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1
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Mehta A. Managing dyslipidemia in solid organ transplant patients. Indian Heart J 2024; 76 Suppl 1:S93-S95. [PMID: 38199560 PMCID: PMC11019326 DOI: 10.1016/j.ihj.2024.01.004] [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: 10/21/2023] [Revised: 11/28/2023] [Accepted: 01/06/2024] [Indexed: 01/12/2024] Open
Abstract
Solid organ transplant recipients face an increased risk of dyslipidemia, which contributes to cardiovascular complications. Commonly used drugs such as ciclosporin and tacrolimus can aggravate and cause dyslipidemia. Immunosuppressive drugs particularly ciclosporin and tacrolimus are also known to worsen dyslipidemia in transplant recipients. Mammalian target of rapamycin (mTOR) inhibitors like sirolimus and everolimus also alter lipid metabolism. Lifestyle and dietary modifications should be encouraged. Careful consideration of immunosuppressant choices is also vital to control dyslipidemia. Statins are recommended as first-line agents for lipid-lowering therapy, with consideration for potential drug interactions. Other options, such as ezetimibe and nicotinic acid, may be considered as alternatives. The management of dyslipidemia in renal transplant patients mainly involves statin therapy, although the clinical effectiveness in this population is not well-documented. Lifestyle modifications, careful drug selection, and statin therapy are key components in managing dyslipidemia in solid organ transplant patients.
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2
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Gabrielli F, Golfieri L, Nascimbeni F, Andreone P, Gitto S. Metabolic Disorders in Liver Transplant Recipients: The State of the Art. J Clin Med 2024; 13:1014. [PMID: 38398327 PMCID: PMC10889804 DOI: 10.3390/jcm13041014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 02/05/2024] [Accepted: 02/08/2024] [Indexed: 02/25/2024] Open
Abstract
Liver transplantation represents a chief therapeutic approach for acute liver failure, end-stage liver disease and hepatocellular carcinoma. Despite witnessing advancements in short- and medium-term survival over recent decades, attributed to refinements in surgical techniques and immunosuppressive protocols, long-term mortality remains impervious to modification. Notably, cardiovascular disease emerges as a predominant cause of mortality among liver transplant recipients. This trend is accentuated by the increasing prominence of non-alcoholic steatohepatitis-related cirrhosis as an indication for liver transplantation. Moreover, the administration of immunosuppressive agents is intricately linked to the degradation of the metabolic profile in liver transplant recipients, thereby contributing to the initiation or exacerbation of cardiovascular risk factors, such as hypertension, diabetes, and dyslipidaemia. In addition, the post-liver transplantation period is marked by a decline in lifestyle quality and a failure to acknowledge the psychological distress experienced by patients throughout the transplant process. These factors can precipitate a deterioration in the patient's metabolic profile, exacerbated by suboptimal therapeutic compliance. This narrative review aims to comprehensively address the principal metabolic disorders intricately associated with liver transplantation.
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Affiliation(s)
- Filippo Gabrielli
- Internal and Metabolic Medicine, Department of Medical and Surgical Sciences for Children & Adults, AOU di Modena, University of Modena and Reggio Emilia, 41126 Modena, Italy
- Department of Surgical Sciences, University of Bologna, 40126 Bologna, Italy
| | - Lucia Golfieri
- Clinical Psychology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant’Orsola, 40138 Bologna, Italy
| | - Fabio Nascimbeni
- Internal and Metabolic Medicine, Department of Medical and Surgical Sciences for Children & Adults, AOU di Modena, University of Modena and Reggio Emilia, 41126 Modena, Italy
| | - Pietro Andreone
- Internal and Metabolic Medicine, Department of Medical and Surgical Sciences for Children & Adults, AOU di Modena, University of Modena and Reggio Emilia, 41126 Modena, Italy
- Postgraduate School of Allergology and Clinical Immunology, University of Modena and Reggio Emilia, 41126 Modena, Italy
| | - Stefano Gitto
- Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy
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3
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Fuochi E, Anastasio L, Lynch EN, Campani C, Dragoni G, Milani S, Galli A, Innocenti T. Main factors influencing long-term outcomes of liver transplantation in 2022. World J Hepatol 2023; 15:321-352. [PMID: 37034235 PMCID: PMC10075010 DOI: 10.4254/wjh.v15.i3.321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 11/24/2022] [Accepted: 02/22/2023] [Indexed: 04/11/2023] Open
Abstract
Liver transplant (LT) outcomes have markedly improved in the recent decades, even if long-term morbidity and mortality are still considerable. Most of late deaths are independent from graft function and different comorbidities, including complications of metabolic syndrome and de novo neoplasms, seem to play a key role in determining long-term outcomes in LT recipients. This review discusses the main factors associated with late mortality and suggests possible strategies to improve long-term management and follow-up after liver transplantation. In particular, the reduction of drug toxicity, the use of tools to identify high-risk patients, and setting up a multidisciplinary team also for long-term management of LT recipients may further improve survival after liver transplantation.
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Affiliation(s)
- Elisa Fuochi
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Lorenzo Anastasio
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Erica Nicola Lynch
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Claudia Campani
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy
| | - Gabriele Dragoni
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
- Department of Medical Biotechnologies, University of Siena, Siena 53100, Italy
| | - Stefano Milani
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Andrea Galli
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Tommaso Innocenti
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
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Iannuzzo G, Cuomo G, Di Lorenzo A, Tripaldella M, Mallardo V, Iaccarino Idelson P, Sagnelli C, Sica A, Creta M, Baltar J, Crocetto F, Bresciani A, Gentile M, Calogero A, Giallauria F. Dyslipidemia in Transplant Patients: Which Therapy? J Clin Med 2022; 11:4080. [PMID: 35887846 PMCID: PMC9318180 DOI: 10.3390/jcm11144080] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 07/11/2022] [Accepted: 07/11/2022] [Indexed: 12/17/2022] Open
Abstract
Cardiovascular disease is the most important cause of death worldwide in recent years; an increasing trend is also shown in organ transplant patients subjected to immunosuppressive therapies, in which cardiovascular diseases represent one of the most frequent causes of long-term mortality. This is also linked to immunosuppressant-induced dyslipidemia, which occurs in 27 to 71% of organ transplant recipients. The aim of this review is to clarify the pathophysiological mechanisms underlying dyslipidemia in patients treated with immunosuppressants to identify immunosuppressive therapies which do not cause dyslipidemia or therapeutic pathways effective in reducing hypercholesterolemia, hypertriglyceridemia, or both, without further adverse events.
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Affiliation(s)
- Gabriella Iannuzzo
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Via S. Pansini 5, 80131 Naples, Italy; (G.I.); (M.T.); (V.M.); (P.I.I.); (M.G.)
| | - Gianluigi Cuomo
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Via S. Pansini 5, 80131 Naples, Italy; (G.C.); (A.D.L.); (F.G.)
| | - Anna Di Lorenzo
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Via S. Pansini 5, 80131 Naples, Italy; (G.C.); (A.D.L.); (F.G.)
| | - Maria Tripaldella
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Via S. Pansini 5, 80131 Naples, Italy; (G.I.); (M.T.); (V.M.); (P.I.I.); (M.G.)
| | - Vania Mallardo
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Via S. Pansini 5, 80131 Naples, Italy; (G.I.); (M.T.); (V.M.); (P.I.I.); (M.G.)
| | - Paola Iaccarino Idelson
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Via S. Pansini 5, 80131 Naples, Italy; (G.I.); (M.T.); (V.M.); (P.I.I.); (M.G.)
