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Mak LY, Chan AC, Wong TC, Dai WC, She WH, Ma KW, Sin SL, Chu KW, Seto WK, Yuen MF, Lo CM, Fung J. High prevalence of de novo metabolic dysfunction-associated fatty liver disease after liver transplantation and the role of controlled attenuation parameter. BMC Gastroenterol 2023; 23:307. [PMID: 37700227 PMCID: PMC10498589 DOI: 10.1186/s12876-023-02940-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2023] [Accepted: 08/30/2023] [Indexed: 09/14/2023] Open
Abstract
BACKGROUND & AIMS Although non-alcoholic fatty liver disease (NAFLD) remains an uncommon indication for liver transplantation (LT) in the Chinese, the prevalence of NAFLD is increasing. We aimed to determine the prevalence of de novo steatosis and metabolic dysfunction-associated fatty liver disease (MAFLD) after LT. METHODS Transient elastography assessment for liver stiffness and controlled attenuation parameter (CAP) were performed after LT in 549 patients at median time of 77 months from LT. CAP was compared with implant liver biopsy, and also validated in 42 patients with post-LT liver biopsy. Longitudinal history including diabetes mellitus (DM), dyslipidemia, hypertension, and immunosuppressive regimen were recorded. RESULTS The optimal cut-off level of CAP for diagnosing at least mild (≥ S1) and moderate-to-severe steatosis (≥ S2/3) was 266 and 293 dB/m respectively, with AUROC of 0.740 and 0.954 respectively. Using this newly derived cut-off, 28.9% patients have de novo NAFLD, of which 95.6% fulfilled the criteria for MAFLD. After multivariate analysis, BMI (HR 1.34), DM (HR 2.01), hypertension (HR 2.03), HDL-cholesterol (HR 0.25), LDL-cholesterol (HR 1.5) and cryptogenic cirrhosis (HR 4.85) were associated with the development of S2/3 graft steatosis. de novo NAFLD was associated with higher incidence of new-onset hypertension (p < 0.001), graft dysfunction (defined as ALT > 40 U/L; p = 0.008), but not associated with graft fibrosis (defined as liver stiffness > 12 kPa; p = 0.761). CONCLUSION Although NAFLD remains an uncommon primary liver disease indication for LT in Chinese patients, post-transplant de novo graft steatosis is common and the majority is classified as MAFLD. Development of graft steatosis is not associated with an increase in graft fibrosis but was associated with worse metabolic control and graft dysfunction. Routine CAP measurement to detect de novo graft steatosis should be considered after LT regardless of the primary indication of LT.
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Affiliation(s)
- Lung-Yi Mak
- Department of Medicine, The University of Hong Kong Queen Mary Hospital, 102 Pokfulam Road, Pok Fu Lam, Hong Kong
- State Key Laboratory Research of Liver Research, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Albert Cy Chan
- Department of Medicine, The University of Hong Kong Queen Mary Hospital, 102 Pokfulam Road, Pok Fu Lam, Hong Kong
- State Key Laboratory Research of Liver Research, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Tiffany Cl Wong
- Department of Medicine, The University of Hong Kong Queen Mary Hospital, 102 Pokfulam Road, Pok Fu Lam, Hong Kong
- State Key Laboratory Research of Liver Research, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Wing-Chiu Dai
- Department of Medicine, The University of Hong Kong Queen Mary Hospital, 102 Pokfulam Road, Pok Fu Lam, Hong Kong
- State Key Laboratory Research of Liver Research, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Wong-Hoi She
- Department of Medicine, The University of Hong Kong Queen Mary Hospital, 102 Pokfulam Road, Pok Fu Lam, Hong Kong
- State Key Laboratory Research of Liver Research, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Ka-Wing Ma
- Department of Medicine, The University of Hong Kong Queen Mary Hospital, 102 Pokfulam Road, Pok Fu Lam, Hong Kong
- State Key Laboratory Research of Liver Research, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Sui-Ling Sin
- Department of Medicine, The University of Hong Kong Queen Mary Hospital, 102 Pokfulam Road, Pok Fu Lam, Hong Kong
- State Key Laboratory Research of Liver Research, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Ka-Wan Chu
- Department of Medicine, The University of Hong Kong Queen Mary Hospital, 102 Pokfulam Road, Pok Fu Lam, Hong Kong
- State Key Laboratory Research of Liver Research, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Wai-Kay Seto
- Department of Medicine, The University of Hong Kong Queen Mary Hospital, 102 Pokfulam Road, Pok Fu Lam, Hong Kong
- State Key Laboratory Research of Liver Research, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Man-Fung Yuen
- Department of Medicine, The University of Hong Kong Queen Mary Hospital, 102 Pokfulam Road, Pok Fu Lam, Hong Kong
- State Key Laboratory Research of Liver Research, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Chung-Mau Lo
- Department of Medicine, The University of Hong Kong Queen Mary Hospital, 102 Pokfulam Road, Pok Fu Lam, Hong Kong
- State Key Laboratory Research of Liver Research, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - James Fung
- Department of Medicine, The University of Hong Kong Queen Mary Hospital, 102 Pokfulam Road, Pok Fu Lam, Hong Kong.
- State Key Laboratory Research of Liver Research, The University of Hong Kong, Pok Fu Lam, Hong Kong.
