunts
- TNF, tumour necrosis factor
- TSF, triceps skin fild thickness
- WHO, World Health Organisation
- YPA, total psoas area
- aKG, alfa keto glutarate
- cirrhosis
- mTORC1, mammalian target of rapamycin complex 1
- nutrition
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McCoy SM, Campbell KL, Lassemillante ACM, Wallen MP, Fawcett J, Jarrett M, Macdonald GA, Hickman IJ. Changes in dietary patterns and body composition within 12 months of liver transplantation. Hepatobiliary Surg Nutr 2017; 6:317-326. [PMID: 29152478 DOI: 10.21037/hbsn.2017.01.12] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Background Cardiometabolic risk factors are increasing in liver transplant recipients (LTR). Influencing dietary factors have not been assessed. The aim of this observational study was to assess changes in weight, metabolic function, dietary intake and eating behaviours in the first year after orthotopic liver transplantation (OLT). Methods Consecutive recruitment of 17 patients (14 males) awaiting OLT at a single tertiary hospital. Dietary intake, food behaviours and anthropometry were recorded at baseline, and 6 and 12 months post-transplant. Results By 12 months, patients had gained on average 7.3% of body weight. The prevalence of overweight or obesity increased from baseline 53% to 77% (P=0.001). By 6 months, 65% (n=11/17) of patients had altered glucose metabolism. Dietary intake was consistent with a Western-style dietary pattern with high saturated fat. Over half of the patients (69%, n=11/16) reported low to no depressive feelings and rated their self-esteem as good (53%, n=9/16). The Power of Food Scale increased between pre and post-transplant, indicating a stronger appetitive drive. Conclusions Weight gain occurs early post-transplant, with significant metabolic dysfunction present within 6 months, however is not associated with significant psychological distress. Early dietary intervention designed to limit weight gain and target cardiometabolic health is recommended for this unique patient population.
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Affiliation(s)
- Simone M McCoy
- Department of Nutrition and Dietetics, Princess Alexandra Hospital, Woolloongabba, QLD, Australia
| | - Katrina L Campbell
- Department of Nutrition and Dietetics, Princess Alexandra Hospital, Woolloongabba, QLD, Australia.,Bond Institute of Health and Sport, Faculty of Health Sciences and Medicine, Bond University, Gold Coast, QLD, Australia
| | | | - Matthew P Wallen
- School of Human Movement and Nutrition Sciences, the University of Queensland, St Lucia, QLD, Australia
| | - Jonathan Fawcett
- Queensland Liver Transplant Service, Princess Alexandra Hospital, Woolloongabba, QLD, Australia
| | - Maree Jarrett
- Queensland Liver Transplant Service, Princess Alexandra Hospital, Woolloongabba, QLD, Australia
| | - Graeme A Macdonald
- Department of Hepatology and Gastroenterology, Princess Alexandra Hospital, Woolloongabba, QLD, Australia
| | - Ingrid J Hickman
- Department of Nutrition and Dietetics, Princess Alexandra Hospital, Woolloongabba, QLD, Australia.,Mater Research Institute, University of Queensland, Brisbane, QLD, Australia
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Liu Y, Zhang T, Li C, Ye L, Gu H, Zhong L, Sun H, Sun Y, Peng Z, Fan J. SLC28A3 rs7853758 as a new biomarker of tacrolimus elimination and new-onset hypertension in Chinese liver transplantation patients. Biomark Med 2017. [PMID: 28621555 DOI: 10.2217/bmm-2017-0128] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
AIM The effect of SLC28A3 on tacrolimus disposition and new-onset hypertension (NOHP) after liver transplantation (LT) remains unclear. Methodology & results: A total of 169 patients in two cohorts from the China Liver Transplant Registry database were included. Rs7853758 in recipients'SLC28A3 could predict tacrolimus pharmacokinetics in two sets. The model of donors' CYP3A5 rs776746 and recipients' CYP3A4 rs2242480 could predict tacrolimus metabolism at week 1 and the model of donors' CYP3A5 rs776746, recipients' CYP3A4 rs2242480, recipients' SLC28A3 rs7853758 and hemoglobin could predict tacrolimus disposition at weeks 2, 3 and 4. Besides, recipients' SLC28A3 rs7853758 was a new risk factor of NOHP after LT. CONCLUSION Rs7853758 in recipients' SLC28A3 has a correlation with tacrolimus pharmacokinetics and the risk of NOHP in Chinese LT patients.