| | - Caterina Sagnelli
- Department of Mental Health and Public Medicine, University of Campania “Luigi Vanvitelli”, Via S. Pansini 5, 80131 Naples, Italy;
| | - Antonello Sica
- Department of Precision Medicine University of Campania “Luigi Vanvitelli”, Naples, Via S. Pansini 5, 80131 Naples, Italy;
| | - Massimiliano Creta
- Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, Naples, Via S. Pansini 5, 80131 Naples, Italy; (M.C.); (F.C.)
| | - Javier Baltar
- Servicio de Cirugía General, Xerencia de Xestión Integrada de Santiago (XXIS/SERGAS), 15706 Santiago de Compostela, Spain;
| | - Felice Crocetto
- Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, Naples, Via S. Pansini 5, 80131 Naples, Italy; (M.C.); (F.C.)
| | - Alessandro Bresciani
- Department of Medicine and Medical Specialties, A. Cardarelli Hospital, 80131 Naples, Italy;
| | - Marco Gentile
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Via S. Pansini 5, 80131 Naples, Italy; (G.I.); (M.T.); (V.M.); (P.I.I.); (M.G.)
| | - Armando Calogero
- Servicio de Cirugía General, Xerencia de Xestión Integrada de Santiago (XXIS/SERGAS), 15706 Santiago de Compostela, Spain;
| | - Francesco Giallauria
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Via S. Pansini 5, 80131 Naples, Italy; (G.C.); (A.D.L.); (F.G.)
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5
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Gitto S, Falcini M, Marra F. Metabolic Disorders After Liver Transplantation. Metab Syndr Relat Disord 2020; 19:65-69. [PMID: 33104408 DOI: 10.1089/met.2020.0068] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Early after surgery, liver transplant (LT) recipients often develop weight gain due to an increase of caloric intake and fat mass (without recovery of muscle frame). This modification of body composition together with a negative metabolic impact of immunosuppressive drugs leads to a high prevalence of all the main metabolic disorders. Indeed, as expected, transplanted patients show a higher cardiovascular risk in comparison with general population. Notably, seeing the increase of mean age of transplanted population, metabolic disorders represent the true challenge for the transplant community. Considering the lack of evidences or clear indications about prevention, early diagnosis and treatment of metabolic disorders after LT, it would be mandatory to develop targeted further studies on this matter.
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Affiliation(s)
- Stefano Gitto
- Internal Medicine and Liver Unit, Department of Experimental and Clinical Medicine, University Hospital Careggi, University of Florence, Florence, Italy
| | - Margherita Falcini
- Internal Medicine and Liver Unit, Department of Experimental and Clinical Medicine, University Hospital Careggi, University of Florence, Florence, Italy
| | - Fabio Marra
- Internal Medicine and Liver Unit, Department of Experimental and Clinical Medicine, University Hospital Careggi, University of Florence, Florence, Italy
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Kim NG, Sharma A, Saab S. Cardiovascular and metabolic disease in the liver transplant recipient. Best Pract Res Clin Gastroenterol 2020; 46-47:101683. [PMID: 33158470 DOI: 10.1016/j.bpg.2020.101683] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Accepted: 08/31/2020] [Indexed: 01/31/2023]
Abstract
Liver transplantation has led to great improvements in long-term survival in patients with decompensated liver disease and hepatocellular carcinoma. Cardiovascular disease is the leading cause of non-graft-related deaths and has increased prevalence in liver allograft recipients. This is partly secondary to higher post-transplant rates of metabolic risk factors-notably obesity, hypertension, dyslipidemia, and diabetes mellitus, which comprise metabolic syndrome. Post-transplantation metabolic syndrome is expected to be a growing factor in morbidity and mortality as transplant candidates trend older, the rates of metabolic risk factors in the general population increase, non-alcoholic steatohepatitis grows disproportionally as an indication for transplantation, and post-transplantation survival lengthens. This review discusses the incidence and contributory factors for post-transplant increases in metabolic disease, as well as the burden of cardiovascular disease in the liver allograft recipient. Patients with pre-transplant diabetes or obesity are at particularly high risk for post-transplant metabolic syndrome, and would likely benefit from closer surveillance and more aggressive medical management of risk factors. In metabolic disease resistant to initial medical therapies, tailoring of immunosuppressive regimens may further assist in minimizing long-term cardiovascular disease, although this must be done with caution to avoid worsening the risk of graft failure.
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Affiliation(s)
- Nathan G Kim
- Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA
| | - Avneesh Sharma
- Virginia Commonwealth University School of Medicine, Richmond, VA, USA
| | - Sammy Saab
- Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA; Department of Surgery, University of California at Los Angeles, Los Angeles, CA, USA.
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Zhang C, Chen K, Wei R, Fan G, Cai X, Xu L, Cen B, Wang J, Xie H, Zheng S, Xu X. The circFASN/miR-33a pathway participates in tacrolimus-induced dysregulation of hepatic triglyceride homeostasis. Signal Transduct Target Ther 2020; 5:23. [PMID: 32296037 PMCID: PMC7099020 DOI: 10.1038/s41392-020-0105-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2019] [Accepted: 12/12/2019] [Indexed: 12/14/2022] Open
Abstract
Dyslipidemia exhibits a high incidence after liver transplantation, in which tacrolimus, a widely used immunosuppressant, plays a fundamental role. MicroRNAs and related circRNAs represent a class of noncoding RNAs that have been recognized as important regulators of genes associated with lipid metabolism. However, their transcriptional activities and functional mechanisms in tacrolimus-related dyslipidemia remain unclear. In this study, we observed that tacrolimus could induce triglyceride accumulation in hepatocytes by stimulating sterol response element-binding proteins (SREBPs) and miR-33a. Our in silico and experimental analyses identified miR-33a as a direct target of circFASN. Tacrolimus could downregulate circFASN and result in elevated miR-33a in vivo and in vitro. Overexpression of circFASN or silencing of miR-33a decreased the promoting effects of tacrolimus on triglyceride accumulation. Clinically, the incidence of dyslipidemia in liver transplant recipients with elevated serum miR-33a after liver transplantation was higher than that in patients without elevated serum miR-33a (46.3% vs. 18.8% p = 0.012, n = 73). Our results showed that the circFASN/miR-33a regulatory system plays a distinct role in tacrolimus-induced disruption of lipid homeostasis. MiR-33a is likely a risk factor for tacrolimus-related dyslipidemia, providing a potential therapeutic target to combat tacrolimus-induced dyslipidemia after liver transplantation.
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Affiliation(s)
- Chenzhi Zhang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, China.,Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, 310000, China
| | - Kangchen Chen
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, China.,Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, 310000, China
| | - Rongli Wei
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, China.,Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, 310000, China
| | - Guanghan Fan
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, China.,Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, 310000, China
| | - Xuechun Cai
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, China.,Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, 310000, China
| | - Li Xu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, China.,Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, 310000, China
| | - Beini Cen
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, 310000, China
| | - Jianguo Wang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, China.,Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, 310000, China
| | - Haiyang Xie
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, 310000, China
| | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, China. .,Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, 310000, China. .,Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital, Hangzhou, 310000, China.
| | - Xiao Xu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, China. .,Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, 310000, China.
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8
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Germani G, Laryea M, Rubbia-Brandt L, Egawa H, Burra P, OʼGrady J, Watt KD. Management of Recurrent and De Novo NAFLD/NASH After Liver Transplantation. Transplantation 2019; 103:57-67. [PMID: 30335694 DOI: 10.1097/tp.0000000000002485] [Citation(s) in RCA: 68] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Nonalcoholic steatohepatitis (NASH) is a growing indication for liver transplant whether the primary or secondary cause of liver disease, and it is expected to be the leading indication in the years to come. Nonalcoholic steatohepatitis recurs after transplant but the impact of the recurrence on allograft and patient outcomes is unclear. A group of multidisciplinary transplant practice providers convened at the International Liver Transplantation Society NASH consensus conference with the purpose of determining the current knowledge and future directions for understanding the recurrence rates, risk and management of NASH in the transplant allograft. Specific questions relating to posttransplant NASH were proposed and reviewed in detail with recommendations on future actions to fill the knowledge gaps.