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van den Berg EH, Flores-Guerrero JL, Gruppen EG, Garcia E, Connelly MA, de Meijer VE, Bakker SJL, Blokzijl H, Dullaart RPF. Profoundly Disturbed Lipoproteins in Cirrhotic Patients: Role of Lipoprotein-Z, a Hepatotoxic LDL-like Lipoprotein. J Clin Med 2022; 11:jcm11051223. [PMID: 35268313 PMCID: PMC8910943 DOI: 10.3390/jcm11051223] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Revised: 02/20/2022] [Accepted: 02/23/2022] [Indexed: 12/17/2022] Open
Abstract
Detailed information regarding lipoprotein concentrations and subfractions in cirrhotic patients before and after orthotopic liver transplantation (OLT) is lacking. Lipoprotein-Z (LP-Z) is a recently characterised abnormal, hepatotoxic free cholesterol-rich low-density lipoprotein (LDL)-like lipoprotein. We determined the lipoprotein profiles, including LP-Z, in cirrhotic patients and OLT recipients and assessed the prognostic significance of LP-Z on the OLT waiting list. We performed analyses in cirrhotic transplant candidates and non-cirrhotic OLT recipients. A population-based cohort was used as reference. The setting was a University hospital. Lipoprotein particle concentrations and subfractions were measured by nuclear magnetic resonance spectroscopy. In the cirrhotic patients (N = 130), most measures of triglyceride-rich lipoproteins (TRL), LDL, and high-density lipoproteins (HDL) were much lower compared to the OLT recipients (N = 372) and controls (N = 6027) (p < 0.01). In the OLT recipients, many lipoprotein variables were modestly lower, but HDL-cholesterol, triglycerides, and TRL and HDL size were greater vs. the control population. LP-Z was measurable in 40 cirrhotic patients and 3 OLT recipients (30.8% vs. 0.8%, p < 0.001). The cirrhotic patients with measurable LP-Z levels had profoundly lower HDL-cholesterol and particle concentrations (p < 0.001), and worse Child Pugh Turcotte classifications and MELD scores. The presence of LP-Z (adjusted for age, sex, and MELD score) predicted worse survival in cirrhotic patients (HR per 1 LnSD increment: 1.11, 95%CI 1.03−1.19, p = 0.003). In conclusion, cirrhotic patients have considerably lower plasma concentrations of all major lipoprotein classes with changes in lipoprotein subfraction distribution. After OLT, these lipoprotein abnormalities are in part reversed. LP-Z is associated with cirrhosis. Its presence may translate in disturbed HDL metabolism and worse survival.
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Affiliation(s)
- Eline H. van den Berg
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands;
- Correspondence: ; Tel.: +31-50-3610426
| | - Jose L. Flores-Guerrero
- Department of Nephrology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands; (J.L.F.-G.); (E.G.G.); (S.J.L.B.)
| | - Eke G. Gruppen
- Department of Nephrology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands; (J.L.F.-G.); (E.G.G.); (S.J.L.B.)
| | - Erwin Garcia
- Laboratory Corporation of America Holdings (Labcorp), Morrisville, NC 27560, USA; (E.G.); (M.A.C.)
| | - Margery A. Connelly
- Laboratory Corporation of America Holdings (Labcorp), Morrisville, NC 27560, USA; (E.G.); (M.A.C.)
| | - Vincent E. de Meijer
- Department of Hepatopancreatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands;
| | - Stephan J. L. Bakker
- Department of Nephrology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands; (J.L.F.-G.); (E.G.G.); (S.J.L.B.)
| | - Hans Blokzijl
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands;
| | - Robin P. F. Dullaart
- Department of Endocrinology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands;
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3
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Han MAT, Olivo R, Choi CJ, Pyrsopoulos N. De novo and recurrence of metabolic dysfunction-associated fatty liver disease after liver transplantation. World J Hepatol 2021; 13:1991-2004. [PMID: 35070003 PMCID: PMC8727208 DOI: 10.4254/wjh.v13.i12.1991] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 07/27/2021] [Accepted: 11/25/2021] [Indexed: 02/06/2023] Open
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new acronym adopted from the consensus of international experts. Given the increasing prevalence of MAFLD in pre-transplant settings, de novo and recurrent graft steatosis/MAFLD are common in post-transplant settings. The impact of graft steatosis on long-term outcomes is unclear. The current knowledge of incidence rate, risk factors, diagnosis, long-term outcomes, and management of graft steatosis (both de novo and recurrent) is discussed in this review.
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Affiliation(s)
- Ma Ai Thanda Han
- Department of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
| | - Raquel Olivo
- Department of Gastroenterology and Hepatology, Rutgers University, New Jersey Medical School, Newark, NJ 07103, United States
| | - Catherine J Choi
- Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07101, United States
| | - Nikolaos Pyrsopoulos
- Department of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
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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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5
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Abstract
BACKGROUND Posttransplant diabetes mellitus (PTDM) affects up to 50% of solid organ transplant recipients and compromises long-term outcomes. The goal of this study was to investigate how immunosuppressants affect gene expression in a manner that increases diabetes risk, by performing integrative analysis on publicly available, high-throughput gene expression data. METHODS All high-throughput gene expression datasets of solid organ transplant recipients were retrieved from the Gene Expression Omnibus. Significantly dysregulated genes and pathways were determined, and those in common with type 2 diabetes were identified. THP-1 and HepG2 cells were exposed in vitro to tacrolimus, and validation of genes involved in insulin signaling and glucose metabolism was performed using specific arrays. These cells were then treated with the hypoglycemic agents, metformin, and insulin to assess for appropriate reversion of specific diabetogenic genes. RESULTS Insulin signaling and secretion were the most commonly dysregulated pathways that overlapped with diabetes in transplant recipients. KRAS, GRB2, PCK2, BCL2L1, INSL3, DOK3, and PTPN1 were among the most significantly upregulated genes in both immunosuppression and diabetes subsets and were appropriately reverted by metformin as confirmed in vitro. CONCLUSIONS We discovered that the significantly dysregulated genes in the context of immunosuppression are implicated in insulin signaling and insulin secretion, as a manifestation of pancreatic β-cell function. In vitro validation confirmed key diabetes-related genes in the context of immunosuppression. Further analysis and in vitro validation revealed that metformin optimally reverts diabetogenic genes dysregulated in the context of immunosuppression. The optimal therapeutic management of posttransplant diabetes mellitus needs to be further investigated, taking into account the mechanistic impact of immunosuppressants.
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6
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Gadiparthi C, Spatz M, Greenberg S, Iqbal U, Kanna S, Satapathy SK, Broder A, Ahmed A. NAFLD Epidemiology, Emerging Pharmacotherapy, Liver Transplantation Implications and the Trends in the United States. J Clin Transl Hepatol 2020; 8:215-221. [PMID: 32832402 PMCID: PMC7438346 DOI: 10.14218/jcth.2020.00014] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2020] [Revised: 04/15/2020] [Accepted: 05/05/2020] [Indexed: 02/07/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. The spread of obesity worldwide in pandemic proportions has led to a rapid rise of NAFLD in developed and developing countries alike. There are no approved pharmacological agents to treat steatohepatitis or advanced fibrosis but obeticholic acid recently has shown some promise in phase III trial. Currently, NAFLD is the number one etiology for simultaneous liver and kidney transplantation in the USA, second most common indication for liver transplantation (LT) and projected to become number one very soon. LT for NAFLD poses unique challenges, as these patients are generally older, obese and more likely to have a number of metabolic risk factors. Bariatric surgery is an option and can be considered if a structured weight loss program does not achieve the sustained weight loss goal. Comprehensive cardiovascular risk assessment and aggressive management of comorbid conditions are crucial in the LT evaluation process to improve post-transplant survival. Recurrent nonalcoholic steatohepatitis after LT is not uncommon, and thus warrants primary and secondary prevention strategies through a multidisciplinary approach. Prevalence of NAFLD in a donor population is a unique and growing concern that limits the access to quality liver grafts.