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Affiliation(s)
- Yuan Liu
- Department of Hepatobiliary Pancreatic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Tao Zhang
- Department of Hepatobiliary Pancreatic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Changcan Li
- Department of Hepatobiliary Pancreatic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ling Ye
- Department of Hepatobiliary Pancreatic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Haitao Gu
- Department of Hepatobiliary Pancreatic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lin Zhong
- Department of Hepatobiliary Pancreatic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hongcheng Sun
- Department of Hepatobiliary Pancreatic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yahuang Sun
- Department of Hepatobiliary Pancreatic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhihai Peng
- Department of Hepatobiliary Pancreatic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Junwei Fan
- Department of Hepatobiliary Pancreatic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Vafaei F, Dehghani SM, Malekhoseini SA, Karamifar H, Nikeghbalian S. Prevalence of Postoperation Metabolic Syndrome in Pediatric Liver Transplant Patients: A Single Center Experience. EXP CLIN TRANSPLANT 2017; 16:582-587. [PMID: 28540839 DOI: 10.6002/ect.2016.0137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
OBJECTIVES Metabolic syndrome components, such as being overweight or having hypertension, hyperlipidemia, or diabetes mellitus, are common complications after liver transplant in pediatric patients with probable multifactorial causes and increase the risk of cardiovascular complications in adulthood. In this study, our aim was to evaluate the prevalence of these components both before and after transplant surgery. MATERIALS AND METHODS Our study included all children having liver transplant at our institution over a period of 20 years who were under 18 years old and had at least 6 months of posttransplant follow-up. Prevalence of metabolic syndrome components and pretransplant and posttransplant laboratory data of patients were evaluated. RESULTS Over the 20-year study period, 391 liver transplant patients were included in our study, in which 167 were girls (42.7%) and 224 were boys (57.3%). Patients showed a posttransplant hyperlipidemia rate of 7.5%, hyperglycemia rate of 22%, hypertension rate of 9.6%, and metabolic syndrome rate of 50.2%. Pretransplant, the rate of patients with metabolic syndrome was 10.5%. CONCLUSIONS Our study confirmed that the prevalence of metabolic syndrome in patients after liver transplant increases dramatically and should be explored with further research.
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Affiliation(s)
- Farzad Vafaei
- From the Deaprtment of Pediatrics, Shiraz University of Medical Sciences, Shiraz, Iran
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Kappus M, Abdelmalek M. De Novo and Recurrence of Nonalcoholic Steatohepatitis After Liver Transplantation. Clin Liver Dis 2017; 21:321-335. [PMID: 28364816 DOI: 10.1016/j.cld.2016.12.006] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in developing countries. Approximately 25% of patients with NAFLD develop nonalcoholic steatohepatitis (NASH). NASH-related cirrhosis is now a leading listing indication for liver transplantation in the United States. Although posttransplant survival for NASH-related cirrhosis is comparable with that of other liver diseases, many patients have features of metabolic syndrome, which can contribute to a recurrence of NAFLD or NASH. This article reviews the epidemiology, pathophysiology, and treatment of de novo and recurrence of NASH after liver transplantation.
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Affiliation(s)
- Matthew Kappus
- Division of Gastroenterology, Duke University Medical Center, 40 Duke Medicine Circle, PO Box 3913, Durham, NC 27710, USA
| | - Manal Abdelmalek
- Division of Gastroenterology, Duke University Medical Center, 40 Duke Medicine Circle, PO Box 3913, Durham, NC 27710, USA.