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Affiliation(s)
- Giacomo Germani
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Marie Laryea
- University of Rochester Medical Center, Rochester NY
| | | | - Hiroto Egawa
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - John OʼGrady
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Kymberly D Watt
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
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9
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Warden BA, Duell PB. Management of dyslipidemia in adult solid organ transplant recipients. J Clin Lipidol 2019; 13:231-245. [PMID: 30928441 DOI: 10.1016/j.jacl.2019.01.011] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2018] [Revised: 01/21/2019] [Accepted: 01/22/2019] [Indexed: 02/07/2023]
Abstract
Solid organ transplantation (SOT) has revolutionized treatment of end-stage disease. Improvements in the SOT continuum of care have unmasked a significant burden of cardiovascular disease, manifesting as a leading cause of morbidity and mortality. Although several risk factors for development of post-transplant cardiovascular disease exist, dyslipidemia remains one of the most frequent and modifiable risks. An important contributor to dyslipidemia in SOT recipients is the off-target metabolic effects of immunosuppressive medications, which may alter lipoproteins and their metabolism. Dyslipidemia management is paramount as lipid-lowering therapy with statins has demonstrated reductions in graft vasculopathy, decreased rejection rates, and improved survival. Several nonstatin medication options are available, but data supporting their benefit in the SOT population are minimal, typically extrapolated from studies in the general population. Further compounding dyslipidemia management is the complex interplay of drug interactions between lipid-lowering and immunosuppressant medications, which can result in serious toxicity and/or therapeutic failure.
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Affiliation(s)
- Bruce A Warden
- Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, USA
| | - P Barton Duell
- Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, USA.
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10
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Naeser V, Brandt AH, Nyhuus B, Borgwardt L, Jørgensen MH, Rasmussen A. Risk markers for later cardiovascular diseases in liver-transplanted children and adolescents. Pediatr Transplant 2018; 22:e13298. [PMID: 30338616 DOI: 10.1111/petr.13298] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2018] [Revised: 08/15/2018] [Accepted: 09/04/2018] [Indexed: 12/25/2022]
Abstract
BACKGROUND Increased risk of cardiovascular diseases is well described after adult liver transplantation, whereas the risk in the pediatric population still is discussed. The aim of this study was to investigate the prevalence of metabolic syndrome in pediatric liver transplant recipients and whether measurements of carotid intima media thickness and pulse wave velocity were increased compared to healthy controls. METHODS We included 42 pediatric liver transplantation recipients and examined them for markers of metabolic syndrome, liver fibrosis measured by shear wave velocity, body fat measured by DXA scans and carotid intima-media thickness, and pulse wave velocity (n = 41 for the carotid scans). The ultrasound measurements of carotid intima-media thickness and pulse wave velocity were also conducted on 82 healthy children and adolescents matched on height and age, respectively. RESULTS Participants had a median age of 13.03 years, and median time since transplantation was 8.54 years. Compared to healthy controls, liver-transplanted patients had significantly increased intima-media thickness measurements in both control groups whereas there was no significant difference with regard to pulse wave velocity. Two patients (6.25%) were diagnosed with metabolic syndrome. Within the group of liver-transplanted pediatric patients, only elevated body mass index was associated with elevated carotid intima-media thickness measurement. Elevated pulse wave velocity was only associated with abdominal obesity. Factors not significantly correlated with either were age, sex, metabolic syndrome, hyperglycemia, triglycerides, years since transplantation, fibrosis of the liver, body fat content, smoking habits, HDL cholesterol levels, hypertension, and mono-drug versus multi-drug therapies. CONCLUSION Pediatric liver transplant recipients do have an increased risk of increased carotid intima-media thickness.
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Affiliation(s)
- Vibeke Naeser
- Department of Surgical Gastroenterology and Transplantation, Rigshospitalet, Copenhagen, Denmark
| | | | - Bo Nyhuus
- Department of Radiology, Rigshospitalet, Copenhagen, Denmark
| | - Lise Borgwardt
- Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet, Copenhagen, Denmark
| | | | - Allan Rasmussen
- Department of Surgical Gastroenterology and Transplantation, Rigshospitalet, Copenhagen, Denmark
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11
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Lower tacrolimus trough levels in the late period after living donor liver transplantation contribute to improvements in long-term clinical outcomes. Hepatobiliary Pancreat Dis Int 2018; 17:204-209. [PMID: 29807766 DOI: 10.1016/j.hbpd.2018.05.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2017] [Accepted: 05/10/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND Previous studies have emphasized the need to reduce tacrolimus (TAC) trough levels in the early post-liver transplantation (LT) period. However, whether late-period TAC trough levels influence the long-term outcomes of liver recipients is not clear. METHODS We enrolled 155 adult liver recipients survived more than 3 years after living donor liver transplantation because of non-malignant liver diseases. The maintenance immunosuppressive regimens were TAC monotherapy and combined therapy with mycophenolate mofetil. Patients were divided into three groups according to their late-period TAC trough levels: < 3 ng/mL group, 3-5 ng/mL group, and >5 ng/mL group. The complications and adverse effects of TAC were analyzed. RESULTS Each group showed similar rejection, graft loss and mortality. Patients achieved the < 5 ng/mL state in less than 4 years had fewer new-onset diabetes, hyperlipidemia, de novo malignancies, and hepatitis B virus recurrence; the complications of renal dysfunction and hypertension rates were the same among these 3 groups. CONCLUSIONS Collectively, our findings indicated that lower TAC trough levels in the late period of liver transplantation are safe, improve the long-term outcomes.
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12
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Abstract
OPINION STATEMENT The long-term survival in liver transplant recipients (LTRs) is currently at an historical high level stemming from improvement in perioperative care, infection control, and immunosuppression medications. However, compared to the general population, LTRs have decreased survival. Metabolic diseases like hypertension, dyslipidemia, type 2 diabetes, and obesity are key determinants of long-term mortality in LTRs. The incidence and prevalence of these metabolic comorbidities is considerably higher in LTRs and likely results from a combination of factors including exposure to chronic immunosuppression, weight gain, and recurrence of chronic liver disease after liver transplantation (LT). Although there is currently little guidance in managing these metabolic conditions post-LT, recommendations are often extrapolated from non-transplant cohorts. In the current review, we explore the relationship between metabolic syndrome and its comorbidities in LTRs.
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13
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Affiliation(s)
- G. Moroni
- Nephrological Unit, Divisione di Nefrologia e Dialisi, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - C. Ponticelli
- Nephrological Unit, Humanitas Clinical and Research Center, Rozzano (Milano), Italy
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14
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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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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: 61] [Impact Index Per Article: 6.8] [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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Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome after Liver Transplant. Int J Mol Sci 2016; 17:490. [PMID: 27049380 PMCID: PMC4848946 DOI: 10.3390/ijms17040490] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2016] [Revised: 03/25/2016] [Accepted: 03/28/2016] [Indexed: 02/07/2023] Open
Abstract
Liver transplant is the unique curative therapy for patients with acute liver failure or end-stage liver disease, with or without hepatocellular carcinoma. Increase of body weight, onset of insulin resistance and drug-induced alterations of metabolism are reported in liver transplant recipients. In this context, post-transplant diabetes mellitus, hyperlipidemia, and arterial hypertension can be often diagnosed. Multifactorial illnesses occurring in the post-transplant period represent significant causes of morbidity and mortality. This is especially true for metabolic syndrome. Non-alcoholic steatosis and steatohepatitis are hepatic manifestations of metabolic syndrome and after liver transplant both recurrent and de novo steatosis can be found. Usually, post-transplant steatosis shows an indolent outcome with few cases of fibrosis progression. However, in the post-transplant setting, both metabolic syndrome and steatosis might play a key role in the stratification of morbidity and mortality risk, being commonly associated with cardiovascular disease. The single components of metabolic syndrome can be treated with targeted drugs while lifestyle intervention is the only reasonable therapeutic approach for transplant patients with non-alcoholic steatosis or steatohepatitis.