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Affiliation(s)
- Chiranjeevi Gadiparthi
- Division of Gastroenterology, Hepatology and Clinical Nutrition, Saint Peter’s University Hospital, New Brunswick, NJ, USA
| | - Moshe Spatz
- Rutgers Robert Wood Johnson Medical School, Piscataway, NJ, USA
| | - Simi Greenberg
- Nova Southeastern University College of Osteopathic Medicine, Davie, FL, USA
| | - Umair Iqbal
- Geisinger Commonwealth School of Medicine, Danville, PA, USA
- Correspondence to: Umair Iqbal, Geisinger Commonwealth School of Medicine, Danville, PA 17822, USA. Tel: +1-607-282-2759, E-mail:
| | - Sowjanya Kanna
- Division of Gastroenterology, Allegheny Health Network, Tarentum, PA, USA
| | - Sanjaya K Satapathy
- Northwell Health, Division of Hepatology & Sandra Atlas Bass Center for Liver Diseases, Manhasset, NY, USA
| | - Arkady Broder
- Division of Gastroenterology, Hepatology and Clinical Nutrition, Saint Peter’s University Hospital, New Brunswick, NJ, USA
| | - Aijaz Ahmed
- Stanford University School of Medicine, Division of Gastroenterology and Hepatology, Stanford, CA, USA
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Millson C, Considine A, Cramp ME, Holt A, Hubscher S, Hutchinson J, Jones K, Leithead J, Masson S, Menon K, Mirza D, Neuberger J, Prasad R, Pratt A, Prentice W, Shepherd L, Simpson K, Thorburn D, Westbrook R, Tripathi D. Adult liver transplantation: UK clinical guideline - part 2: surgery and post-operation. Frontline Gastroenterol 2020; 11:385-396. [PMID: 32879722 PMCID: PMC7447281 DOI: 10.1136/flgastro-2019-101216] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Revised: 09/01/2019] [Accepted: 09/30/2019] [Indexed: 02/06/2023] Open
Abstract
Survival rates for patients following liver transplantation exceed 90% at 12 months and approach 70% at 10 years. Part 1 of this guideline has dealt with all aspects of liver transplantation up to the point of placement on the waiting list. Part 2 explains the organ allocation process, organ donation and organ type and how this influences the choice of recipient. After organ allocation, the transplant surgery and the critical early post-operative period are, of necessity, confined to the liver transplant unit. However, patients will eventually return to their referring secondary care centre with a requirement for ongoing supervision. Part 2 of this guideline concerns three key areas of post liver transplantation care for the non-transplant specialist: (1) overseeing immunosuppression, including interactions and adherence; (2) the transplanted organ and how to initiate investigation of organ dysfunction; and (3) careful oversight of other organ systems, including optimising renal function, cardiovascular health and the psychosocial impact. The crucial significance of this holistic approach becomes more obvious as time passes from the transplant, when patients should expect the responsibility for managing the increasing number of non-liver consequences to lie with primary and secondary care.
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Affiliation(s)
- Charles Millson
- Department of Hepatology, York Teaching Hospitals NHS Foundation Trust, York, UK
| | - Aisling Considine
- Pharmacy department, King's College Hospital NHS Foundation Trust, London, UK
| | - Matthew E Cramp
- South West Liver Unit, Plymouth Hospitals NHS Trust, Plymouth, UK
| | - Andrew Holt
- Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Stefan Hubscher
- Department of Cellular Pathology, University of Birmingham, Birmingham, UK
| | - John Hutchinson
- Department of Hepatology, York Teaching Hospitals NHS Foundation Trust, York, UK
| | - Kate Jones
- Liver Transplantation Service, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Joanna Leithead
- Department of Hepatology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Steven Masson
- Liver Unit, The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Krish Menon
- Liver Transplantation & HPB Surgery, King’s College Hospital NHS Foundation Trust, London, UK
| | - Darius Mirza
- Liver Transplantation & HPB surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - James Neuberger
- Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Raj Prasad
- Liver Transplantation & HPB Surgery, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Anthony Pratt
- Pharmacy Department, York Teaching Hospital NHS Foundation Trust, York, UK
| | - Wendy Prentice
- Palliative Care Medicine, King’s College Hospital NHS Foundation Trust, London, UK
| | - Liz Shepherd
- Liver Transplantation Service, Royal Free London NHS Foundation Trust, London, UK
| | - Ken Simpson
- Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - Doug Thorburn
- Department of Hepatology, Royal Free London NHS Foundation Trust, London, UK
| | - Rachel Westbrook
- Department of Hepatology, Royal Free London NHS Foundation Trust, London, UK
| | - Dhiraj Tripathi
- Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birminghams, UK
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8
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Galvin Z, Rajakumar R, Chen E, Adeyi O, Selzner M, Grant D, Sapisochin G, Greig P, Cattral M, McGilvray I, Ghanekar A, Selzner N, Lilly L, Patel K, Bhat M. Predictors of De Novo Nonalcoholic Fatty Liver Disease After Liver Transplantation and Associated Fibrosis. Liver Transpl 2019; 25:56-67. [PMID: 30609189 DOI: 10.1002/lt.25338] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2018] [Revised: 07/07/2018] [Accepted: 08/05/2018] [Indexed: 12/12/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) can occur de novo in patients undergoing liver transplantation (LT) for indications other than NAFLD, and it has been increasingly recognized as a complication in the post-LT setting. This study aims to better characterize de novo NAFLD after LT by identifying risk factors for its development, describing incidence and extent of fibrosis, assessing the diagnostic utility of noninvasive serum fibrosis algorithms, and comparing survival to those without NAFLD. This was a retrospective single-center analysis of de novo NAFLD in a post-LT cohort. Those whose primary indication for LT was nonalcoholic steatohepatitis (NASH) were excluded. Risk factors were analyzed by univariate and multivariate analyses. De novo NAFLD and fibrosis were assessed on posttransplant liver biopsies, and noninvasive fibrosis scores were calculated from concomitant blood tests. After applying the exclusion criteria, 430 for-cause post-LT biopsies were evaluated; 33.3% (n = 143) had evidence of de novo steatosis and/or NASH at a median of 3.0 years after transplant. On multivariate analysis, body mass index (BMI; odds ratio [OR], 1.12; P < 0.001), diabetes mellitus (OR, 3.01; P = 0.002), hepatitis C virus (OR, 4.61; P < 0.001), weight gain (OR, 1.03; P = 0.007), and sirolimus use (OR, 3.11; P = 0.02) were predictive of de novo NAFLD after LT. Significant fibrosis (≥F2) was present in almost 40% of the cohort. Noninvasive serum fibrosis scores were not useful diagnostic tests. There was no significant difference in the short-term or longterm survival of patients who developed de novo NAFLD. In conclusion, diabetes, BMI, weight gain after LT, and sirolimus-based immunosuppression, in keeping with insulin resistance, were the only modifiable factors associated with development of de novo NAFLD. A significant proportion of patients with de novo NAFLD had fibrosis and given the limited utility of noninvasive serum fibrosis algorithms, alternative noninvasive tools are required to screen for fibrosis in this population. There was no significant difference in the short-term or longterm survival of patients who developed de novo NAFLD.