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40
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Sourianarayanane A, Arikapudi S, McCullough AJ, Humar A. Nonalcoholic steatohepatitis recurrence and rate of fibrosis progression following liver transplantation. Eur J Gastroenterol Hepatol 2017; 29:481-487. [PMID: 28253211 DOI: 10.1097/meg.0000000000000820] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Nonalcoholic steatohepatitis (NASH) is known to recur following liver transplantation (LT). Metabolic risk factors increase with immunosuppression. However, the rate of fibrosis progression following LT for NASH while on immunosuppression is less clear. AIM The incidences of steatosis, NASH, and fibrosis following LT for NASH were quantified and compared with those transplanted for alcoholic liver disease (ALD). PATIENTS AND METHODS Records of all NASH patients and 1 : 2 match with ALD transplant recipients between 2001 and 2006 were reviewed retrospectively. Patients without liver biopsies beyond 2 months following LT were excluded. RESULTS NASH patients (n=77) were older (P=0.0006) and less likely male (P<0.001) than ALD patients (n=108). The incidence of steatosis, NASH, and fibrosis stage increased at 1, 3, and 5 years in both groups. Although steatosis and nonalcoholic fatty liver disease activity scores were higher, fibrosis was lower in NASH compared with ALD (0.43 vs. 1.0 stage/year; P=0.0045). The incremental increase in the rate of fibrosis was faster in the first year compared with 4-5 years (0.8 vs. 0.04 stage/year) following LT. The rate of fibrosis progression during 4-5 years was decreased in NASH compared with ALD recipients (0.04 vs. 0.33 stage/year; P=0.015). NASH etiology was associated with reduced rate of fibrosis progression (odds ratio=0.67) on multivariate analysis. CONCLUSION Despite having more steatosis and inflammation, progression of fibrosis was slower in NASH compared with ALD recipients. Fibrosis progression slows with time following LT on immunosuppression and approximates the pretransplant progression rate by year 5.
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Affiliation(s)
- Achuthan Sourianarayanane
- Departments of aGastroenterology, Hepatology and NutritionbTransplant Surgery, University of Pittsburgh, Pittsburgh, PennsylvaniacDepartment of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, WisconsindDepartment of Gastroenterology & Hepatology, Cleveland Clinic, Cleveland, Ohio, USA
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Alkhouri N, Hanouneh IA, Zein NN, Lopez R, Kelly D, Eghtesad B, Fung JJ. Liver transplantation for nonalcoholic steatohepatitis in young patients. Transpl Int 2017; 29:418-24. [PMID: 26402655 DOI: 10.1111/tri.12694] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2015] [Revised: 06/29/2015] [Accepted: 09/18/2015] [Indexed: 01/01/2023]
Abstract
Nonalcoholic steatohepatitis (NASH) is the hepatic manifestation of obesity and insulin resistance. The aim of this study was to determine the frequency of NASH as an indication for liver transplantation (LT) in children and young adults and to characterize patient and graft survival. The study included all children and young adult patients (up to the age of 40 years) who underwent LT in the United States for NASH cirrhosis from the 1987 to 2012 United Network for Organ Sharing (UNOS) database. Kaplan-Meier analysis was used to assess patient and graft survival. A total of 330 patients were included, 68% were Caucasian, and the mean BMI was 33.6 ± 6.3. Age at time of LT ranged between 4 and 40 years (mean 33.9 ± 6.6 years). Fourteen subjects were <18 years of age at time of LT and 20 were between the ages of 18 and 25 years. Median follow-up after 1st LT was 45.8 months [10.7, 97.3]. During this time, 30% of subjects (n = 100) died and 11.5% (n = 38) were retransplanted including 13 for NASH recurrence. In conclusion, NASH can progress to end-stage liver disease requiring LT in childhood and early adulthood. A significant number of young patients transplanted for NASH cirrhosis required retransplantation.