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Abstract
BACKGROUND Liver transplantation is a treatment of choice for both acute and chronic liver failure. Accompanied with the increase of long-term survival rates of recipients, metabolic syndrome and its individual components, including obesity, hyperglycemia, hypertension and hyperlipidemia, have become more frequent post liver transplantation. Here we reviewed the literature concerning the risk factors for the development of metabolic complications in liver recipients. DATA SOURCES PubMed was searched for English-language articles published from January 2000 to June 2015. The search criteria focused on risk factors for metabolic syndrome after liver transplantation. RESULT The risk factors of metabolic syndrome in liver recipients include older age, obesity, pre-transplantation diabetes mellitus, hepatitis C virus infection, certain genetic polymorphisms and the use of immunosuppressive drugs. CONCLUSION Active intervention of the risk factors will reduce the occurrence rate of metabolic syndrome after liver transplantation and improve the recipients' quality of life.
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Affiliation(s)
- Jun Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China.
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Hara Y, Kawagishi N, Nakanishi W, Tokodai K, Nakanishi C, Miyagi S, Ohuchi N. Prevalence and risk factors of obesity, hypertension, dyslipidemia and diabetes mellitus before and after adult living donor liver transplantation. Hepatol Res 2015; 45:764-70. [PMID: 25196899 DOI: 10.1111/hepr.12418] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2014] [Revised: 08/30/2014] [Accepted: 09/02/2014] [Indexed: 02/08/2023]
Abstract
AIM The development of metabolic abnormalities after liver transplantation (LTx) contributes to cardiovascular events and mortality. We analyzed the prevalence and risk factors of obesity, hypertension, dyslipidemia and diabetes mellitus (DM) after adult living donor liver transplantation. METHODS Fifty-four adult recipients with a minimum follow up of 6 months receiving living donor liver transplantation between 2001 and 2012 at the Tohoku University Hospital were retrospectively analyzed. RESULTS The prevalence of hypertension increased from 18.5% before transplantation to 35.2% post-transplantation, and new-onset hypertension after transplantation was 57.9% of post-transplant hypertension. Univariate analysis showed that risk factors of post-transplant hypertension were age (>50 years, P = 0.0023), pretransplant body mass index (BMI) of 25 or more (P = 0.0123), pretransplant hypertension (P = 0.0012) and cyclosporin A (61.5% vs tacrolimus 25.0%, P = 0.0248). The incidence of obesity, dyslipidemia and DM did not change from before to after transplantation. LTx was curative in 77.8% of cases of pretransplant dyslipidemia and 20% of cases of pretransplant DM. Primary biliary cirrhosis cases comprised 85.7% of cases of pretransplant dyslipidemia that were cured by LTx. In univariate analysis, pretransplant BMI of 25 or more was the only risk factor of post-transplant dyslipidemia (P = 0.0098). The incidence of new-onset DM after transplantation was 20%. Risk factors of post-transplant DM were male sex (P = 0.0156), pretransplant DM (P < 0.0001), alcohol abuse (P = 0.0248) and mycophenolate mofetil (P = 0.0181) by univariate analysis. CONCLUSION The prevalence of hypertension increased after LTx and pretransplant obesity was associated with several post-transplant metabolic abnormalities.
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Affiliation(s)
- Yasuyuki Hara
- The Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai, Japan
| | - Naoki Kawagishi
- The Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai, Japan
| | - Wataru Nakanishi
- The Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai, Japan
| | - Kazuaki Tokodai
- The Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai, Japan
| | - Chikashi Nakanishi
- The Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai, Japan
| | - Shigehito Miyagi
- The Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai, Japan
| | - Noriaki Ohuchi
- The Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai, Japan
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Ribeiro HDS, Anastácio LR, Ferreira LG, Lagares EB, Lima AS, Correia MITD. Prevalence and factors associated with dyslipidemia after liver transplantation. Rev Assoc Med Bras (1992) 2015; 60:365-72. [PMID: 25211421 DOI: 10.1590/1806-9282.60.04.016] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2013] [Accepted: 01/13/2014] [Indexed: 01/27/2023] Open
Abstract
OBJECTIVE to determine the prevalence of abnormal total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL) and triglycerides in patients undergoing liver transplantation (LTx) and to identify predictors of these disorders. METHODS cross-sectional study to assess the prevalence of dyslipidemia in patients undergoing LTx. Demographic, socioeconomic, clinical, anthropometric and dietetic data were collected to determine the association with dyslipidemia using univariate and multivariate statistical analysis. RESULTS 136 patients were evaluated, 68.1% of which had at least one type of dyslipidemia. The triglyceride level was high in 32.4% of cases, with low HDL in 49.3% of patients and high LDL levels in only 8.8%. High total cholesterol was observed in 16.2% of the study population and was associated with the recommendation for transplantation due to ethanolic cirrhosis (OR = 2.7) and a greater number of hours slept per night (OR = 1.5). CONCLUSION many patients presented dyslipidemia after transplantation, demonstrating the need for interventions in relation to modifiable factors associated with dyslipidemias that can mitigate or prevent these disorders.
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Affiliation(s)
- Hélem de Sena Ribeiro
- Postgraduate Program in Food Science, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil
| | - Lucilene Rezende Anastácio
- Postgraduate Program in Adult Health, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil
| | - Lívia Garcia Ferreira
- Postgraduate Program in Sciences applied to Surgery and Ophthalmology, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil
| | | | - Agnaldo Soares Lima
- Alfa Institute of Gastroenterology, Hospital das Clínicas, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil
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Kallwitz ER. Metabolic syndrome after liver transplantation: Preventable illness or common consequence? World J Gastroenterol 2012; 18:3627-34. [PMID: 22851856 PMCID: PMC3406416 DOI: 10.3748/wjg.v18.i28.3627] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2012] [Revised: 06/25/2012] [Accepted: 06/28/2012] [Indexed: 02/06/2023] Open
Abstract
The metabolic syndrome is common after liver transplant being present in approximately half of recipients. It has been associated with adverse outcomes such as progression of hepatitis C and major vascular events. As the United States population ages and the rate of obesity increases, prevention of the metabolic syndrome in the post-transplant population deserves special consideration. Currently, the metabolic syndrome after transplant appears at least two times more common than observed rates in the general population. Specific guidelines for patients after transplant does not exist, therefore prevention rests upon knowledge of risk factors and the presence of modifiable elements. The current article will focus on risk factors for the development of the metabolic syndrome after transplant, will highlight potentially modifiable factors and propose potential areas for intervention. As in the non-transplant population, behavioral choices might have a major role. Opportunities exist in this regard for health prevention studies incorporating lifestyle changes. Other factors such as the need for immunosuppression, and the changing characteristics of wait listed patients are not modifiable, but are important to know in order to identify persons at higher risk. Although immunosuppression after transplant is unavoidable, the contribution of different agents to the development of components of the metabolic syndrome is also discussed. Ultimately, an increased risk of the metabolic syndrome after transplant is likely unavoidable, however, there are many opportunities to reduce the prevalence.