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Affiliation(s)
- Zita Galvin
- Multi-Organ Transplant Program.,Division of Gastroenterology and Hepatology
| | | | | | - Oyedele Adeyi
- Multi-Organ Transplant Program.,Division of Gastroenterology and Hepatology
| | - Markus Selzner
- Multi-Organ Transplant Program.,Department of Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - David Grant
- Multi-Organ Transplant Program.,Department of Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Gonzalo Sapisochin
- Multi-Organ Transplant Program.,Department of Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Paul Greig
- Multi-Organ Transplant Program.,Department of Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Mark Cattral
- Multi-Organ Transplant Program.,Department of Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Ian McGilvray
- Multi-Organ Transplant Program.,Department of Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Anand Ghanekar
- Multi-Organ Transplant Program.,Department of Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Nazia Selzner
- Multi-Organ Transplant Program.,Division of Gastroenterology and Hepatology
| | - Les Lilly
- Multi-Organ Transplant Program.,Division of Gastroenterology and Hepatology
| | - Keyur Patel
- Multi-Organ Transplant Program.,Division of Gastroenterology and Hepatology
| | - Mamatha Bhat
- Multi-Organ Transplant Program.,Division of Gastroenterology and Hepatology
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9
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Bhat V, Tazari M, Watt KD, Bhat M. New-Onset Diabetes and Preexisting Diabetes Are Associated With Comparable Reduction in Long-Term Survival After Liver Transplant: A Machine Learning Approach. Mayo Clin Proc 2018; 93:1794-1802. [PMID: 30522594 DOI: 10.1016/j.mayocp.2018.06.020] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2018] [Revised: 05/23/2018] [Accepted: 06/05/2018] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To identify key predictors and survival outcomes of new-onset diabetes after transplant (NODAT) in liver transplant (LT) recipients by using the Scientific Registry of Transplant Recipients. PATIENTS AND METHODS Data of all adult LT recipients between October 1, 1987, and March 31, 2016, were analyzed using various machine learning methods. These data were divided into training (70%) and validation (30%) data sets to robustly determine predictors of NODAT. The long-term survival of patients with NODAT relative to transplant recipients with preexisting diabetes and those without diabetes was assessed. RESULTS Increasing age (odds ratio [OR], 1.01; 95% CI, 1.00-1.02; P≤.001), male sex (OR, 1.09; 95% CI, 1.05-1.13; P=.03), and obesity (OR, 1.13; 95% CI, 1.08-1.18; P<.001) were significantly associated with NODAT. Sirolimus as a primary immunosuppressant carried a 33% higher risk of NODAT than did tacrolimus (OR, 1.33; 95% CI, 1.22-1.45; P<.001) at 1 year after LT. Patients with NODAT had significantly decreased 10-year survival than did those without diabetes (63.0% vs 74.9%; P<.001), similar to survival in patients with diabetes before LT (58.9%). CONCLUSION Using a machine learning approach, we found that older, male, and obese recipients are at especially higher risk of NODAT. Donor features do not affect risk. In addition, sirolimus-based immunosuppression is associated with a significantly higher risk of NODAT than other immunosuppressants. Most importantly, NODAT adversely affects long-term survival after LT in a manner similar to preexisting diabetes, indicating the need for more aggressive care and closer follow-up.
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Affiliation(s)
- Venkat Bhat
- Department of Psychiatry, University Health Network, Toronto, Ontario, Canada
| | - Mahmood Tazari
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Kymberly D Watt
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Mamatha Bhat
- Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada; Division of Gastroenterology and Hepatology, University Health Network, Toronto, Ontario, Canada.
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10
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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: 23] [Impact Index Per Article: 2.6] [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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11
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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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Dopazo C, Bilbao I, Castells LL, Sapisochin G, Moreiras C, Campos-Varela I, Echeverri J, Caralt M, Lázaro JL, Charco R. Analysis of adult 20-year survivors after liver transplantation. Hepatol Int 2014; 9:461-70. [PMID: 25788182 PMCID: PMC4473278 DOI: 10.1007/s12072-014-9577-x] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2014] [Accepted: 08/21/2014] [Indexed: 02/07/2023]
Abstract
Background Liver transplantation (LT) is the treatment of choice for chronic and acute liver failure; however, the status of long-term survivors and allograft function is not well known. Aim To evaluate the clinical outcome and allograft function of survivors 20 years post-LT, cause of death during the same period and risk factors of mortality. Methods A retrospective study was conducted from prospective, longitudinal data collected at a single center of adult LT recipients surviving 20 years. A comparative sub-analysis was made with patients who were not alive 20 years post-transplantation to identify the causes of death and risk factors of mortality. Results Between 1988 and 1994, 132 patients received 151 deceased-donors LT and 28 (21 %) survived more than 20 years. Regarding liver function in this group, medians of AST, ALT and total bilirubin at 20 years post-LT were 33 IU/L (13–135 IU/L), 27 (11–152 IU/L) and 0.6 mg/dL (0.3–1.1 mg/dL). Renal dysfunction was observed in 40 % of patients and median eGFR among 20-year survivors was 64 mL/min/1.73 m2 (6–144 mL/min/1.73 m2). Sixty-one percent of 20-year survivors had arterial hypertension, 43 % dyslipidemia, 25 % de novo tumors and 21 % diabetes mellitus. Infections were the main cause of death during the 1st year post-transplant (32 %) and between the 1st and 5th year post-transplant (25 %). After 5th year from transplant, hepatitis C recurrence (22 %) became the first cause of death. Factors having an impact on long-term patient survival were HCC indication (p = 0.049), pre-transplant renal dysfunction (p = 0.043) and long warm ischemia time (p = 0.016); furthermore, post-transplant factors were diabetes mellitus (p = 0.001) and liver dysfunction (p = 0.05) at 1 year. Conclusion Our results showed the effect of immunosuppression used during decades on long-term outcome in our LT patients in terms of morbidity (arterial hypertension, diabetes mellitus, dyslipidemia and renal dysfunction) and mortality (infections and hepatitis C recurrence).