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Affiliation(s)
- Naim Alkhouri
- Department of Gastroenterology and Hepatology and Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Ibrahim A Hanouneh
- Department of Gastroenterology and Hepatology and Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Nizar N Zein
- Department of Gastroenterology and Hepatology and Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Rocio Lopez
- Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA
| | - Dympna Kelly
- Department of Gastroenterology and Hepatology and Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Bijan Eghtesad
- Department of Gastroenterology and Hepatology and Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA
| | - John J Fung
- Department of Gastroenterology and Hepatology and Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA
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Lipid profiles of donors and recipients of liver transplant: like father like son. Hepatol Int 2017; 11:300-305. [PMID: 28176203 DOI: 10.1007/s12072-017-9786-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2016] [Accepted: 01/17/2017] [Indexed: 12/19/2022]
Abstract
BACKGROUND/PURPOSE Dyslipidemia is common in liver transplant recipients. This retrospective study investigates whether donors play a role. METHODS Prospectively collected data of donors and recipients of deceased-donor liver transplantation (DDLT) and living-donor liver transplantation (LDLT) were reviewed. Total cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein (HDL) and fasting glucose were compared between groups. HDL ≥1.6 mmol/L at 2 years after transplant was considered the marker of a favorable post-transplant lipid profile in recipients. Univariate and multivariate analyses were performed to identify predictive factors for this marker. RESULTS There were 85 DDLTs and 80 LDLTs. LDLT donors were younger (30 vs. 50 years, p < 0.001) and lighter (58.2 vs. 63.4 kg, p = 0.008) and had a lower body mass index (21.2 vs. 23.7, p < 0.001). The DDLT group had more fatty grafts (p = 0.001) and longer cold (375 vs. 103.5 min, p < 0.001) and warm (50.5 vs. 46 min, p = 0.034) ischemia. LDLT donors had lower fasting glucose (4.85 vs. 7.21 mmol/L, p < 0.001) and triglyceride (0.87 vs. 1.22 mmol/L, p = 0.016) but higher HDL (1.58 vs. 1.39 mmol/L, p = 0.022). LDLT recipients also had higher HDL at 1 year (1.48 vs. 1.28 mmol/L, p = 0.026) and 2 years (1.43 vs. 1.21 mmol/L, p = 0.008). Fourteen (16.5%) DDLT recipients and 27 (33.8%) LDLT recipients had HDL ≥1.6 mmol/L at 2 years. On multivariate analysis, donor HDL ≥1.6 mmol/L (RR 4.311, 95% CI 1.666-11.158, p = 0.003) and recipient body mass index <24 (RR 2.753, 95% CI 1.064-7.127, p = 0.037) were the two independent predictive factors. CONCLUSION LDLT recipients had better lipid profiles than DDLT recipients. The feature of high HDL level in donors was transferred to recipients.
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Andrews R, Queen T, Alcorn J, McCarthy D. A Remembrance of Procedures Past: Late Hepatic Artery Thrombosis. Dig Dis Sci 2017; 62:340-344. [PMID: 27995403 DOI: 10.1007/s10620-016-4407-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2016] [Accepted: 12/02/2016] [Indexed: 12/09/2022]
Affiliation(s)
- Robert Andrews
- Division of Gastroenterology and Hepatology, Department of Medicine, University of New Mexico School of Medicine, Albuquerque, NM, USA
| | - Thomas Queen
- Division of Gastroenterology and Hepatology, Department of Medicine, University of New Mexico School of Medicine, Albuquerque, NM, USA.
- Division of Gastroenterology and Hepatology, MSC 10-5550, 1 University of New Mexico, Albuquerque, NM, 87131, USA.
| | - Joseph Alcorn
- Division of Gastroenterology and Hepatology, Department of Medicine, University of New Mexico School of Medicine, Albuquerque, NM, USA
| | - Denis McCarthy
- Division of Gastroenterology and Hepatology, Department of Medicine, University of New Mexico School of Medicine, Albuquerque, NM, USA
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Pais R, Barritt AS, Calmus Y, Scatton O, Runge T, Lebray P, Poynard T, Ratziu V, Conti F. NAFLD and liver transplantation: Current burden and expected challenges. J Hepatol 2016; 65:1245-1257. [PMID: 27486010 PMCID: PMC5326676 DOI: 10.1016/j.jhep.2016.07.033] [Citation(s) in RCA: 313] [Impact Index Per Article: 34.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2016] [Revised: 07/17/2016] [Accepted: 07/22/2016] [Indexed: 12/26/2022]
Abstract
Because of global epidemics of obesity and type 2 diabetes, the prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing both in Europe and the United States, becoming one of the most frequent causes of chronic liver disease and predictably, one of the leading causes of liver transplantation both for end-stage liver disease and hepatocellular carcinoma. For most transplant teams around the world this will raise many challenges in terms of pre- and post-transplant management. Here we review the multifaceted impact of NAFLD on liver transplantation and will discuss: (1) NAFLD as a frequent cause of cryptogenic cirrhosis, end-stage chronic liver disease, and hepatocellular carcinoma; (2) prevalence of NAFLD as an indication for liver transplantation both in Europe and the United States; (3) the impact of NAFLD on the donor pool; (4) the access of NAFLD patients to liver transplantation and their management on the waiting list in regard to metabolic, renal and vascular comorbidities; (5) the prevalence and consequences of post-transplant metabolic syndrome, recurrent and de novo NAFLD; (6) the alternative management and therapeutic options to improve the long-term outcomes with particular emphasis on the correction and control of metabolic comorbidities.