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Higher tacrolimus blood concentration is related to hyperlipidemia in living donor liver transplantation recipients. Dig Dis Sci 2012; 57:204-9. [PMID: 21743990 DOI: 10.1007/s10620-011-1817-5] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2011] [Accepted: 06/28/2011] [Indexed: 02/05/2023]
Abstract
BACKGROUND The arrival of tacrolimus has drastically improved AALDLT recipients' survival. However, little data of tacrolimus have been reported concerning its effects on lipid metabolism for AALDLT recipients. AIM Out aim was to investigate the relationship between tacrolimus blood concentration and lipid metabolism in AALDLT recipients. METHODS The pre and postoperative data of 77 adult patients receiving AALDLT between 2002 and December 2007 were retrospectively reviewed. The postoperative immune suppressive regimen was prednisone with tacrolimus ± mycophenolate mofetil. Prednisone was withdrawn within the first postoperative month. Blood lipids and tacrolimus concentration were detected at the first, third, and sixth month during follow-up. Episodes of acute rejection were diagnosed based on biopsy. RESULTS Overall prevalence of post-transplantation hyperlipidemia was 29.9% (23/77) at the sixth postoperative month. The patients were divided into two groups, the hyperlipidemia group and the ortholipidemia group. In the 23 patients with hyperlipidemia, 15 (65%) were hypercholesterolemia, five (22%) were hypertriglyceridemia, and three (13%) patients had both hypercholesterolemia and hypertriglyceridemia. In univariate analysis, only tacrolimus blood concentration at the third and sixth post-transplantation months showed significant difference (8.7 ± 2.1 vs. 6.9 ± 3.2, p = 0.013; 9.2 ± 2.7 vs. 7.3 ± 3.8, p = 0.038, respectively). In multivariate logistic analysis, only two factors appear to be risk factors, namely, tacrolimus blood concentration at the third and sixth post-transplantation months (8.7 ± 2.1 vs. 6.9 ± 3.2, p = 0.043; 9.2 ± 2.7 vs. 7.3 ± 3.8 p = 0.035, respectively). CONCLUSIONS Higher tacrolimus blood concentration was related to hyperlipidemia at an early postoperative period. This indicates that tacrolimus blood concentration should be controlled as low as possible in the premise that there is no risk of rejection to minimize post-transplant hyperlipidemia after AALDLT.
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Abstract
Metabolic syndrome (MS) is a cluster of metabolic derangements associated with insulin resistance and an increased risk of cardiovascular mortality. MS has become a major health concern worldwide and is considered to be the etiology of the current epidemic of diabetes and cardiovascular disease. In addition to cardiovascular disease, the presence of MS is also closely associated with other comorbidities including nonalcoholic fatty liver disease (NAFLD). The prevalence of MS in patients with cirrhosis and end-stage liver disease is not well established and difficult to ascertain. Following liver transplant, the prevalence of MS is estimated to be 44-58%. The main factors associated with posttransplant MS are posttransplant diabetes, obesity, dyslipidemia, and hypertension. In addition to developing NAFLD, posttransplant MS is associated with increased cardiovascular mortality that is 2.5 times that of the age- and sex-matched individuals. Additionally, the presence of posttransplant MS has been associated with rapid progression to fibrosis in individuals transplanted for HCV cirrhosis. There is an urgent need for well-designed prospective studies to fully delineate the natural history and risk factors associated with posttransplant MS. Until then, early recognition, prevention, and treatment of its components are vital in improving outcomes in liver transplant recipients.
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Study of the relationship between immunosuppressive therapy and CYP3A4 activity in liver transplantations. EGYPTIAN LIVER JOURNAL 2011. [DOI: 10.1097/01.elx.0000397036.56165.3c] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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Morelli MC, Pinna AD. Trattamento medico a lungo termine del paziente sottoposto a trapianto di fegato. ITALIAN JOURNAL OF MEDICINE 2010. [DOI: 10.1016/j.itjm.2010.07.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
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Pagadala M, Dasarathy S, Eghtesad B, McCullough AJ. Posttransplant metabolic syndrome: an epidemic waiting to happen. Liver Transpl 2009; 15:1662-70. [PMID: 19938136 DOI: 10.1002/lt.21952] [Citation(s) in RCA: 111] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
With increasing survival after orthotopic liver transplantation (OLT), metabolic syndrome and its individual components, including diabetes mellitus, hypertension, dyslipidemia, and obesity, are increasingly being identified and contributing to cardiovascular complications and late morbidity and mortality. The prevalence of posttransplant metabolic syndrome (PTMS) and its individual components has been found to be higher post-OLT versus a comparable population without OLT. The development of nonalcoholic fatty liver disease (NAFLD) after liver transplantation for non-NAFLD cirrhosis is also being increasingly recognized. A number of predictors have been identified as potential risk factors related to these complications. The pretransplant risk factors include immunosuppression, a higher age at transplant, male gender, a history of smoking, the pretransplant body mass index, pre-OLT diabetes, the etiology of the underlying liver disease that resulted in OLT (hepatitis C, cryptogenic cirrhosis, or alcohol), an increased donor body mass index, and marital status. Although there is an increased risk of cardiovascular events, rejection, and infection among patients with PTMS, the overall impact on long-term survival and mortality remains inconclusive. Strategies to reduce the development of metabolic syndrome after transplantation should include lifestyle modifications involving alterations in diet and increased physical activity. Additional measures that may be potentially beneficial include the use of lipid-lowering agents, the optimal control of blood glucose, and the use of tacrolimus instead of cyclosporine.
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Affiliation(s)
- Mangesh Pagadala
- Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
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Beckebaum S, Klein C, Varghese J, Sotiropoulos GC, Saner F, Schmitz K, Gerken G, Paul A, Cicinnati VR. Renal function and cardiovascular risk profile after conversion from ciclosporin to tacrolimus: prospective study in 80 liver transplant recipients. Aliment Pharmacol Ther 2009; 30:834-42. [PMID: 19624550 DOI: 10.1111/j.1365-2036.2009.04099.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Increased risk of cardiovascular and cerebrovascular disease in liver transplant recipients results in particular from the side effects of calcineurin inhibitor-based immunosuppressive therapy. Several studies have demonstrated a more favourable outcome for patients receiving tacrolimus (TAC) as compared with ciclosporin (CS). AIM To investigate the effects of conversion from CS to TAC on cardiovascular risk factors and renal function in liver transplant recipients. METHODS In a prospective study, all except two patients had chronic kidney disease stages 2-4 (n = 80), according to estimated glomerular filtration rate using the abbreviated Modification of Diet in Renal Disease equation. RESULTS Conversion was accompanied with a mean decrease of total cholesterol from 194.6 +/- 54.0 mg/dL to 175.8 +/- 44.2 mg/dL (P < 0.001), low density lipoprotein cholesterol from 106.7 +/- 39.2 mg/dL to 90.9 +/- 28.6 mg/dL (P < 0.001) and mean arterial blood pressure values from 102.2 +/- 13.2 mm Hg to 95.9 +/- 11.7 mm Hg (P < 0.001). Renal function remained stable. No cases of de novo diabetes mellitus were identified. The Framingham risk score was significantly reduced from 5.2 +/- 4.4 at baseline to 4.4 +/- 5.3 after 12 months (P = 0.006). CONCLUSIONS Conversion from CS to TAC has been shown to improve the cardiovascular risk profile and may retard further decline of renal function after liver transplantation.
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Affiliation(s)
- S Beckebaum
- Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany.
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Abstract
In previous decades, pediatric liver transplantation has become a state-of-the-art operation with excellent success and limited mortality. Graft and patient survival have continued to improve as a result of improvements in medical, surgical and anesthetic management, organ availability, immunosuppression, and identification and treatment of postoperative complications. The utilization of split-liver grafts and living-related donors has provided more organs for pediatric patients. Newer immunosuppression regimens, including induction therapy, have had a significant impact on graft and patient survival. Future developments of pediatric liver transplantation will deal with long-term follow-up, with prevention of immunosuppression-related complications and promotion of as normal growth as possible. This review describes the state-of-the-art in pediatric liver transplantation.