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Affiliation(s)
- C Dopazo
- Department of HBP Surgery and Transplants, Hospital Universitario Vall d´Hebron, Universidad Autónoma de Barcelona, Paseo Vall d´Hebron 119-129, 08035, Barcelona, Spain,
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Bálint A, Farkas K, Szűcs M, Szepes Z, Nagy F, Wittmann T, Molnár T. Long-term increase in serum cholesterol levels in ulcerative colitis patients treated with cyclosporine: an underdiagnosed side effect frequently associated with other drug-related complications. Scand J Gastroenterol 2014; 49:59-65. [PMID: 24138131 DOI: 10.3109/00365521.2013.848231] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION Several serious side effects may limit the use of cyclosporine. Cyclosporine has been reported to increase the total cholesterol level; however, the change in serum cholesterol levels before and after cyclosporine therapy has not been examined in ulcerative colitis (UC) patients. The purpose of this article was to compare serum cholesterol levels before and after cyclosporine therapy in patients with refractory UC and to examine the relationship between serum cholesterol levels and other common side effects. PATIENTS AND METHODS We prospectively assessed serum cholesterol levels in UC patients who had been treated with cyclosporine. Data of 72 patients were analyzed and compared to a control group treated with Infliximab. RESULTS The average duration of cyclosporine therapy was 9.6 months, and side effects developed in 52 patients. Elevated cholesterol levels were detected in 47.2% of the patients. Serum cholesterol levels were significantly increased during and after discontinuation of cyclosporine therapy compared to the time before use of the drug. However, cholesterol levels measured during cyclosporine therapy were significantly higher compared to the time after its discontinuation (p < 0.001). Patients with drug-related side effects showed higher cholesterol levels after discontinuation of the therapy compared to those who did not experience any adverse events. CONCLUSIONS Our findings suggest that cyclosporine therapy may result in increased serum cholesterol levels even in the long-term, after discontinuation of the therapy. Considering that significantly higher post-therapy cholesterol levels were more common in patients who developed drug-related complications, routine measurement of serum cholesterol may increase the safety of the drug.
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Affiliation(s)
- Anita Bálint
- Department I of Medicine, University of Szeged , Szeged , Hungary
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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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McGuire BM, Rosenthal P, Brown CC, Busch AMH, Calcatera SM, Claria RS, Hunt NK, Korenblat KM, Mazariegos GV, Moonka D, Orloff SL, Perry DK, Rosen CB, Scott DL, Sudan DL. Long-term management of the liver transplant patient: recommendations for the primary care doctor. Am J Transplant 2009; 9:1988-2003. [PMID: 19563332 DOI: 10.1111/j.1600-6143.2009.02733.x] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
No official document has been published for primary care physicians regarding the management of liver transplant patients. With no official source of reference, primary care physicians often question their care of these patients. The following guidelines have been approved by the American Society of Transplantation and represent the position of the association. The data presented are based on formal review and analysis of published literature in the field and the clinical experience of the authors. These guidelines address drug interactions and side effects of immunosuppressive agents, allograft dysfunction, renal dysfunction, metabolic disorders, preventive medicine, malignancies, disability and productivity in the workforce, issues specific to pregnancy and sexual function, and pediatric patient concerns. These guidelines are intended to provide a bridge between transplant centers and primary care physicians in the long-term management of the liver transplant patient.
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Affiliation(s)
- B M McGuire
- University of Alabama at Birmingham, Birmingham, AL, USA.
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18
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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; 42:769-74. [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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Guckelberger O, Mutzke F, Glanemann M, Neumann UP, Jonas S, Neuhaus R, Neuhaus P, Langrehr JM. Validation of cardiovascular risk scores in a liver transplant population. Liver Transpl 2006; 12:394-401. [PMID: 16498651 DOI: 10.1002/lt.20722] [Citation(s) in RCA: 54] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Increased prevalence of cardiovascular risk factors has been acknowledged in liver transplant recipients, and an increased incidence of cardiovascular events has been suspected. Individual risk determination, however, has not yet been established. Outpatient charts of 438 primary liver transplants have been reviewed, and suspected cardiovascular risk factors were correlated with cardiovascular events observed during a follow-up period of 10 yr. Receiver operation characteristics curve (ROC) analysis was performed to validate established cardiovascular risk scores. For calibration, the Hosmer-Lemeshow test was performed. A total of 303 of 438 patients were available for risk factor analysis at 6 months and demonstrated complete follow-up data (175 male, 128 female). A total of 40 of those 303 patients experienced fatal or nonfatal cardiovascular events (13.2%). In univariate analysis, age (P < 0.001), gender (P = 0.002), body mass index (P = 0.018), cholesterol (P = 0.044), creatinine (P = 0.006), diabetes mellitus (P = 0.017), glucose (0.006), and systolic blood pressure (P = 0.043), but not cyclosporine A (P = 0.743), tacrolimus (P = 0.870), or steroid medication (P = 0.991), were significantly associated with cardiovascular events. Multivariate analysis, however, identified only age, gender, and cholesterol as independent predictors. In ROC analysis, corresponding areas under the curve for Systematic Coronary Risk Evaluation Project (SCORE), Prospective Cardiovascular Münster Study (PROCAM), and Framingham risk scores (FRSs) were calculated with 0.800, 0.778, and 0.707, respectively. Calibration demonstrated an improved goodness of fit for PROCAM compared to SCORE risk calculations. In conclusion, SCORE and PROCAM proved to be valuable in discriminating our liver transplant recipients for their individual risk of cardiovascular events. Furthermore, calibrated PROCAM risk estimates are required to calculate the number of patients needed to treat in the setup of prospective intervention trials.