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Affiliation(s)
- Raluca Pais
- Service Hépatogastroentérologie, Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpétrière - Université Pierre et Marie Curie, Paris, France; UMR_S 938, INSERM - CDR Saint Antoine, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.
| | - A Sidney Barritt
- Division of Gastroenterology and Hepatology, UNC School of Medicine, University of North Carolina at Chapel Hill, 8004 Burnett Womack, CB #7584, Chapel Hill, NC 27599-7584, USA
| | - Yvon Calmus
- Service Hépatogastroentérologie, Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpétrière - Université Pierre et Marie Curie, Paris, France; UMR_S 938, INSERM - CDR Saint Antoine, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Olivier Scatton
- Service de Chirurgie Hépato-biliaire et Transplantation Hépatique, Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpétrière - Université Pierre et Marie Curie, Paris, France
| | - Thomas Runge
- Division of Gastroenterology and Hepatology, UNC School of Medicine, University of North Carolina at Chapel Hill, 8004 Burnett Womack, CB #7584, Chapel Hill, NC 27599-7584, USA
| | - Pascal Lebray
- Service Hépatogastroentérologie, Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpétrière - Université Pierre et Marie Curie, Paris, France
| | - Thierry Poynard
- Service Hépatogastroentérologie, Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpétrière - Université Pierre et Marie Curie, Paris, France; UMR_S 938, INSERM - CDR Saint Antoine, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Vlad Ratziu
- Service Hépatogastroentérologie, Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpétrière - Université Pierre et Marie Curie, Paris, France; UMR_S 938, INSERM - CDR Saint Antoine, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Filomena Conti
- Service Hépatogastroentérologie, Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpétrière - Université Pierre et Marie Curie, Paris, France; UMR_S 938, INSERM - CDR Saint Antoine, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
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Pisano G, Fracanzani AL, Caccamo L, Donato MF, Fargion S. Cardiovascular risk after orthotopic liver transplantation, a review of the literature and preliminary results of a prospective study. World J Gastroenterol 2016; 22:8869-8882. [PMID: 27833378 PMCID: PMC5083792 DOI: 10.3748/wjg.v22.i40.8869] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Revised: 08/27/2016] [Accepted: 09/28/2016] [Indexed: 02/06/2023] Open
Abstract
Improved surgical techniques and greater efficacy of new anti-rejection drugs have significantly improved the survival of patients undergoing orthotopic liver transplantation (OLT). This has led to an increased incidence of metabolic disorders as well as cardiovascular and cerebrovascular diseases as causes of morbidity and mortality in OLT patients. In the last decade, several studies have examined which predisposing factors lead to increased cardiovascular risk (i.e., age, ethnicity, diabetes, NASH, atrial fibrillation, and some echocardiographic parameters) as well as which factors after OLT (i.e., weight gain, metabolic syndrome, immunosuppressive therapy, and renal failure) are linked to increased cardiovascular mortality. However, currently, there are no available data that evaluate the development of atherosclerotic damage after OLT. The awareness of high cardiovascular risk after OLT has not only lead to the definition of new but generally not accepted screening of high risk patients before transplantation, but also to the need for careful patient follow up and treatment to control metabolic and cardiovascular pathologies after transplant. Prospective studies are needed to better define the predisposing factors for recurrence and de novo occurrence of metabolic alterations responsible for cardiovascular damage after OLT. Moreover, such studies will help to identify the timing of disease progression and damage, which in turn may help to prevent morbidity and mortality for cardiovascular diseases. Our preliminary results show early occurrence of atherosclerotic damage, which is already present a few weeks following OLT, suggesting that specific, patient-tailored therapies should be started immediately post OLT.