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Current concepts in transplant surgery: liver transplantation today. Langenbecks Arch Surg 2008; 393:245-60. [PMID: 18309513 DOI: 10.1007/s00423-007-0262-6] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2007] [Accepted: 12/06/2007] [Indexed: 12/29/2022]
Abstract
INTRODUCTION The discipline of liver transplantation (LTx) has been developed over the past decades, and LTx is now considered the gold standard for the treatment of patients with end-stage liver diseases and early liver tumors in cirrhotic livers. This procedure is now performed routinely in many transplant centers, and it has provided an enormous technical innovation to the field of hepatobiliary surgery. Allocation decision of liver organs is based on medical need and timing. MATERIALS AND METHODS The Mayo Model for End Stage Liver Disease based on patient-specific criteria was developed and applied to prioritize patients on the waiting list. From the donor aspects of LTx, sources of organ, excluding xenotransplantation, can be brain-dead donors, living donors, and non-heart-beating donors. Today, the majority of livers are procured from cadaveric donors. In addition to the conventional LTx, other types are living-donor LTx, reuse of grafts as domino transplantation, ex situ as well as in situ split LTx, and reduced-size LTx. The transplantation procedure consists of several steps including donor selection and management, liver procurement and preservation, back-table preparation, recipient operation with liver implantation, postoperative care, immunosuppression, and follow-up. RESULTS The postoperative complications are divided into surgical, non-surgical, and multifactorial complications. Surgical complications account about 34% of morbidities after LTx and are mainly categorized to vascular and biliary complications. The main medical ones are non-surgical bleeding and infections. The multifactorial complications include primary non- or poor function and small-for-size syndrome. The pretransplant outcome predictors of LTx can be divided into donor, recipient, operative, and postoperative factors. CONCLUSION LTx is now considered a safe and standardized procedure with a substantially improved graft and patient survival and acceptable morbidity rates. However, the new problems, including recurrence of hepatitis C or hepatocellular carcinoma, chronic biliary complications, opportunistic infections, and development of de-novo malignancies are the major problems affecting the long-term outcome of transplanted patients.
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Dehghani SM, Taghavi SAR, Eshraghian A, Gholami S, Imanieh MH, Bordbar MR, Malek-Hosseini SA. Hyperlipidemia in Iranian liver transplant recipients: prevalence and risk factors. J Gastroenterol 2007; 42:769-774. [PMID: 17876547 DOI: 10.1007/s00535-007-2092-2] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2007] [Accepted: 06/27/2007] [Indexed: 02/05/2023]
Abstract
BACKGROUND Hyperlipidemia is a metabolic complication after liver transplantation (LT). The aim of this study was to investigate the prevalence and risk factors for developing hyperlipidemia in patients who underwent LT in the Shiraz Organ Transplantation Center. METHODS Our patients were 170 liver recipients who underwent LT from 1994 to 2006 in the Organ Transplantation Center of the Shiraz University of Medical Sciences. To perform this study we administered questionnaires, including information about age, sex, body mass index (BMI), underlying liver disease, graft type, immunosuppressive medications, and serum levels of triglycerides and cholesterol, before and 6 months after LT. Serum triglyceride and cholesterol levels were considered elevated if they were >150 mg/dl and >250 mg/dl, respectively. Data were analyzed with SPSS software. RESULTS There were 108 male and 62 female patients, with a mean age of 31.4 +/- 13.3 years, and the mean duration of follow-up was 25.9 +/- 23.5 months. The average pretransplant serum triglyceride and cholesterol (mean of individual means) levels were 104.6 +/- 73.2 and 109.5 +/- 51.5 mg/dl, respectively, and the average posttransplant levels were 230.1 +/- 131 and 185 +/- 77 mg/dl, respectively. Six months after LT, 119 (70%) and 26 (15.3%) patients developed hypertriglyceridemia and hypercholesterolemia, respectively. Age, sex, BMI, and underlying liver disease were not predictors of hypertriglyceridemia or hypercholesterolemia (P > 0.05). Posttransplant hypertriglyceridemia was significantly more common in patients receiving tacrolimus than in those receiving cyclosporine (P = 0.040), but posttransplant hypercholesterolemia had no significant correlation with type of immune suppression (P > 0.05). CONCLUSIONS Hyperlipidemia was common after LT, and hypertriglyceridemia was more common than hypercholesterolemia. Among all risk factors, tacrolimus therapy was correlated with development of hypertriglyceridemia after LT.
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Affiliation(s)
- Seyed Mohsen Dehghani
- Organ Transplantation Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
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Wierzbicka A, Pawłowska J, Socha P, Jankowska I, Skorupa E, Teisseyre M, Ismail H, Czubkowski P, Socha J. Lipid, Carbohydrate Metabolism, and Antioxidant Status in Children After Liver Transplantation. Transplant Proc 2007; 39:1523-5. [PMID: 17580179 DOI: 10.1016/j.transproceed.2007.01.084] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2006] [Accepted: 01/29/2007] [Indexed: 11/23/2022]
Abstract
Organ transplantation is a risk factor for atherogenesis that may be related to immunosuppressive therapy. Increased free radical generation may even aggravate atherogenesis. The aim of the study was to assess lipid metabolism in relation to risk factors for atherogenesis as well as carbohydrate metabolism and antioxidant status among children after liver transplantation. We studied 35 children at 3 to 5 years after liver transplant in whom the following parameters were assessed: total cholesterol; triglyceride; high-density lipoprotein cholesterol; low-density lipoprotein cholesterol (LDL-C); very low-density lipoprotein cholesterol; apolipoproteins B, AI, E, lipoprotein (a); vitamin E; glutathione; glucose; insulin; and glutathione peroxidase activity. Three subgroups of patients were assessed according to the immunosuppressive therapy: cyclosporine (CsA), tacrolimus (Tac), or mycophenolate mofetil (MMF) in combination with low-dose CsA or Tac. We observed differences among the subgroups only in total cholesterol (CsA: 131.6 to 285.6; Tac: 144.0 to 181.61; MMF: 132.1 to 181.2) and LDL-C (CsA: 79.4 to 126.9; Tac: 42.2 to 118.8; MMF: 74.2 to 117.3). Lipid metabolism was not significantly disturbed among children after liver transplantation, an observation that does not point to a high risk of atherogenesis. CsA seems to have the strongest untoward effect on cholesterol metabolism. Decreased GSH concentration after liver transplantation may be related to slightly impaired liver function, but GPx activity and vitamin E concentrations remained normal.
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Affiliation(s)
- A Wierzbicka
- Children's Memorial Health Institute, Al. Dzieci Polskich 20, Warsaw, Poland
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Abstract
As survival increases after liver transplantation, common issues that arise involve immunosuppression-related complications and primary health care. Proper emphasis on the prevention and treatment of post-liver transplant complications, such as diabetes mellitus, dyslipidemia, renal dysfunction, osteoporosis, and obesity, requires careful screening and long-term surveillance to minimize the progression of these complications. Active involvement by internists and subspecialists is necessary and a multidisciplinary approach should be undertaken. Liver transplantation should be viewed as a lifelong commitment by both patient and physician.
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Affiliation(s)
- Lawrence U Liu
- Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1104, New York, NY 10029, USA.