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Affiliation(s)
- Olaf Guckelberger
- Department of General, Visceral and Transplantation Surgery, Charité-Campus Vichow-Klinikum, Berlin, Germany.
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Guckelberger O, Byram A, Klupp J, Neumann UP, Glanemann M, Stockmann M, Neuhaus R, Neuhaus P. Coronary event rates in liver transplant recipients reflect the increased prevalence of cardiovascular risk-factors. Transpl Int 2005; 18:967-74. [PMID: 16008748 DOI: 10.1111/j.1432-2277.2005.00174.x] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Increased prevalence of cardiovascular risk-factors in liver transplant recipients compared with pretransplant and standard population data has been acknowledged. The impact of risk-profiles on cardiovascular event rates or death, however, has not yet been established. Here we evaluate the development of risk-factors during a prospective follow-up of 10 years in 302 patients and compare numbers of coronary events with data from the German Prospective Cardiovascular Münster (PROCAM)-Score population. Prevalence of overweight (17% vs. 27%), hypertension (70% vs. 80%), and diabetes (21% vs. 25%) increased from early to late after transplantation, while elevated serum cholesterol (64% vs. 37%) and triglycerides (40% vs. 21%) became less frequent. Cardiovascular risk-profiles favoring tacrolimus over ciclosporin A based immunosuppression early after transplantation converged over time. Increased risk-scores in liver transplant recipients matched with score standardized event rates in the PROCAM population (ratio: 1.11, 95% CI: 0.53-2.03), nine events were predicted for the transplant population and oppose 10 events observed. Thus, indicating a reflection of increased cardiovascular risk-profiles in corresponding numbers of cardiovascular events.
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Affiliation(s)
- Olaf Guckelberger
- Department of General, Visceral and Transplantation Surgery, Charité- Campus Virchow-Klinikum, Berlin, Germany.
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Neal DAJ, Tom BDM, Luan J, Wareham NJ, Gimson AES, Delriviere LD, Byrne CD, Alexander GJM. Is there disparity between risk and incidence of cardiovascular disease after liver transplant? Transplantation 2004; 77:93-9. [PMID: 14724441 DOI: 10.1097/01.tp.0000100685.70064.90] [Citation(s) in RCA: 80] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND Hypertension and hypercholesterolemia are recognized complications of liver transplantation, but whether they contribute to the development of cardiovascular disease is uncertain. We aimed first to determine the prevalence of risk factors for coronary heart disease (CHD) after liver transplantation and second to study the effect of liver transplantation on the predicted 10-year risk of developing CHD and the incidence of cardiovascular events in comparison with a matched local population. METHODS Data on blood pressure, serum lipids, weight, diabetes mellitus, smoking, and incidence of myocardial infarction (MI) and stroke were obtained retrospectively from the case notes of 181 consecutive adult liver transplant recipients (median follow-up 54 months). The Framingham coronary risk equations were used to calculate the 10-year probability of developing CHD. RESULTS The prevalences of hypertension and hypercholesterolemia after transplantation were 77% and 62%, respectively. The predicted 10-year risk of CHD increased from 6.9% before transplantation to 11.5% at 1 year after transplantation, whereas that of a matched local population was 7%. Compared with a matched nontransplant population, the incidence ratios for MI and stroke were 0.55 (95% confidence interval, 0.01-3.06 ) and 1.45 (95% confidence interval, 0.18-5.22), respectively. No patients died from MI or stroke. CONCLUSIONS Liver transplant recipients have a high prevalence of risk factors for cardiovascular disease, exceeding that of the general population, and have a higher predicted risk of developing CHD. Despite this, there were no deaths from CHD or stroke during the study period.
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Affiliation(s)
- David A J Neal
- Department of Medicine, University of Cambridge, School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, UK
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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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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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Charco R, Bilbao I, Chavez R, Castells LI, Hidalgo E, Margarit C. Low incidence of hypercholesterolemia among liver transplant patients under tacrolimus monotherapy immunosuppression. Transplant Proc 2002; 34:1555-6. [PMID: 12176482 DOI: 10.1016/s0041-1345(02)03019-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Affiliation(s)
- R Charco
- Liver Transplantation Unit, Hospital General Universitario Vall d'Hebron, Paseo Vall d'Hebron, 119-129 08035 Barcelona, Spain
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Lladó L, Figueras J, Ramos E, Baliellas C, Torras J, Rafecas A, Fabregat J, Lama C, Ibañez L, Jaurrieta E. Prospective study of a tacrolimus-based quadruple immunosuppressive regimen: evaluation of safety and efficacy. Transplant Proc 2002; 34:1526-8. [PMID: 12176468 DOI: 10.1016/s0041-1345(02)03005-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Affiliation(s)
- L Lladó
- Liver Transplantation Unit, CSU. Bellvitge, c/Feixa Llarga s/n, 09807 Hospitale L1, Barcelona, Spain
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Aguirrezabalaga J, Fernandez-Selles C, Fraguela J, Otero A, Suarez F, Gómez M. Lipid profiles after liver transplantation in patients receiving tacrolimus or cyclosporin. Transplant Proc 2002; 34:1551-2. [PMID: 12176480 DOI: 10.1016/s0041-1345(02)03017-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Affiliation(s)
- J Aguirrezabalaga
- Oficina de Coordinacion de Transplantes, Hospital Juan Canalejo, Xubiaj, 15006 Lacoruna, Spain
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Deters M, Klabunde T, Kirchner G, Resch K, Kaever V. Sirolimus/cyclosporine/tacrolimus interactions on bile flow and biliary excretion of immunosuppressants in a subchronic bile fistula rat model. Br J Pharmacol 2002; 136:604-12. [PMID: 12055139 PMCID: PMC1573383 DOI: 10.1038/sj.bjp.0704756] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
The new immunosuppressive agent sirolimus generally is combined in transplant patients with cyclosporine and tacrolimus which both exhibit cholestatic effects. Nothing is known about possible cholestatic effects of these combinations which might be important for biliary excretion of endogenous compounds as well as of immunosuppressants. Rats were daily treated with sirolimus (1 mg kg(-1) p.o.), cyclosporine (10 mg kg(-1) i.p.), tacrolimus (1 mg kg(-1) i.p.), or a combination of sirolimus with cyclosporine or tacrolimus. After 14 days a bile fistula was installed to investigate the effects of the immunosuppressants and their combinations on bile flow and on biliary excretion of bile salts, cholesterol, and immunosuppressants. Cyclosporine as well as tacrolimus reduced bile flow (-22%; -18%), biliary excretion of bile salts (-15%;-36%) and cholesterol (-15%; -47%). Sirolimus decreased bile flow by 10%, but had no effect on cholesterol or bile salt excretion. Combination of sirolimus/cyclosporine decreased bile flow and biliary bile salt excretion to the same extent as cyclosporine alone, but led to a 2 fold increase of biliary cholesterol excretion. Combination of sirolimus/tacrolimus reduced bile flow only by 7.5% and did not change biliary bile salt and cholesterol excretion. Sirolimus enhanced blood concentrations of cyclosporine (+40%) and tacrolimus (+57%). Sirolimus blood concentration was increased by cyclosporine (+400%), but was not affected by tacrolimus. We conclude that a combination of sirolimus/tacrolimus could be the better alternative to the cotreatment of sirolimus/cyclosporine in cholestatic patients and in those facing difficulties in reaching therapeutic ranges of sirolimus blood concentration.