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Xue M, Lv C, Chen X, Liang J, Zhao C, Zhang Y, Huang X, Sun Q, Wang T, Gao J, Zhou J, Yu M, Fan J, Gao X. Donor liver steatosis: A risk factor for early new-onset diabetes after liver transplantation. J Diabetes Investig 2016; 8:181-187. [PMID: 27511316 PMCID: PMC5334314 DOI: 10.1111/jdi.12560] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2015] [Revised: 07/26/2016] [Accepted: 08/04/2016] [Indexed: 01/01/2023] Open
Abstract
AIMS/INTRODUCTION To investigate whether donor liver steatosis increases the incidence of new-onset diabetes after transplantation (NODAT) in liver transplant recipients. MATERIALS AND METHODS We retrospectively analyzed liver transplant recipients at Zhongshan Hospital, Shanghai, China, from April 2001 to December 2014. The final analysis involved 763 patients. The cumulative incidence of NODAT at 1, 3, 5 and 10 years after liver transplantation was investigated. Furthermore, according to the findings of donor liver biopsy before transplantation, patients were divided into steatotic and non-steatotic donor liver groups, and NODAT incidence was compared between these groups. Multivariate Cox regression was used to explore the risk factors for NODAT in the patients. RESULTS Of the 763 donors, 309 (40.5%) had liver steatosis. At the end of follow up, 130 (42.1%) patients in the steatotic donor liver group developed NODAT, an incidence that exceeded that in the non-steatotic donor liver group (P = 0.001). The cumulative incidence of NODAT among all patients at 1, 3, 5, and 10 years after transplantation was 33, 43, 50 and 56%, respectively. The cumulative incidences of NODAT at 1, 3, 5 and 10 years in the steatotic donor liver group were significantly higher than those in the non-steatotic donor liver group (P = 0.003). Multivariate Cox regression analyses showed that donor liver steatosis was an independent risk factor for NODAT among liver transplant recipients, after other potential risk factors were adjusted for (hazard ratio 1.774, 95% confidence interval: 1.025-3.073; P = 0.041). CONCLUSIONS Donor liver steatosis increases NODAT incidence among liver transplant recipients.
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Affiliation(s)
- Mengjuan Xue
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Chaoyang Lv
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xianying Chen
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.,Department of Endocrinology and Metabolism, Hainan Provincial Nong Ken Hospital, Hainan, China
| | - Jing Liang
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Chenhe Zhao
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yao Zhang
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xiaowu Huang
- Department of Liver Surgery, Zhongshan Hospital, Fudan University, China
| | - Qiman Sun
- Department of Liver Surgery, Zhongshan Hospital, Fudan University, China
| | - Ting Wang
- Department of Liver Surgery, Zhongshan Hospital, Fudan University, China
| | - Jian Gao
- Center of Clinical Epidemiology and Evidence-based Medicine, Fudan University, Shanghai, China
| | - Jian Zhou
- Department of Liver Surgery, Zhongshan Hospital, Fudan University, China
| | - Mingxiang Yu
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jia Fan
- Department of Liver Surgery, Zhongshan Hospital, Fudan University, China
| | - Xin Gao
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
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Use of Six-Minute Walk Test to Measure Functional Capacity After Liver Transplantation. Phys Ther 2016; 96:1456-67. [PMID: 27055540 PMCID: PMC5009186 DOI: 10.2522/ptj.20150376] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2015] [Accepted: 03/10/2016] [Indexed: 12/17/2022]
Abstract