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Roy A, Kneteman N, Lilly L, Marotta P, Peltekian K, Scudamore C, Tchervenkov J. Tacrolimus as intervention in the treatment of hyperlipidemia after liver transplant. Transplantation 2006; 82:494-500. [PMID: 16926593 DOI: 10.1097/01.tp.0000231711.82193.41] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND To measure the effect on serum lipids and other risk factors for cardiovascular disease, we converted the primary immunosuppression of dyslipidemic stable liver transplant recipients from cyclosporine A to tacrolimus. METHODS Patients underwent a four-month dietary stabilization period (American Heart Association Step II diet) and serum lipid samples were collected for analysis at a central laboratory. After conversion, dietary counseling and lipid analyses were performed over a six-month postconversion observation period. RESULTS Enrollment was terminated prematurely due to low patient recruitment rates. Thirteen patients were enrolled and provided postconversion data showing surprisingly strong results. At six months postconversion, total cholesterol (C) was reduced by a mean of 0.61 mmol/L (P=0.017), high density lipoprotein cholesterol (HDL-C) remained unchanged; the mean total C:HDL-C ratio was reduced by 0.87 (P=0.001). Low density lipoprotein cholesterol (LDL-C) reductions were not statistically significant, but we observed a significant and persistent decrease in apolipoprotein B (-0.15 g/L six months postconversion, P=0.031). No changes in homocysteine or in vitamins B6 and B12 were discerned, but although red cell folate remained stable, serum folate increased after conversion. We observed no rejection episodes or any other clinically notable events following conversion. CONCLUSIONS In this study, conversion from cyclosporine to tacrolimus provided a safe and well-tolerated alternative that reduced hyperlipidemia and other recognized cardiovascular risk factors.
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Affiliation(s)
- André Roy
- University of Montreal, CHUM-Hopital St-Luc, Montreal, Quebec, Canada.
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Al-Hussaini A, Tredger JM, Dhawan A. Immunosuppression in pediatric liver and intestinal transplantation: a closer look at the arsenal. J Pediatr Gastroenterol Nutr 2005; 41:152-65. [PMID: 16056093 DOI: 10.1097/01.mpg.0000172260.46986.11] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
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Lucey MR, Abdelmalek MF, Gagliardi R, Granger D, Holt C, Kam I, Klintmalm G, Langnas A, Shetty K, Tzakis A, Woodle ES. A comparison of tacrolimus and cyclosporine in liver transplantation: effects on renal function and cardiovascular risk status. Am J Transplant 2005; 5:1111-9. [PMID: 15816894 DOI: 10.1111/j.1600-6143.2005.00808.x] [Citation(s) in RCA: 73] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
A retrospective chart review of 1065 consecutive liver allograft recipients in 11 centers from January 1997 to September 1998 was performed. Patients were followed for 3 years or until graft loss. Patients received either tacrolimus (n = 594), cyclosporine (n = 450) or no calcineurin inhibitor (n = 21). Model for end-stage liver disease (MELD) scores at time of transplant were similar between the two groups. During follow-up, more patients switched from cyclosporine to tacrolimus (26.7%) than from tacrolimus to cyclosporine (12.8%; p < 0.0001). Patient and graft survival were equivalent. Corticosteroid use was more common in cyclosporine-treated patients (p < 0.00001). Patients receiving tacrolimus experienced lower serum creatinine levels at months 3 through 36 (p < 0.0001). Systolic blood pressure was lower in patients receiving tacrolimus (p < 0.001) despite a reduced requirement for anti-hypertensive agents (p < 0.0001). In addition, tacrolimus was associated with lower total cholesterol and triglyceride levels for months 3 through 24 and 3 through 12, respectively (p < 0.01), despite a reduced requirement for anti-hyperlipidemic agents. The incidence of new-onset diabetes mellitus was similar in both groups. While both calcineurin inhibitors were associated with excellent patient and graft survival, renal function, blood pressure and serum lipid levels were significantly better with tacrolimus treatment.
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36
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Abstract
Once regarded as a last-resort therapy for patients with end-stage liver disease, liver transplantation has become a viable therapeutic option because of sweeping improvements in surgical techniques and the development of more powerful immunosuppressive agents. The addition of tacrolimus to the immunosuppression regimen represents a highly potent therapy and a powerful defense against acute rejection. In the decade since tacrolimus was approved for use in the United States, it has become a widely used immunosuppressant in the field of liver transplantation.
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Affiliation(s)
- Ronald W Busuttil
- Division of Liver and Pancreas Transplant, Department of Surgery, UCLA School of Medicine, Los Angeles, CA, USA
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Kirklin JK, Benza RL, Rayburn BK, McGiffin DC. Strategies for minimizing hyperlipidemia after cardiac transplantation. Am J Cardiovasc Drugs 2004; 2:377-87. [PMID: 14727953 DOI: 10.2165/00129784-200202060-00003] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Allograft coronary artery disease represents a major limitation to long-term survival after cardiac transplantation. Hyperlipidemias have been linked to the development of native coronary atherosclerosis, and hyperlipidemic states have correlated with the severity of allograft coronary artery disease. Heart transplant recipients typically manifest increases in plasma levels of total cholesterol, low-density lipoprotein-cholesterol (LDL-C), and triglycerides within the first 3-12 months following transplantation. Factors known to promote post-transplant hyperlipidemia include the use of corticosteroids, cyclosporine (interference with clearance and increased oxidizability of LDL), sirolimus (hypertriglyceridemia), and patient-specific causes of hyperlipidemia which contributed to their underlying heart disease. Hydroxymethylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors are the foundation of antilipid therapy following cardiac transplantation. Pravastatin is effective in lowering plasma cholesterol levels and is associated with a decreased incidence and progression of allograft coronary artery disease. All HMG-CoA reductase inhibitors except pravastatin are metabolized by the hepatic cytochrome P450 system which metabolizes cyclosporine, increasing the risk of myostitis when they are used in large dosages with cyclosporine. Simvastatin, atorvastatin and fluvastatin have been studied in heart transplant recipients. Gemfibrozil has proved effective in transplant recipients when there is isolated marked elevation of plasma triglyceride levels. When hyperlipidemia persists despite therapy, some benefit may result with conversion from cyclosporine to tacrolimus. Although a definitive link between hyperlipidemia and allograft coronary disease has yet to be proven, available evidence points to abnormal lipid metabolism as part of the complex etiologic machinery driving the process of 'chronic rejection'. Consensus exists within the transplant community that a HMG-CoA reductase inhibitor such as pravastatin, should be part of the routine post-transplant drug regimen, and persistent hyperlipidemia should be aggressively treated.