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Affiliation(s)
- Michael Deters
- Institute of Pharmacology, Medical School of Hannover, 30623 Hannover, Germany.
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&NA;. Lipid abnormalities should be treated in patients with post-transplant hyperlipidaemia associated with calcineurin inhibitors. DRUGS & THERAPY PERSPECTIVES 2002. [DOI: 10.2165/00042310-200218060-00005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
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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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Johnston SD, Morris JK, Cramb R, Gunson BK, Neuberger J. Cardiovascular morbidity and mortality after orthotopic liver transplantation. Transplantation 2002; 73:901-6. [PMID: 11923689 DOI: 10.1097/00007890-200203270-00012] [Citation(s) in RCA: 235] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND Hyperlipidemia and hypertension have been reported in liver allograft recipients and contribute to an increased risk of ischemic heart disease (IHD) after orthotopic liver transplantation (OLT). The aims of the study were (1) to determine the prevalence of risk factors for IHD in these patients and (2) to compare the observed incidence of cardiovascular events and related mortality in allograft recipients with a matched population. METHODS One hundred ten consecutive adults (50 male) who attended for review after OLT (median follow-up 3.9 years; range 0.1-17.9) were assessed for cardiovascular risk factors using current blood pressure, diabetic status, and smoking history and measurements of total cholesterol, high-density lipoprotein cholesterol, and triglyceride concentrations. Cardiovascular events and cardiovascular mortality data were collected from the prospective database of all adult liver allograft recipients and compared to matched data from myocardial infarction registries and Office for National Statistics data, respectively. RESULTS Raised serum cholesterol (>5.0 mmol/L) was found in 48 (44%) patients (18 male), and systolic hypertension (>140 mmHg) was found in 69 (63%) patients (27 male). The relative risk of ischemic cardiac events was 3.07 (95% [confidence interval] CI, 1.98-4.53) and the relative risk for cardiovascular deaths was 2.56 (95% CI, 1.52-4.05) in allograft recipients compared to an age-matched population without transplants. CONCLUSIONS Liver allograft recipients have a greater risk of cardiovascular deaths and ischemic events than an age- and sex-matched population. The prevalence of raised cholesterol concentrations in patients after OLT is similar to those in previous reports. Moderate hypertension and hyperlipidemia may be more detrimental in patients after OLT compared to non-transplant patients without these risk factors.
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Abstract
Cardiovascular disease is now the leading cause of death in transplant recipients. This is due, in part, to the vulnerability of these patients to a complicated set of conditions including hypertension, diabetes mellitus, and post-transplant hyperlipidaemia (PTHL). PTHL is characterised by persistent elevations in total serum cholesterol, low density lipoprotein cholesterol and triglyceride levels. The causes of PTHL are complex and not fully understood, however several classes of immunosuppressants including the corticosteroids, rapamycins and calcineurin inhibitors, appear to play a role. PTHL has been observed in most studies in which patients received calcineurin inhibitor-based regimens, and has been observed with both tacrolimus and cyclosporin. Comparing these calcineurin inhibitors with regard to the relative incidence or severity of PTHL occurring during treatment is difficult because of the use of higher doses of corticosteroids in cyclosporin-based regimens, as compared with tacrolimus-based regimens. However, current expert opinion suggests that the discrepancies in the relative incidence and severity of PTHL are largely accounted for by this difference in corticosteroid dose. At this point in time, evidence for potential differences is scant and inconclusive. Further study is needed, not only to investigate differences in lipid profile, but also of the relative effects of these immunosuppressants on long term graft function as well as on cardiovascular morbidity and mortality. PTHL can be successfully managed with a combination of dietary management, reduction and, if appropriate, withdrawal of corticosteroids, and the administration of lipid-lowering drugs. With this combination of therapeutic options, the threats to long term health posed by PTHL may be effectively addressed.
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Affiliation(s)
- R Moore
- University of Cardiff, Wales, United Kingdom.
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Affiliation(s)
- R Charco
- Liver Transplantation Unit, Hospital General Universitario Vall d'Hebron, Barcelona, Spain
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Lladó L, Figueras J, Ramos E, Lama C, Busquets J, Ibáñez L, Rafecas A, Fabregat J, Torras J, Jaurrieta E. Prospective evaluation of a quadruple therapy based on tacrolimus after liver transplantation. Transplant Proc 2002; 34:108. [PMID: 11959210 DOI: 10.1016/s0041-1345(01)02691-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Affiliation(s)
- L Lladó
- Liver Transplant Unit, C.S.U. Bellvitge, University of Barcelona, Barcelona, Spain
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Lerut J, Ciccarelli O, Mauel E, Gheerardhyn R, Roggen F, Leeuw V, Otte JB, Talpe S, Sempoux C, Laterre PF, Gianello P. Adult liver transplantation and steroidazathioprine withdrawal in cyclosporine (Sandimmun)-based immunosuppression 5 year results of a prospective study. Transpl Int 2001. [DOI: 10.1111/j.1432-2277.2001.tb00081.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Neal DA, Alexander GJ. Can the potential benefits of statins in general medical practice be extrapolated to liver transplantation? Liver Transpl 2001; 7:1009-14. [PMID: 11753902 DOI: 10.1053/jlts.2001.27476] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hypercholesterolemia is a common complication of liver transplantation and is a risk factor for cardiovascular disease after renal and heart transplant. The effect of hyperlipidemia after liver transplantation is less certain, but a less favorable outcome is to be expected. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors or statins have proven efficacy in reducing serum cholesterol and mortality from cardiovascular disease in the general population. Early evidence shows that statins are safe and effective in treating hypercholesterolemia after liver transplantation. Studies in cardiovascular disease have shown that statins exhibit beneficial properties independent of lipid-lowering. These include anti-inflammatory effects and improvement in endothelial function. Recently, statins were shown to repress induction of major histocompatibility complex class II complexes by interferon-gamma, which in turn suppresses activation of T lymphocytes. Such effects may assume significance when using statins after solid-organ transplants. Pravastatin has been shown to reduce acute rejection after cardiac and renal transplantation and to also reduce natural killer cell cytotoxicity in these populations. It remains to be seen whether statins will demonstrate similar benefits after liver transplantation.