BACKGROUND Functional impairment is common in people with chronic liver disease (CLD), and improvement is expected following liver transplantation (LT). The Six-Minute Walk Test (6MWT) is an objective measure of functional performance. OBJECTIVE The aims of this study were: (1) to evaluate the feasibility of 6MWT performance after LT, (2) to compare post-LT 6MWT performance over time between patients with and without CLD, (3) to determine when post-LT 6MWT performance approaches expected values, and (4) to investigate predictors of poor 6MWT performance. METHODS The 6MWT was performed by 162 consecutive ambulatory participants (50 healthy controls, 62 with CLD, 50 with LT). Sex, age, and body mass index were used to predict expected 6MWT performance. Chi-square testing, analysis of variance, and Pearson coefficients compared percentage of predicted 6-minute walk distance (%6MWD) across groups. Multivariable mixed models assessed predictors of improvement. RESULTS The participants' mean age was 53.5 years (SD=13.0), 39.5% were female, and 39.1% were nonwhite. At 1-month post-LT, only 52% of all LT recipients met the inclusion criteria for 6MWT performance. Mean %6MWD values for female participants improved from 49.8 (SD=22.2) at 1 month post-LT to 90.6 (SD=12.8) at 1 year post-LT (P<.0001), which did not differ statistically from the CLD group (X̅=95.9, SD=15.6) or the control group (X̅=95.6, SD=18.0) (P=.58). However, at 1-year post-LT, mean %6MWD values for male participants (X̅=80.4, SD=19.5) remained worse than for both the CLD group (X̅=93.3, SD=13.7) and the control group (X̅=91.9, SD=14.3) (P=.03). Six-Minute Walk Test performance was directly correlated with the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) physical component score (r=.51, P<.01) and was inversely correlated with nonalcoholic steatohepatitis (r=-.52, P<.01) and diabetes (r=-.48, P<.05). In multivariate analysis adjusted for age and sex, hepatitis C independently predicted 6MWT improvement (estimated β=69.8, standard error=27.6, P=.01). LIMITATIONS A significant proportion of patients evaluated for enrollment were excluded due to level of illness early after LT (n=99, 47.4%). Thus, sampling bias occurred in this study toward patients without significant postoperative complications. CONCLUSIONS The 6MWT is a simple test of physical functioning but may be difficult to apply in LT recipients. The 6MWT performance improved following LT but was lower than expected, suggesting a low level of fitness up to 1 year following LT.
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Mikolasevic I, Orlic L, Hrstic I, Milic S. Metabolic syndrome and non-alcoholic fatty liver disease after liver or kidney transplantation. Hepatol Res 2016; 46:841-52. [PMID: 26713425 DOI: 10.1111/hepr.12642] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2015] [Revised: 11/05/2015] [Accepted: 12/18/2015] [Indexed: 12/12/2022]
Abstract
Transplantation is a definitive treatment option for patients with end-stage liver disease, and for some patients with acute liver failure, hepatocellular carcinoma or end-stage renal disease. Long-term post-transplantation complications have become an important medical issue, and cardiovascular diseases (CVD) are now the leading cause of mortality in liver or kidney transplant recipients. The increased prevalence of metabolic syndrome (MS) likely plays a role in the high incidence of post-transplantation CVD. MS and its hepatic manifestation, non-alcoholic fatty liver disease (NAFLD), are prevalent among the general population and in pre- and post-transplantation settings. MS components are associated with recurrent or de novo NAFLD in transplant recipients, potentially influencing post-transplantation survival. Moreover, recent data reveal an important association between NAFLD and risk of incident of chronic kidney disease (CKD). Therefore, NAFLD identification could represent an additional clinical feature for improving the stratification of liver and kidney transplant recipients with regards to risks of CVD, CKD and renal allograft dysfunction. All MS components are potentially modifiable; therefore, it is crucial that hepatologists, nephrologists and primary care physicians become more engaged in managing post-transplantation metabolic complications. The present review discusses the recent clinical evidence regarding the importance of MS and its components after liver and kidney transplantation, as well as the link between MS and NAFLD after liver and kidney transplantation.