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Affiliation(s)
- James K Kirklin
- Department of Surgery, Division of Cardiothoracic Surgery, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
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38
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Ott R, Bussenius-Kammerer M, Reck T, Koch CA, Kissler H, Hohenberger W, Muller V. Impact of changing immunosuppressive monotherapy from Cyclosporin A to Tacrolimus in long-term, stable liver transplant recipients. Transpl Int 2004. [DOI: 10.1111/j.1432-2277.2004.tb00381.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
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Scott LJ, McKeage K, Keam SJ, Plosker GL. Tacrolimus: a further update of its use in the management of organ transplantation. Drugs 2003; 63:1247-97. [PMID: 12790696 DOI: 10.2165/00003495-200363120-00006] [Citation(s) in RCA: 310] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
UNLABELLED Extensive clinical use has confirmed that tacrolimus (Prograf) is a key option for immunosuppression after transplantation. In large, prospective, randomised, multicentre trials in adults and children receiving solid organ transplants, tacrolimus was at least as effective or provided better efficacy than cyclosporin microemulsion in terms of patient and graft survival, treatment failure rates and the incidence of biopsy-proven acute and corticosteroid-resistant rejection episodes. Notably, the lower incidence of rejection episodes after renal transplantation in tacrolimus recipients was reflected in improved cost effectiveness. In bone marrow transplant (BMT) recipients, the incidence of tacrolimus grade II-IV graft-versus-host disease was significantly lower with tacrolimus than cyclosporin treatment. Efficacy was maintained in renal and liver transplant recipients after total withdrawal of corticosteroid therapy from tacrolimus-based immunosuppression, with the incidence of acute rejection episodes at up to 2 years' follow-up being similar with or without corticosteroids. Tacrolimus provided effective rescue therapy in transplant recipients with persistent acute or chronic allograft rejection or drug-related toxicity associated with cyclosporin treatment. Typically, conversion to tacrolimus reversed rejection episodes and/or improved the tolerability profile, particularly in terms of reduced hyperlipidaemia. In lung transplant recipients with obliterative bronchiolitis, conversion to tacrolimus reduced the decline in and/or improved lung function in terms of forced expiratory volume in 1 second. Tolerability issues may be a factor when choosing a calcineurin inhibitor. Cyclosporin tends to be associated with a higher incidence of significant hypertension, hyperlipidaemia, hirsutism, gingivitis and gum hyperplasia, whereas the incidence of some types of neurotoxicity, disturbances in glucose metabolism, diarrhoea, pruritus and alopecia may be higher with tacrolimus treatment. Renal function, as assessed by serum creatinine levels and glomerular filtration rates, was better in tacrolimus than cyclosporin recipients at up to 5 years' follow-up. CONCLUSION Recent well designed trials have consolidated the place of tacrolimus as an important choice for primary immunosuppression in solid organ transplantation and in BMT. Notably, in adults and children receiving transplants, tacrolimus-based primary immunosuppression was at least as effective or provided better efficacy than cyclosporin microemulsion treatment in terms of patient and graft survival, treatment failure and the incidence of acute and corticosteroid-resistant rejection episodes. The reduced incidence of rejection episodes in renal transplant recipients receiving tacrolimus translated into a better cost effectiveness relative to cyclosporin microemulsion treatment. The optimal immunosuppression regimen is ultimately dependent on balancing such factors as the efficacy of the individual drugs, their tolerability, potential for drug interactions and pharmacoeconomic issues.
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40
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New immunosuppressive strategies in liver transplantation: balancing efficacy and toxicity. Curr Opin Organ Transplant 2003. [DOI: 10.1097/00075200-200306000-00002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
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41
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Abstract
Cardiovascular disease is one of the major causes of morbidity and mortality following solid organ transplantation. Many of the current immunosuppressive drugs are associated with an increase of one or more risk factors for the development of atherosclerosis. This review compares the mechanism by which individual immunosuppressive agents may impact on these risk factors and the differential contribution of cyclosporine, tacrolimus, mycophenolate, azathioprine, and Rapamycin to these individual risk factors. Attention to the potential cardiovascular toxicities of individual immunosuppressive agents may help design strategies for maintenance of immunosuppression tailored to individual patients.
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Affiliation(s)
- Leslie W Miller
- Cardiovascular Division, University of Minnesota, Minneapolis, USA.
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42
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Bostom AD, Brown RS, Chavers BM, Coffman TM, Cosio FG, Culver K, Curtis JJ, Danovitch GM, Everson GT, First MR, Garvey C, Grimm R, Hertz MI, Hricik DE, Hunsicker LG, Ibrahim H, Kasiske BL, Kennedy M, Klag M, Knatterud ME, Kobashigawa J, Lake JR, Light JA, Matas AJ, McDiarmid SV, Miller LW, Payne WD, Rosenson R, Sutherland DER, Tejani A, Textor S, Valantine HA, Wiesner RH. Prevention of post-transplant cardiovascular disease--report and recommendations of an ad hoc group. Am J Transplant 2002; 2:491-500. [PMID: 12118892 DOI: 10.1034/j.1600-6143.2002.20602.x] [Citation(s) in RCA: 65] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Affiliation(s)
- Andrew D Bostom
- Department of Surgery, University of Minnesota, MMC-328 Mayo, Minneapolis 55455, USA
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Rabkin JM, Corless CL, Rosen HR, Olyaei AJ. Immunosuppression impact on long-term cardiovascular complications after liver transplantation. Am J Surg 2002; 183:595-9. [PMID: 12034401 DOI: 10.1016/s0002-9610(02)00826-7] [Citation(s) in RCA: 74] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND With current early transplant patient and allograft survivals nearly optimized, long-term medical complications have become a significant focus for potential improvement in patient outcomes. Cardiovascular disease and associated risk factors have been shown in renal transplant patients to be related to the pharmacologic immunosuppression employed. OBJECTIVE The objective of this study is to investigate at 3 years postliver transplant (OLTx) the incidence of hypertension (HTN), hyperlipidemia (HLIP), diabetes mellitus (DM), nephrotoxicity (NTX), and cardiovascular disease (MI, angioplasty, CHF, CVA, and seborth) as well as rejection in two cohorts of liver transplant recipients who received either tacrolimus (FK-506) or cyclosporine (CSA) and to analyze the consequences of these complications on mortality following transplantation. METHODS Eighty-seven sequential patients (CSA: n = 50, mean age 48 years, M/F 32/18; and FK-506: n = 37, mean age 45 years, M/F 22/15) who underwent OLTx between 1994 and 1998, were >/=18 years, and had a minimum of 3 years of complete follow-up were included in the analysis. All OLTx candidates over age 50, who had a history of alcoholic cirrhosis, or had a history of cardiac conditions/events underwent complete cardiac consultation including an echocardiogram with additional cardiac investigation as indicated prior to OLTx. RESULTS At 3 years following OLTx, the incidence of acute rejection (40% versus 19%, P < 0.05), HTN (62% versus 38%, P < 0.05), HLIP (14% versus 5%, P = 0.08), and cardiovascular disease (18% versus 0%, P < 0.001), were significantly greater for the CSA patients compared with the FK-506 patients. Eight (20%) of the CSA patients who died before 3 years had their death attributed to cardiovascular events versus none in the FK-506 group. CONCLUSION Compared with CSA, FK-506 was associated with significantly less rejection and a reduced incidence of HTN and cardiovascular disease.
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Affiliation(s)
- John M Rabkin
- Department of Surgery, Division of Abdominal Organ Transplantation, Oregon Health Sciences University, 3181 SW Sam Jackson Park Rd. L590, Portland, Oregon 97201-3098, USA.
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44
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Abstract
Liver transplantation has emerged from an experimental therapy to a highly successful treatment for end-stage liver disease. The single most important factor in this progression has been the development of effective immunosuppressive regimens. This article will outline the various immunosuppressive agents used in liver transplantation.
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Affiliation(s)
- Stanley Martin Cohen
- Liver Study Unit, University of Chicago Medical Center, Chicago, Illinois 60637, USA.
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45
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Abstract
1. As long-term survival improves after liver transplantation, cardiovascular complications are emerging as a major cause of late morbidity and mortality. It seems reasonable to correct the potentially reversible cardiovascular risk factors of diabetes, hyperlipidemia, and obesity, in addition to hypertension. 2. The results of liver transplantation in diabetics are acceptable in terms of morbidity, mortality, and prevalence of posttransplant diabetes, but the poor outcomes described in some series suggest that more extensive testing for macro- and microvascular disease may become necessary. 3. The management of diabetes in liver transplant recipients is not substantially different from its management in non-transplant patients, except that steroid reduction or withdrawal and minimizing doses of calcineurin inhibitors are beneficial. 4. Hyperlipidemia occurs in all solid-organ transplantation, with prevalence rates the lowest for liver transplant recipients. Following liver transplantation, between 15% and 40% of recipients on average have increased plasma cholesterol levels and about 40% have hypertriglyceridemia. Dietary changes, weight reduction, exercise and statins are the mainstays of therapy. 5. Retrospective studies suggest that long-term survival of obese recipients after liver transplantation does not differ from nonobese recipients. Posttransplant weight gain occurs in most recipients, and approximately two thirds become overweight. The management of posttransplant obesity is similar to that in non-transplant settings.
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Affiliation(s)
- A Reuben
- Liver Service and Liver Transplant Program, Medical University of South Carolina, Charleston, SC, USA.
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