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Affiliation(s)
- D A Neal
- Department of Medicine, University of Cambridge, School of Clinical Medicine, Addenbrooke's NHS Trust, Cambridge, UK
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36
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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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Neal DA, Gimson AE, Gibbs P, Alexander GJ. Beneficial effects of converting liver transplant recipients from cyclosporine to tacrolimus on blood pressure, serum lipids, and weight. Liver Transpl 2001; 7:533-9. [PMID: 11443583 DOI: 10.1053/jlts.2001.24637] [Citation(s) in RCA: 69] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hypertension and hyperlipidemia are more prevalent after liver transplantation with cyclosporine as the primary immunosuppressive agent compared with tacrolimus. To determine whether blood pressure, serum lipid level, or weight improves when patients switch immunosuppression therapy, we retrospectively studied 26 liver transplant recipients with stable graft function who had been converted from cyclosporine to tacrolimus therapy with a median follow-up of 8 months. One of the 26 patients developed pruritus necessitating withdrawal of tacrolimus. The results therefore concern the remaining 25 patients. With the exception of a small decrease in bilirubin level (P <.05), there was no difference in graft or renal function after conversion. Mean systolic blood pressure decreased from 158 +/- 25 to 148 +/- 22 mm Hg over a mean of 8 +/- 3 months after conversion to tacrolimus (P =.015), whereas mean serum cholesterol level decreased from 5.3 +/- 0.9 to 4.9 +/- 0.9 mmol/L (P =.01). Sixty-eight percent of the patients lost weight, from a mean of 79.4 +/- 22.6 to 76.1 +/- 20.1 kg, in the 11 months after switching to tacrolimus therapy (P =.024). Serum triglyceride and blood glucose levels did not change, and no patient developed diabetes mellitus after conversion. These results indicate that switching from cyclosporine to tacrolimus can reduce blood pressure, serum cholesterol level, and weight after liver transplantation.
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Affiliation(s)
- D A Neal
- Department of Medicine, University of Cambridge, School of Clinical Medicine, Addenbrooke's NHS Trust, Cambridge, England
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Aguirrezabalaga J, Fernandez-Selles C, Otero A, Suárez F, Gómez M. Lipid profiles in liver transplantation in patients receiving tacrolimus or cyclosporin. Transplant Proc 2001; 33:1064-5. [PMID: 11267192 DOI: 10.1016/s0041-1345(00)02417-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- J Aguirrezabalaga
- Liver Transplantation Unit, Juan Canalejo Medical Center, La Coruña, Spain.
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Manzarbeitia C, Reich DJ, Rothstein KD, Braitman LE, Levin S, Munoz SJ. Tacrolimus conversion improves hyperlipidemic states in stable liver transplant recipients. Liver Transpl 2001; 7:93-9. [PMID: 11172391 DOI: 10.1053/jlts.2001.21289] [Citation(s) in RCA: 45] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
With improvements in surgical technique and the advent of new and more effective immunosuppressive agents, survival rates in liver transplant recipients have dramatically improved. However, hyperlipidemia frequently develops in patients administered cyclosporine-based immunosuppression long-term, although it appears to occur less often with newer, tacrolimus-based regimens. We sought to determine whether an isolated change in the baseline immunosuppressive regimen (cyclosporine to tacrolimus) would improve hyperlipidemic states in these patients. Twenty-one long-term stable liver transplant recipients with hyperlipidemia, manifested by elevated cholesterol and/or triglyceride levels, were offered conversion to tacrolimus from cyclosporine A therapy. Lipid profiles were monitored at baseline (while on cyclosporine therapy) and at 1 and 3 months after conversion to tacrolimus therapy. There were no other medication manipulations. After conversion to tacrolimus therapy, mean cholesterol levels decreased from 251 to 202 mg/dL at 1 month (P <.001) and 194 mg/dL at 3 months (P <.001). Similarly, triglyceride levels decreased from 300 to 207 mg/dL by 1 month (P =.011) and 203 mg/dL by 3 months (P <.001). There was also a statistically significant decrease for very low-density lipoprotein levels at 3 months (P =.005) and low-density lipoprotein levels at 1 and 3 months (P =.013 and P =.014, respectively). High-density lipoprotein levels did not significantly change after conversion to tacrolimus therapy. Conversion was not accompanied by adverse side effects, and patients tolerated the change well. In conclusion, simple conversion from cyclosporine to tacrolimus-based immunosuppression therapy is safe and improves posttransplantation hyperlipidemia in a subgroup of liver transplant recipients.
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Affiliation(s)
- C Manzarbeitia
- Center for Liver Diseases and Liver Transplant Program, Albert Einstein Medical Center, 5401 Old York Rd., Klein #509, Philadelphia, PA 19141, USA.
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Cronin DC, Faust TW, Brady L, Conjeevaram H, Jain S, Gupta P, Millis JM. Modern immunosuppression. Clin Liver Dis 2000; 4:619-55, ix. [PMID: 11232165 DOI: 10.1016/s1089-3261(05)70130-6] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The current treatment of posttransplant lymphoproliferative disease (PTLD) includes prophylaxis at the time of transplant, decreasing or stopping immunosuppresion and initiation of antiviral therapy in patients with polymerase chain reaction or clinical evidence of PTLD, and judicial reintroduction of immunosuppression in patients who have cleared their PTLD and have begun to have rejection. The pharmacology, pharmacokinetics, notable side effects, and toxicities of the immunosuppressive agents are described in this article. At the conclusion of each section the author's current practice with these agents and treatment strategies are described.
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Affiliation(s)
- D C Cronin
- Section of Transplant Surgery, Department of Surgery, University of Chicago, Chicago, Illinois, USA
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