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Affiliation(s)
| | - Lidija Orlic
- Nephrology, Dialysis and Kidney Transplantation, UHC Rijeka, Rijeka, Croatia
| | - Irena Hrstic
- General Hospital Pula, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Sandra Milic
- Departments of Gastroenterology, UHC Rijeka, Rijeka, Croatia
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Jiménez-Pérez M, González-Grande R, Omonte Guzmán E, Amo Trillo V, Rodrigo López JM. Metabolic complications in liver transplant recipients. World J Gastroenterol 2016; 22:6416-6423. [PMID: 27605877 PMCID: PMC4968123 DOI: 10.3748/wjg.v22.i28.6416] [Citation(s) in RCA: 58] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2016] [Revised: 05/25/2016] [Accepted: 06/13/2016] [Indexed: 02/06/2023] Open
Abstract
The metabolic syndrome (MS), which includes obesity, dyslipidaemia, hypertension and hyperglycaemia according to the most widely accepted definitions now used, is one of the most common post-transplant complications, with a prevalence of 44%-58%. The MS, together with the immunosuppression, is considered the main risk factor for the development of cardiovascular disease (CVD) in transplant recipients, which in turn accounts for 19%-42% of all deaths unrelated to the graft. The presence of MS represents a relative risk for the development of CVD and death of 1.78. On the other hand, non-alcoholic fatty liver disease (NAFLD), considered as the manifestation of the MS in the liver, is now the second leading reason for liver transplantation in the United States after hepatitis C and alcohol. NAFLD has a high rate of recurrence in the liver graft and a direct relation with the worsening of other metabolic disorders, such as insulin resistance or diabetes mellitus. Consequently, it is vitally important to identify and treat as soon as possible such modifiable factors as hypertension, overweight, hyperlipidaemia or diabetes in transplanted patients to thus minimise the impact on patient survival. Additionally, steroid-free regimens are favoured, with minimal immunosuppression to limit the possible effects on the development of the MS.
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Xue M, Lv C, Chen X, Huang X, Sun Q, Wang T, Liang J, Zhang Y, He S, Gao J, Zhou J, Yu M, Fan J, Gao X. Effect of interleukin-2 receptor antagonists on new-onset diabetes after liver transplantation: A retrospective cohort study. J Diabetes 2016; 8:579-87. [PMID: 26588180 DOI: 10.1111/1753-0407.12356] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2015] [Revised: 09/28/2015] [Accepted: 11/10/2015] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND The aim of the present retrospective observational study was to examine the effect of interleukin-2 receptor antagonists (IL-2Ra) on new-onset diabetes after transplantation (NODAT) in liver transplant recipients. METHODS Pre- and postoperative clinical data of 781 patients undergoing liver transplantation between April 2001 and December 2014 at Zhongshan Hospital, Fudan University, were analyzed. Patients were divided into two groups depending on the use of IL-2Ra (IL-2Ra and non-IL-2Ra). The cumulative incidence of NODAT was compared between the IL-2Ra and non-IL-2Ra groups and the effect of IL-2Ra on the incidence of NODAT in liver transplant recipients was evaluated. RESULTS Of the 781 patients in the study, 451 received IL-2Ra. During follow-up, 138 (41.8%) and 137 (30.4%) patients in the non-IL-2Ra and IL-2Ra groups, respectively, developed NODAT (P = 0.001). The cumulative incidence of NODAT at 1, 3, 5, and 8 years after transplantation in the IL-2Ra group was 30%, 38%, 45%, and 54%, respectively; these values were substantially lower than corresponding values for the non-IL-2Ra group (P < 0.05). Cox regression analyses showed that IL-2Ra was a protective factor against NODAT development (odds ratio 0.685; 95% confidence interval 0.473-0.991; P = 0.044). This was independent of age, sex, donor type, hepatitis virus infection, body mass index, history of hypertension, preoperative liver function, preoperative fasting plasma glucose, total cholesterol, and total triglyceride levels, severity of liver cirrhosis, acute rejection, initial immunosuppressant regimen type, and postoperative immunosuppressant levels. CONCLUSION In conclusion, IL-2Ra reduces the risk of NODAT in liver transplant recipients.
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Affiliation(s)
- Mengjuan Xue
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Chaoyang Lv
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Xianying Chen
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
- Department of Endocrinology and Metabolism, Hainan Provincial Nong Ken Hospital, Hainan, China
| | - Xiaowu Huang
- Department of Liver Surgery, Zhongshan Hospital, Shanghai, China
| | - Qiman Sun
- Department of Liver Surgery, Zhongshan Hospital, Shanghai, China
| | - Ting Wang
- Department of Liver Surgery, Zhongshan Hospital, Shanghai, China
| | - Jing Liang
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Yao Zhang
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Shunmei He
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Jian Gao
- Center of Clinical Epidemiology and Evidence-Based Medicine, Fudan University, Shanghai, China
| | - Jian Zhou
- Department of Liver Surgery, Zhongshan Hospital, Shanghai, China
| | - Mingxiang Yu
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Jia Fan
- Department of Liver Surgery, Zhongshan Hospital, Shanghai, China
| | - Xin Gao
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
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